Otenabant HCl | CP-945598 | CAS#686344-29-6 | 686344-29-6 | CB1 antagonist

MedKoo Cat#: 502501 | Name: Otenabant HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Otenabant, also known as CP-945,598, is a drug which acts as a potent and highly selective CB1 antagonist. It was developed by Pfizer for the treatment of obesity, but development for this application has been discontinued following the problems seen during clinical use of the similar drug rimonabant. (source: http://en.wikipedia.org/wiki/Otenabant).

Chemical Structure

Otenabant HCl

CAS#686347-12-6 (HCl)

Theoretical Analysis

MedKoo Cat#: 502501

Name: Otenabant HCl

CAS#: 686347-12-6 (HCl)

Chemical Formula: C25H26Cl3N7O

Exact Mass: 0.0000

Molecular Weight: 546.88

Elemental Analysis: C, 54.91; H, 4.79; Cl, 19.45; N, 17.93; O, 2.93

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship

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Related CAS #

686347-12-6 (HCl) 686344-29-6 (free base)

Synonym

CP945598; CP-945598; CP 945598; CP945,598; CP-945,598; CP 945,598; Otenabant HCl

IUPAC/Chemical Name

1-(8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl)-4-(ethylamino)piperidine-4-carboxamide hydrochloride

InChi Key

KPYUQCJBZGQHPL-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H25Cl2N7O.ClH/c1-2-31-25(24(28)35)11-13-33(14-12-25)22-20-23(30-15-29-22)34(17-9-7-16(26)8-10-17)21(32-20)18-5-3-4-6-19(18)27;/h3-10,15,31H,2,11-14H2,1H3,(H2,28,35);1H

SMILES Code

O=C(C1(NCC)CCN(C2=C3N=C(C4=CC=CC=C4Cl)N(C5=CC=C(Cl)C=C5)C3=NC=N2)CC1)N.[H]Cl

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# Otenabant HCl = CAS#686347-12-6 (HCl). Otenabant free base = CAS#686344-29-6 (free base).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC60728

QC Data

View QC data: current batch, Lot#BBC60728

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Otenabant Hydrochloride is a potent and selective cannabinoid receptor CB1 antagonist with Ki of 0.7 nM.

In vitro activity:

The metabolic turnover of 32 drugs known to be largely metabolized by CYP3A was examined in human liver microsomes (HLMs) from CYP3A5 expressers (*1/*1 genotype) and nonexpressers (*3/*3 genotype) in the presence and absence of ketoconazole and CYP3cide (a selective CYP3A4 inactivator) to calculate the contribution of CYP3A5 to metabolism. Drugs with the highest contribution of CYP3A5 included atazanavir, vincristine, midazolam, vardenafil, otenabant, verapamil, and tacrolimus, whereas 17 of the 32 tested showed negligible CYP3A5 contribution. For otenabant, there is a considerable contribution by CYP3A5 in the *1/*1 donor microsomes, and this contribution is illustrated by the difference in lability between the ketoconazole and CYP3cide-containing incubations. Otenabant had comparable contributions of CYP3A4 and CYP3A5. There were a few drugs for which CYP3A5 was estimated to contribute more than 40% in liver microsomes but for which the ratio of CLint values in recombinant 3A5 and 3A4 was not greater than two (e.g. otenabant). Drug Metabolism and Disposition July 2014, 42 (7) 1163-1173. https://dmd.aspetjournals.org/content/42/7/1163.full?casa_token=0bFzj47rEgAAAAA:ZqAN9CW_qtnEpJnXC8rMFdo5BCm1lhNbavCmN13j5SIe4JPppW-RhqRbkwJ4sOS8Z_YtidNmHEawQg

In vivo activity:

CP-945,598 (1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylamino piperidine-4-carboxylic acid amide hydrochloride) is a recently discovered selective, high affinity, competitive CB1 receptor antagonist that inhibits both basal and cannabinoid agonist-mediated CB1 receptor signaling in vitro and in vivo. CP-945,598 exhibits sub-nanomolar potency at human CB1 receptors in both binding (Ki = 0.7 nM) and functional assays (Ki = 0.2 nM). The compound has low affinity (Ki = 7600 nM) for human CB2 receptors. In vivo, CP-945,598 reverses four cannabinoid agonist-mediated CNS-driven responses (hypo-locomotion, hypothermia, analgesia, and catalepsy) to a synthetic cannabinoid receptor agonist. CP-945,598 exhibits dose and concentrationdependent anorectic activity in two models of acute food intake in rodents, fast-induced re-feeding and spontaneous, nocturnal feeding. CP-945,598 also acutely stimulates energy expenditure in rats and decreases the respiratory quotient indicating a metabolic switch to increased fat oxidation. CP-945,598 at 10 mg/kg promoted a 9%, vehicle adjusted weight loss in a 10 day weight loss study in diet-induced obese mice. Concentration/effect relationships combined with ex vivo brain CB1 receptor occupancy data were used to evaluate efficacy in behavioral, food intake, and energy expenditure studies. Together, these in vitro, ex vivo, and in vivo data indicate that CP-945,598 is a novel CB1 receptor competitive antagonist that may further our understanding of the endocannabinoid system. Biochem Biophys Res Commun. 2010 Apr 2;394(2):366-71. https://www.sciencedirect.com/science/article/abs/pii/S0006291X10004523?via%3Dihub

	Solvent	mg/mL	mM
Solubility
	DMSO	1.0	1.80

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 546.88 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Hadcock JR, Griffith DA, Iredale PA, Carpino PA, Dow RL, Black SC, O'Connor R, Gautreau D, Lizano JS, Ward K, Hargrove DM, Kelly-Sullivan D, Scott DO. In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB(1) receptor antagonist for the management of obesity. Biochem Biophys Res Commun. 2010 Apr 2;394(2):366-71. doi: 10.1016/j.bbrc.2010.03.015. Epub 2010 Mar 6. PMID: 20211605. 2. Tseng E, Walsky RL, Luzietti RA Jr, Harris JJ, Kosa RE, Goosen TC, Zientek MA, Obach RS. Relative contributions of cytochrome CYP3A4 versus CYP3A5 for CYP3A-cleared drugs assessed in vitro using a CYP3A4-selective inactivator (CYP3cide). Drug Metab Dispos. 2014 Jul;42(7):1163-73. doi: 10.1124/dmd.114.057000. Epub 2014 Apr 15. PMID: 24737844. 3. Miao Z, Scott DO, Griffith DA, Day R, Prakash C. Excretion, metabolism, and pharmacokinetics of CP-945,598, a selective cannabinoid receptor antagonist, in rats, mice, and dogs. Drug Metab Dispos. 2011 Dec;39(12):2191-208. doi: 10.1124/dmd.111.040360. Epub 2011 Aug 29. PMID: 21875952. 4.Varga B, Kassai F, Szabó G, Kovács P, Fischer J, Gyertyán I. Pharmacological comparison of traditional and non-traditional cannabinoid receptor 1 blockers in rodent models in vivo. Pharmacol Biochem Behav. 2017 Aug;159:24-35. doi: 10.1016/j.pbb.2017.06.012. Epub 2017 Jun 27. PMID: 28666894

In vitro protocol:

In vivo protocol:

1. Miao Z, Scott DO, Griffith DA, Day R, Prakash C. Excretion, metabolism, and pharmacokinetics of CP-945,598, a selective cannabinoid receptor antagonist, in rats, mice, and dogs. Drug Metab Dispos. 2011 Dec;39(12):2191-208. doi: 10.1124/dmd.111.040360. Epub 2011 Aug 29. PMID: 21875952. 2. Varga B, Kassai F, Szabó G, Kovács P, Fischer J, Gyertyán I. Pharmacological comparison of traditional and non-traditional cannabinoid receptor 1 blockers in rodent models in vivo. Pharmacol Biochem Behav. 2017 Aug;159:24-35. doi: 10.1016/j.pbb.2017.06.012. Epub 2017 Jun 27. PMID: 28666894

1: Miao Z, Sun H, Liras J, Prakash C. Excretion, metabolism, and pharmacokinetics of 1-(8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl)-4-(ethylamino)piperidine- 4-carboxamide, a selective cannabinoid receptor antagonist, in healthy male volunteers. Drug Metab Dispos. 2012 Mar;40(3):568-78. doi: 10.1124/dmd.111.043273. Epub 2011 Dec 20. PubMed PMID: 22187487. 2: Miao Z, Scott DO, Griffith DA, Day R, Prakash C. Excretion, metabolism, and pharmacokinetics of CP-945,598, a selective cannabinoid receptor antagonist, in rats, mice, and dogs. Drug Metab Dispos. 2011 Dec;39(12):2191-208. doi: 10.1124/dmd.111.040360. Epub 2011 Aug 29. PubMed PMID: 21875952. 3: Aronne LJ, Finer N, Hollander PA, England RD, Klioze SS, Chew RD, Fountaine RJ, Powell CM, Obourn JD. Efficacy and safety of CP-945,598, a selective cannabinoid CB1 receptor antagonist, on weight loss and maintenance. Obesity (Silver Spring). 2011 Jul;19(7):1404-14. doi: 10.1038/oby.2010.352. Epub 2011 Feb 3. PubMed PMID: 21293451. 4: Hadcock JR, Griffith DA, Iredale PA, Carpino PA, Dow RL, Black SC, O'Connor R, Gautreau D, Lizano JS, Ward K, Hargrove DM, Kelly-Sullivan D, Scott DO. In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB(1) receptor antagonist for the management of obesity. Biochem Biophys Res Commun. 2010 Apr 2;394(2):366-71. doi: 10.1016/j.bbrc.2010.03.015. Epub 2010 Mar 6. PubMed PMID: 20211605. 5: Griffith DA, Hadcock JR, Black SC, Iredale PA, Carpino PA, DaSilva-Jardine P, Day R, DiBrino J, Dow RL, Landis MS, O'Connor RE, Scott DO. Discovery of 1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4- carboxylic acid amide hydrochloride (CP-945,598), a novel, potent, and selective cannabinoid type 1 receptor antagonist. J Med Chem. 2009 Jan 22;52(2):234-7. doi: 10.1021/jm8012932. PubMed PMID: 19102698. 6: Woods SC. The endocannabinoid system: novel pathway for cardiometabolic Risk-factor reduction. JAAPA. 2007 Nov;Suppl Endocannabinoid:7-10. Review. PubMed PMID: 18047036.