Disodium (2,6-diisopropylphenoxy)methyl phosphate (Fospropofol disodium) [C13H19Na2O5P]

Query Query

Results

Date

3 substances in Reaxys

2018-06-10 19h:39m:50s (UTC)

Na2 + O–

O– P

O O

1. Query

O

Search as: As drawn ))

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Reaxys ID 12826505 View in Reaxys

1/3 O P O

2

Na +

Chemical Name: fospropofol disodium; fospropofol; phosphoric acid mono(2,6-diisopropylphenoxymethyl)ester disodium; Aquavan(R); GPI15715; disodium (2,6-diisopropylphenoxy)methyl phosphate; Ophosphonooxymethyl propofol disodium salt Linear Structure Formula: C13H19O5P(2-)*2Na(1+) Molecular Formula: C13H19O5P*2Na Molecular Weight: 332.244 InChI Key: FVLUXVLPXDIGAK-UHFFFAOYSA-L Note:

O– O–

O

Substance Label (4) Label References 35

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys

Formula I

Patent; Shanxi Synthetic Pharmaceutical Co., Ltd.; Jiangsu Tiandi Renhe Pharmaceutical Co., Ltd.; Zhang Qiyuan; (10 pag.); CN106674270; (2017); (A) Chinese, View in Reaxys

1

Patent; Yichang humanwell pharmaceutical Co., Ltd; Li, Lie; Li, Jie; Fu, Yigang; Wang, Min; Xu, Huabin; Ye, Xia; (15 pag.); CN103172658; (2016); (B) Chinese, View in Reaxys

5, GPI 15715

Kumpulainen, Hanna; Jaervinen, Tomi; Mannila, Anne; Leppaenen, Jukka; Nevalainen, Tapio; Maentylae, Antti; Vepsaelaeinen, Jouko; Rautio, Jarkko; European Journal of Pharmaceutical Sciences; vol. 34; nb. 2-3; (2008); p.

110 - 117, View in Reaxys

Patent-Specific Data (4) References Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys Patent; MGI GP, INC.; WO2007/8869; (2007); (A1) English, View in Reaxys Patent; GUILFORD PHARMACEUTICALS, INC.; WO2006/33911; (2006); (A2) English, View in Reaxys Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys Druglikeness (1) 1 of 1

LogP

2.524

H Bond Donors

0

H Bond Acceptors

4

Rotatable Bonds

6

TPSA

91.46

Lipinski Number

4

Veber Number

2

Density (1) 1 of 1

Measurement Temperature 22.84 [°C] Type (Density)

crystallographic

Location

Paragraph 0034

Patent; Shanxi Synthetic Pharmaceutical Co., Ltd.; Jiangsu Tiandi Renhe Pharmaceutical Co., Ltd.; Zhang Qiyuan; (10 pag.); CN106674270; (2017); (A) Chinese, View in Reaxys Crystal Property Description (1) Colour & Other Location Properties white

supporting informa- Yang, Jun; Yin, Wang; Liu, Jin; Wang, Yu; Zhou, Cheng; Kang, Yi; Zhang, Wen-Sheng; Bition oorganic and Medicinal Chemistry Letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys

Crystal System (1) Crystal System Location Monoclinic

References

Paragraph 0034

References Patent; Shanxi Synthetic Pharmaceutical Co., Ltd.; Jiangsu Tiandi Renhe Pharmaceutical Co., Ltd.; Zhang Qiyuan; (10 pag.); CN106674270; (2017); (A) Chinese, View in Reaxys

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Solubility (MCS) (1) 1 of 1

Location

Page/Page column 2; 4; 5

Comment (Solubility (MCS))

soluble in water

Patent; Yichang humanwell pharmaceutical Co., Ltd; Li, Lie; Li, Jie; Fu, Yigang; Wang, Min; Xu, Huabin; Ye, Xia; (15 pag.); CN103172658; (2016); (B) Chinese, View in Reaxys Space Group (1) Space Group

Location

Comment (Space Group)

References

14

Paragraph 0034

a = 19.755 Å; b = 5.7663 Å; c = 15.425 Å; β = 103.226 °; Z = 4; T = 296 K; Method = X-ray diffraction

Patent; Shanxi Synthetic Pharmaceutical Co., Ltd.; Jiangsu Tiandi Renhe Pharmaceutical Co., Ltd.; Zhang Qiyuan; (10 pag.); CN106674270; (2017); (A) Chinese, View in Reaxys

NMR Spectroscopy (5) 1 of 5

Description (NMR Spectroscopy)

Chemical shifts

Nucleus (NMR Spectroscopy)

1H

Coupling Nuclei

1H

Solvents (NMR Spectroscopy)

water-d2

Temperature (NMR Spectroscopy) [°C]

25

Frequency (NMR Spectro- 300 scopy) [MHz] Location

supporting information

Yang, Jun; Yin, Wang; Liu, Jin; Wang, Yu; Zhou, Cheng; Kang, Yi; Zhang, Wen-Sheng; Bioorganic and Medicinal Chemistry Letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys 2 of 5

Description (NMR Spectroscopy)

Chemical shifts

Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectroscopy)

water-d2

Temperature (NMR Spectroscopy) [°C]

25

Location

supporting information

Yang, Jun; Yin, Wang; Liu, Jin; Wang, Yu; Zhou, Cheng; Kang, Yi; Zhang, Wen-Sheng; Bioorganic and Medicinal Chemistry Letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys 3 of 5

Description (NMR Spectroscopy)

Chemical shifts

Nucleus (NMR Spectroscopy)

1H

Solvents (NMR Spectroscopy)

D2O

Temperature (NMR Spectroscopy) [°C]

25

Frequency (NMR Spectro- 500 scopy) [MHz] Kumpulainen, Hanna; Jaervinen, Tomi; Mannila, Anne; Leppaenen, Jukka; Nevalainen, Tapio; Maentylae, Antti; Vepsaelaeinen, Jouko; Rautio, Jarkko; European Journal of Pharmaceutical Sciences; vol. 34; nb. 2-3; (2008); p. 110 - 117, View in Reaxys

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4 of 5

Description (NMR Spectroscopy)

Chemical shifts

Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectroscopy)

D2O

Temperature (NMR Spectroscopy) [°C]

25

Frequency (NMR Spectro- 125.76 scopy) [MHz] Kumpulainen, Hanna; Jaervinen, Tomi; Mannila, Anne; Leppaenen, Jukka; Nevalainen, Tapio; Maentylae, Antti; Vepsaelaeinen, Jouko; Rautio, Jarkko; European Journal of Pharmaceutical Sciences; vol. 34; nb. 2-3; (2008); p. 110 - 117, View in Reaxys 5 of 5

Description (NMR Spectroscopy)

Chemical shifts

Nucleus (NMR Spectroscopy)

31P

Solvents (NMR Spectroscopy)

D2O

Temperature (NMR Spectroscopy) [°C]

25

Frequency (NMR Spectro- 202.46 scopy) [MHz] Kumpulainen, Hanna; Jaervinen, Tomi; Mannila, Anne; Leppaenen, Jukka; Nevalainen, Tapio; Maentylae, Antti; Vepsaelaeinen, Jouko; Rautio, Jarkko; European Journal of Pharmaceutical Sciences; vol. 34; nb. 2-3; (2008); p. 110 - 117, View in Reaxys IR Spectroscopy (1) 1 of 1

Description (IR Spectroscopy)

Bands; Spectrum

Solvent (IR Spectroscopy)

potassium bromide

Location

Page/Page column 4; 14

Patent; Yichang humanwell pharmaceutical Co., Ltd; Li, Lie; Li, Jie; Fu, Yigang; Wang, Min; Xu, Huabin; Ye, Xia; (15 pag.); CN103172658; (2016); (B) Chinese, View in Reaxys Mass Spectrometry (1) Description (Mass Location Spectrometry) high resolution mass spectrometry (HRMS); spectrum Use (4) Use Pattern

References

supporting informa- Yang, Jun; Yin, Wang; Liu, Jin; Wang, Yu; Zhou, Cheng; Kang, Yi; Zhang, Wen-Sheng; Bition oorganic and Medicinal Chemistry Letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys

Location

References

Pharmaceuticals

Page/Page column title page; 2

Patent; Shanxi Synthetic Pharmaceutical Co., Ltd.; Jiangsu Tiandi Renhe Pharmaceutical Co., Ltd.; Zhang Qiyuan; (10 pag.); CN106674270; (2017); (A) Chinese, View in Reaxys

monitored anesthesia care (MAC) for adult patients

Page/Page column title page; 2

Patent; Shanxi Synthetic Pharmaceutical Co., Ltd.; Jiangsu Tiandi Renhe Pharmaceutical Co., Ltd.; Zhang Qiyuan; (10 pag.); CN106674270; (2017); (A) Chinese, View in Reaxys

Anesthesia

Patent; WINCH, Peter, D.; WO2007/59019; (2007); (A2) English, View in Reaxys

Sedative

Patent; WINCH, Peter, D.; WO2007/59019; (2007); (A2) English, View in Reaxys

Medchem (112) 1 of 112

Substance Effect

Sedative

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

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Bioassay Details

Bioassay : EXAMPLES; [0034] Patients undergoing elective colonoscopy were intravenously administered a 35 mg/mL sterile aqueous solution of 0-phosphonooxymethyl propofol disodium salt for sedation. The patients refrained from ingesting caffeinated drinks and foods or alcohol for at least 12 hours prior to the

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intravenous administration

Qualitative Results

administration of fentanyl citrate (0.5 - 1.5 μg/kg) followed by title compound (7.5 - 12.5 mg/kg) caused concentration-dependent sedative effect; diagram given

Measurement Parameter

qualitative

Patent; MGI GP, INC.; WO2007/8869; (2007); (A1) English, View in Reaxys 2 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : [0080] Venous blood plasma samples taken from the patients of Examples IA and B at several points during and after the procedure were analyzed for concentrations of propofol prodrug and propofol derived from the propofol prodrug, and the obtained values (see Figure 1) were added to a data pool for the

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intravenous administration

Qualitative Results

central volume and clearance of the title compound increased by 1.8% and 1.4%, respectively, per kg of lean body weight over 55 kg; gender and weight were strongly correlated, but there was no independent gender effect; figure

Measurement Parameter

qualitative

Patent; MGI GP, INC.; WO2007/8869; (2007); (A1) English, View in Reaxys 3 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : loss of consciousness; induction of EXAMPLE 1 [50] This example compares the dosedependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intragastric administration

Qualitative Results

title compound at 300-400 mg/kg caused loss of consciousness (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 4 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : loss of consciousness; induction of EXAMPLE 1 [50] This example compares the dosedependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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2018-06-10 19:48:31

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at high doses caused loss of consciousness (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 5 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : pharmacokinetics EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

after administartion of 1-100 mg/kg of title compound Cmax for propofol was 0.00826-5.84 µg/ml and AUCt was 0.389-223 µg x min/ml

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 6 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : pharmacokinetics EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

after administartion of 20-100 mg/kg of title compound Cmax for propofol was 0.0426-0.526 µg/ml and AUCt was 3.70-73.8 µg x min/ml

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 7 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : pharmacokinetics EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

6/38

2018-06-10 19:48:31

Substance Route of Adm.

intravenous administration

Qualitative Results

after administartion of 5 or 50 mg/kg of title compound Cmax for propofol was 0.286 or 2.48 µg/ml and AUCt was 6.94 or 81.8 µg x min/ml

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 8 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : sedation; induction of EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at 100-400 mg/kg caused dose-dependent sedated behavior (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 9 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : sedation; induction of EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at 20-400 mg/kg caused dose-dependent sedative effect within five minutes of administration (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 10 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : sedation; induction of EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at 5-40 mg/kg caused dose-dependent sedated/anesthetized state (figure)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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11 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : pharmacokinetics EXAMPLE 2 [59] In a crossover study aimed at determining the plasma bioavaliablity of propofol after oral or intraduodenal administration of 0-phosphonooxymethyl propofol disodium salt, seven male human volunteers received 400 mg of the test compound dissolved in aqueous solution at a concentration

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

intraduodenal administration

Qualitative Results

0.08-9.0 hours after administartion of 400 mg/kg of title compound appreciable plasma concentrations of propofol were observed

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 12 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : pharmacokinetics EXAMPLE 2 [59] In a crossover study aimed at determining the plasma bioavaliablity of propofol after oral or intraduodenal administration of 0-phosphonooxymethyl propofol disodium salt, seven male human volunteers received 400 mg of the test compound dissolved in aqueous solution at a concentration

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Substance Name

2363920

Substance Route of Adm.

oral administration

Qualitative Results

0.08-9.0 hours after administartion of 400 mg/kg of title compound appreciable plasma concentrations of propofol were observed

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 13 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : loss of consciousness; induction ofBioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intragastric administration

Qualitative Results

title compound at 300-400 mg/kg caused loss of consciousness (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 14 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : loss of consciousness; induction ofBioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxy-

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Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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2018-06-10 19:48:31

methyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at high doses caused loss of consciousness (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 15 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : sedation; induction ofBioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at 100-400 mg/kg caused dose-dependent sedated behavior (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 16 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : sedation; induction ofBioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

title compound at 20-400 mg/kg caused dose-dependent sedative effect within five minutes of administration (figures)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 17 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : sedation; induction ofBioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

9/38

2018-06-10 19:48:31

Substance Route of Adm.

intravenous administration

Qualitative Results

title compound at 5-40 mg/kg caused dose-dependent sedated/anesthetized state (figure)

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 18 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

after administartion of 1-100 mg/kg of title compound Cmax for propofol was 0.00826-5.84 µg/ml and AUCt was 0.389-223 µg x min/ml

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 19 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

after administartion of 20-100 mg/kg of title compound Cmax for propofol was 0.0426-0.526 µg/ml and AUCt was 3.70-73.8 µg x min/ml

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 20 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : EXAMPLE 1 [50] This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, 0-phosphonooxymethyl propofol disodium salt, on rats when administered in a single oral dose to the pharmacological effects observed after an equipotent intravenous infusion. Young adult

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

after administartion of 5 or 50 mg/kg of title compound Cmax for propofol was 0.286 or 2.48 µg/ml and AUCt was 6.94 or 81.8 µg x min/ml

Measurement Parameter

qualitative

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

10/38

2018-06-10 19:48:31

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 21 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : EXAMPLE 2 [59] In a crossover study aimed at determining the plasma bioavaliablity of propofol after oral or intraduodenal administration of 0-phosphonooxymethyl propofol disodium salt, seven male human volunteers received 400 mg of the test compound dissolved in aqueous solution at a concentration

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intraduodenal administration

Qualitative Results

0.08-9.0 hours after administartion of 400 mg/kg of title compound appreciable plasma concentrations of propofol were observed

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 22 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : EXAMPLE 2 [59] In a crossover study aimed at determining the plasma bioavaliablity of propofol after oral or intraduodenal administration of 0-phosphonooxymethyl propofol disodium salt, seven male human volunteers received 400 mg of the test compound dissolved in aqueous solution at a concentration

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

oral administration

Qualitative Results

0.08-9.0 hours after administartion of 400 mg/kg of title compound appreciable plasma concentrations of propofol were observed

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS INC.; WO2005/58250; (2005); (A2) English, View in Reaxys 23 of 112

Substance Effect

Sedative

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Bioassay : This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, O-phosphonooxymethyl propofol disodium salt, on rats when administered in single subcutaneous injections to the pharmacological effects observed after intravenous infusion.

Young adult male Sprague-Dawley

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

subcutaneous administration

Qualitative Results

Title compound innduced a rapid (within 5-10 minutes of dosing) dose-dependent onset of sedated behavior, quickly followed by loss of consciousness in the 100, 200, and 300 mg/kg dose groups; loss of consciousness lasted for more than two hours in animals

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS, INC.; WO2006/33911; (2006); (A2) English, View in Reaxys 24 of 112

Bioassay Category

In Vivo (Animal models)

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11/38

2018-06-10 19:48:31

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, O-phosphonooxymethyl propofol disodium salt, on rats when administered in single subcutaneous injections to the pharmacological effects observed after intravenous infusion. Young adult male Sprague-Dawley

Biological Species/NCBI ID

dog

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

subcutaneous administration

Qualitative Results

after administration of 16 mg/kg propofol parameters: AUC(last) = 1322 h*ng/ml, Cmax = 0.39 &mg;/ml, Tmax = 1.0 h

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS, INC.; WO2006/33911; (2006); (A2) English, View in Reaxys 25 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, O-phosphonooxymethyl propofol disodium salt, on rats when administered in single subcutaneous injections to the pharmacological effects observed after intravenous infusion. Young adult male Sprague-Dawley

Biological Species/NCBI ID

dog

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

intravenous administration

Qualitative Results

after administration of 16 mg/kg propofol parameters: AUC(last) = 1728 h*ng/ml, Cmax = 3.84 &mg;/ml, Tmax = 0.003 h

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS, INC.; WO2006/33911; (2006); (A2) English, View in Reaxys 26 of 112

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : |pharmacokinetics Bioassay : This example compares the dose-dependent pharmacological effects of a propofol prodrug of Formula I, O-phosphonooxymethyl propofol disodium salt, on rats when administered in single subcutaneous injections to the pharmacological effects observed after intravenous infusion. Young adult male Sprague-Dawley

Biological Species/NCBI ID

dog

Substance RN

12826505View in Reaxys

Substance Name

5, GPI 15715

Substance Route of Adm.

rectal administration

Qualitative Results

after administration of 16 mg/kg propofol parameters: AUC(last) = 240.9 h*ng/ml, Cmax = 0.16 &mg;/ml, Tmax = 0.50 h

Measurement Parameter

qualitative

Patent; GUILFORD PHARMACEUTICALS, INC.; WO2006/33911; (2006); (A2) English, View in Reaxys 27 of 112

Bioassay Category

Metabolism/Transport

Bioassay Details

Volume of distribution of compound in human was determined

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

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2018-06-10 19:48:31

Measurement Parameter

Vd (volume of distribution)

Unit

L/kg

Measurement Object

Volume of distribution

Qualitative value

=

Quantitative value

0.11

Gooyit, Major; Lee, Mijoon; Schroeder, Valerie A.; Ikejiri, Masahiro; Suckow, Mark A.; Mobashery, Shahriar; Chang, Mayland; Journal of Medicinal Chemistry; vol. 54; nb. 19; (2011); p. 6676 - 6690, View in Reaxys 28 of 112

Bioassay Category

Metabolism/Transport

Bioassay Details

Volume of distribution of compound in rat was determined

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Measurement Parameter

Vd (volume of distribution)

Unit

L/kg

Measurement Object

Volume of distribution

Qualitative value

=

Quantitative value

0.25

Gooyit, Major; Lee, Mijoon; Schroeder, Valerie A.; Ikejiri, Masahiro; Suckow, Mark A.; Mobashery, Shahriar; Chang, Mayland; Journal of Medicinal Chemistry; vol. 54; nb. 19; (2011); p. 6676 - 6690, View in Reaxys 29 of 112

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

The onset time from the injection of the drug to the disappearance of the righting reflex in rat was measured

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Unit

second

Measurement Object

righting reflex

Qualitative value

=

Quantitative value

2.17

Deviation

0.32

Jun Yang; Wang Yin; Jin Liu; Yu Wang; Cheng Zhou; Yi Kang; Wen-Sheng Zhang; Bioorganic & medicinal chemistry letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys 30 of 112

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Effective dose of the compound required to induce systemic convulsions in rat after administration through the tail vein

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Measurement Parameter

ED50

Unit

mg/kg

Measurement Object

Number of convulsions

Qualitative value

=

Quantitative value

34.78

Deviation

4.14

Jun Yang; Wang Yin; Jin Liu; Yu Wang; Cheng Zhou; Yi Kang; Wen-Sheng Zhang; Bioorganic & medicinal chemistry letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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13/38

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31 of 112

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Lethal dose of the compound against systemic convulsions in rat after compound administration through the tail vein

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Measurement Parameter

LD50

Unit

mg/kg

Measurement Object

PROTECT TYPICAL CONVULSIONS

Qualitative value

=

Quantitative value

163.11

Deviation

19.71

Jun Yang; Wang Yin; Jin Liu; Yu Wang; Cheng Zhou; Yi Kang; Wen-Sheng Zhang; Bioorganic & medicinal chemistry letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys 32 of 112

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

The duration time from the disappearance of the righting reflex to the recovery of the righting reflex in rat

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Measurement Parameter

Activity

Unit

minute

Measurement Object

Dt

Qualitative value

=

Quantitative value

31.04

Deviation

7.9

Jun Yang; Wang Yin; Jin Liu; Yu Wang; Cheng Zhou; Yi Kang; Wen-Sheng Zhang; Bioorganic & medicinal chemistry letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys 33 of 112

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Therapeutic index is ratio of Lethal dose to that of Effective dose required to induce systemic convulsions after compound administration through the tail vein

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Measurement Parameter

qualitative

Measurement Object

Number of convulsions

Qualitative value

Not Published

Jun Yang; Wang Yin; Jin Liu; Yu Wang; Cheng Zhou; Yi Kang; Wen-Sheng Zhang; Bioorganic & medicinal chemistry letters; vol. 23; nb. 6; (2013); p. 1813 - 1816, View in Reaxys 34 of 112

Bioassay Category

Metabolism/Transport

Bioassay Details

Terminal half-life of the compound in human volunteers

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Measurement Parameter

t1/2

Unit

minute

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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14/38

2018-06-10 19:48:31

Qualitative value

=

Quantitative value

46

Fechner, Joerg; Ihmsen, Harald; Hatterscheid, Dirk; Schiessl, Christine; Vornov, James J.; Burak, Eric; Schwilden, Helmut; Schuettler, Juergen; Anesthesiology; vol. 99; nb. 2; (2003); p. 303 - 313, View in Reaxys 35 of 112

Bioassay Category

Metabolism/Transport

Bioassay Details

Central volume of distribution of the compound in human volunteers

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Measurement Parameter

Vd (volume of distribution)

Unit

L/kg

Qualitative value

=

Quantitative value

0.071

Fechner, Joerg; Ihmsen, Harald; Hatterscheid, Dirk; Schiessl, Christine; Vornov, James J.; Burak, Eric; Schwilden, Helmut; Schuettler, Juergen; Anesthesiology; vol. 99; nb. 2; (2003); p. 303 - 313, View in Reaxys 36 of 112

Bioassay Category

Metabolism/Transport

Bioassay Details

Clearance of the compound in human volunteers

Biological Species/NCBI ID

human

Substance RN

12826505View in Reaxys

Unit

mL/min/kg

Qualitative value

=

Quantitative value

7

Fechner, Joerg; Ihmsen, Harald; Hatterscheid, Dirk; Schiessl, Christine; Vornov, James J.; Burak, Eric; Schwilden, Helmut; Schuettler, Juergen; Anesthesiology; vol. 99; nb. 2; (2003); p. 303 - 313, View in Reaxys 37 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

beagle

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

75 mg/kg

Measurement Parameter

time

Unit

minute

Measurement Object

on-set of loss of righting reflex

Quantitative value

2.1

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 38 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

minipig

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

22.5 mg/kg

Measurement Parameter

time

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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15/38

2018-06-10 19:48:31

Unit

minute

Measurement Object

on-set of loss of righting reflex

Quantitative value

1.6

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 39 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

beagle

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

75 mg/kg

Measurement Parameter

time

Unit

minute

Measurement Object

duration of loss righting reflex

Quantitative value

80.4

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 40 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

minipig

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

22.5 mg/kg

Measurement Parameter

time

Unit

minute

Measurement Object

duration of loss righting reflex

Quantitative value

72.6

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 41 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

beagle

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

75 mg/kg

Measurement Parameter

time

Unit

minute

Measurement Object

Total recovery from loss of the righting reflex

Quantitative value

7.3

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 42 of 112

Substance Effect

General Anaesthesic

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

16/38

2018-06-10 19:48:31

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

minipig

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

22.5 mg/kg

Measurement Parameter

time

Unit

minute

Measurement Object

Total recovery from loss of the righting reflex

Quantitative value

6

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 43 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

mouse

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Measurement Parameter

ED50

Unit

mg/kg

Measurement Object

50% animals to loss righting reflex

Quantitative value

94.97

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 44 of 112

Substance Effect

Toxic

Bioassay Category

Toxicity/Safety Pharmacology

Biological Species/NCBI ID

mouse

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

220

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 45 of 112

Substance Effect

General Anaesthesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Measurement Parameter

ED50

Unit

mg/kg

Measurement Object

50% animals to loss righting reflex

Quantitative value

40.98

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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17/38

2018-06-10 19:48:31

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 46 of 112

Substance Effect

Toxic

Bioassay Category

Toxicity/Safety Pharmacology

Biological Species/NCBI ID

rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

189

Qin, Linlin; Ren, Lei; Wan, Songlin; Liu, Guoliang; Luo, Xinfeng; Liu, Zhenhong; Li, Fangqiong; Yu, Yan; Liu, Jianyu; Wei, Yonggang; Journal of Medicinal Chemistry; vol. 60; nb. 9; (2017); p. 3606 - 3617, View in Reaxys 47 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

2.32

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 48 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

2.85

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 49 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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18/38

2018-06-10 19:48:31

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

4.13

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 50 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

4.66

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 51 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

141

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 52 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

22.7

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

19/38

2018-06-10 19:48:31

53 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

47.3

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 54 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

70.5

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 55 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

0.14

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 56 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

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20/38

2018-06-10 19:48:31

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

0.13

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 57 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

0.398

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 58 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

3.95

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 59 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

1.96

Metabolite RN

1866484

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

21/38

2018-06-10 19:48:31

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 60 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

3.74

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 61 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

9.23

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 62 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

16.3

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 63 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

Cmax

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

22/38

2018-06-10 19:48:31

Unit

μg/ml

Quantitative value

0.17

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 64 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

0.23

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 65 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

0.044

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 66 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

0.05

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 67 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

23/38

2018-06-10 19:48:31

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

3.15

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 68 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

0.644

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 69 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

2.16

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 70 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.21

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 71 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

24/38

2018-06-10 19:48:31

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.23

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 72 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.49

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 73 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.19

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 74 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.49

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 75 of 112

Bioassay Category

Pharmacokinetic

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

25/38

2018-06-10 19:48:31

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

Vd (volume of distribution)

Unit

l/kg

Quantitative value

1.02

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 76 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

CL (drug clearance)

Unit

l/h/kg

Quantitative value

1.38

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 77 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

0.264

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 78 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

0.448

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

26/38

2018-06-10 19:48:31

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 79 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

1.03

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 80 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

3.46

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 81 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

0.05

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 82 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-inf)

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

27/38

2018-06-10 19:48:31

Unit

μg*h/ml

Quantitative value

0.06

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 83 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

3.15

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 84 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

0.65

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 85 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-inf)

Unit

μg*h/ml

Quantitative value

2.18

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 86 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

28/38

2018-06-10 19:48:31

Substance Route of Adm.

oral administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

0.04

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 87 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

0.53

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 88 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

5.84

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 89 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

1.27

Metabolite RN

1866484

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

29/38

2018-06-10 19:48:31

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 90 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

Cmax

Unit

μg/ml

Quantitative value

0.29

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 91 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

5 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

0.12

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 92 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

20 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

0.06

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 93 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

30/38

2018-06-10 19:48:31

Substance Dose

30 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

0.353

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 94 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

1.21

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 95 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

AUC (0-6 h)

Unit

μg*h/ml

Quantitative value

3.57

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 96 of 112

Substance Effect

Sedative

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

10 - 40 mg/kg

Substance Route of Adm.

intravenous drug administration

Measurement Parameter

% increase

Qualitative value

Active

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

31/38

2018-06-10 19:48:31

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 97 of 112

Substance Effect

Sedative

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 - 200 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

% increase

Qualitative value

Moderate

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 98 of 112

Substance Effect

Sedative

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

300 - 400 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

qualitative

Measurement Object

Loss of consciousness

Qualitative value

Active

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 99 of 112

Substance Effect

Sedative

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

100 - 400 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Measurement Parameter

qualitative

Measurement Object

Loss of consciousness

Qualitative value

Active

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 100 of 112

Substance Effect

Analgesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

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Substance Dose

75 - 100 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

% decrease

Measurement Object

withdrawal latency, thermal hyperalgesia at hindpaw

Qualitative value

Active

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 101 of 112

Substance Effect

Analgesic

Bioassay Category

In Vivo (Animal models)

Biological Species/NCBI ID

Sprague Dawley rat

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

50 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

% decrease

Measurement Object

withdrawal latency, thermal hyperalgesia at hindpaw

Qualitative value

Not active

Measurement pX

1

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 102 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

oral administration

Substance Dosing Regimen

Single

Measurement Parameter

tmax

Unit

h

Quantitative value

0.08

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 103 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Substance Dosing Regimen

Single

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Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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Measurement Parameter

tmax

Unit

h

Quantitative value

0.17

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 104 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Substance Dosing Regimen

Single

Measurement Parameter

tmax

Unit

h

Quantitative value

0.17

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 105 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

oral administration

Substance Dosing Regimen

Single

Measurement Parameter

tmax

Unit

h

Quantitative value

0.33

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 106 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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Substance Dosing Regimen

Single

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.28

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 107 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

intravenous drug administration

Substance Dosing Regimen

Single

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.28

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 108 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

oral administration

Substance Dosing Regimen

Single

Measurement Parameter

t1/2 el

Unit

h

Quantitative value

0.32

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 109 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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Substance Dosing Regimen

Single

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

0.1

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 110 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

oral administration

Substance Dosing Regimen

Single

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

1

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 111 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

oral administration

Substance Dosing Regimen

Single

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

30

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys 112 of 112

Bioassay Category

Pharmacokinetic

Biological Species/NCBI ID

human

Population State

Healthy

Substance RN

12826505View in Reaxys

Substance Name

fospropofol disodium

Substance Dose

400 mg/kg

Substance Route of Adm.

intraduodenal drug administration

Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only.

Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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Substance Dosing Regimen

Single

Measurement Parameter

F (drug bioavailability)

Unit

%

Quantitative value

37

Metabolite RN

1866484

Patent; THE JOHNS HOPKINS UNIVERSITY; SLUSHER, Barbara; RAIS, Rana; VORNOV, James; (78 pag.); WO2017/205632; (2017); (A1) English, View in Reaxys

Reaxys ID 25844484 View in Reaxys

2/3 O–

Linear Structure Formula: C13H19O5P(2-)*Na(1+) Molecular Formula: C13H19O5P*Na Molecular Weight: 309.254 InChI Key: FVLUXVLPXDIGAK-UHFFFAOYSA-L Note:

O– P O O Na +

O

Druglikeness (1) 1 of 1

LogP

2.524

H Bond Donors

0

H Bond Acceptors

4

Rotatable Bonds

6

TPSA

91.46

Lipinski Number

4

Veber Number

2

Bioassay Category

Pharmacokinetic

Bioassay Details

In vivo time taken to reach maximum plasma concentration of compound in rat after intavenous administration of dose at 40 mg/kg

Biological Species/NCBI ID

rat

Substance RN

25844484View in Reaxys

Substance Route of Adm.

intravenous administration

Measurement Parameter

tmax

Unit

minute

Measurement Object

Tmax

Qualitative value

=

Quantitative value

3.7

Deviation

0.2

Medchem (2) 1 of 2

Kumpulainen, Hanna; Jaervinen, Tomi; Mannila, Anne; Leppaenen, Jukka; Nevalainen, Tapio; Maentylae, Antti; Vepsaelaeinen, Jouko; Rautio, Jarkko; European Journal of Pharmaceutical Sciences; vol. 34; nb. 2-3; (2008); p. 110 - 117, View in Reaxys 2 of 2

Bioassay Category

Pharmacokinetic

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Bioassay Details

In vivo maximum plasma concentration of compound in rat after intavenous administration of dose at 40 mg/kg

Biological Species/NCBI ID

rat

Substance RN

25844484View in Reaxys

Substance Route of Adm.

intravenous administration

Measurement Parameter

Cmax

Unit

µg/mL

Measurement Object

Maximum plasma concentration of compound in rat

Qualitative value

=

Quantitative value

7.1

Deviation

1.6

Kumpulainen, Hanna; Jaervinen, Tomi; Mannila, Anne; Leppaenen, Jukka; Nevalainen, Tapio; Maentylae, Antti; Vepsaelaeinen, Jouko; Rautio, Jarkko; European Journal of Pharmaceutical Sciences; vol. 34; nb. 2-3; (2008); p. 110 - 117, View in Reaxys

Reaxys ID 29966792 View in Reaxys 2

Na +

-1

3/3

H 2O

O–

O–

Linear Structure Formula: C13H19O5P(2-)*2Na(1+)*xH2O Molecular Formula: C13H19O5P*(x)H2O*2Na InChI Key: PSFIXYJJRKTRHC-UHFFFAOYSA-L Note:

P O

O

O

Substance Label (1) Label References 2

Patent; Yichang humanwell pharmaceutical Co., Ltd; Li, Lie; Li, Jie; Fu, Yigang; Wang, Min; Xu, Huabin; Ye, Xia; (15 pag.); CN103172658; (2016); (B) Chinese, View in Reaxys

Druglikeness (1) 1 of 1

LogP

2.057

H Bond Donors

1

H Bond Acceptors

5

Rotatable Bonds

6

TPSA

91.46

Lipinski Number

4

Veber Number

2

Crystal Phase (1) Description (Crystal Phase) Interplanar spacing Space Group (1) Location Page/Page column 2; 4; 8; 9

Location

References

Page/Page column 2; 4; 8; 9

Patent; Yichang humanwell pharmaceutical Co., Ltd; Li, Lie; Li, Jie; Fu, Yigang; Wang, Min; Xu, Huabin; Ye, Xia; (15 pag.); CN103172658; (2016); (B) Chinese, View in Reaxys

Comment (Space Group)

References

Method = Powder X-ray diffraction

Patent; Yichang humanwell pharmaceutical Co., Ltd; Li, Lie; Li, Jie; Fu, Yigang; Wang, Min; Xu, Huabin; Ye, Xia; (15 pag.); CN103172658; (2016); (B) Chinese, View in Reaxys

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Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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