OTENABANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H25Cl2N7O
Molecular Weight	510.418
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC1(CCN(CC1)C2=NC=NC3=C2N=C(N3C4=CC=C(Cl)C=C4)C5=CC=CC=C5Cl)C(N)=O

InChI

InChIKey=UNAZAADNBYXMIV-UHFFFAOYSA-N

InChI=1S/C25H25Cl2N7O/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)

HIDE SMILES / InChI

Description
Sources: https://ncats.nih.gov/files/CP-945598.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=20211605 | https://www.ncbi.nlm.nih.gov/pubmed/?term=19102698

Otenabant (CP-945,598) is Pfizer developed as a potent and selective cannabinoid receptor CB1 antagonist with Ki of 0.7 nM, which exhibits 10,000-fold greater selectivity against human CB2 receptor, for treatment of obesity. In clinical trial III Pfizer decided to discontinue the development program based on changing regulatory perspectives on the risk/benefit profile of the CB1 class and likely new regulatory requirements for approval.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cannabinoid CB1 receptor 85 Target ID: CHEMBL218 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19102698	Antagonist 2778		0.7 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20211605	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
14 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22187487	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		OTENABANT serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
42 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22187487	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		N-DESETHYL OTENABANT serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
0.01 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22187487	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		OTENABANT serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3966 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22187487	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		N-DESETHYL OTENABANT serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
159 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22187487	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		OTENABANT serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
139 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22187487	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		N-DESETHYL OTENABANT serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767 substrate 1037	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991 CYP3A5 395 CYP1A1 349 CYP2E1 667 CYP1A2 1054 CYP2C8 693 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677769	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677769	yes [IC50 16.933 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677769	yes [IC50 2.1317 uM]

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24737844/	major
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24737844/	major
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22187487/	no
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677769	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/19102698/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003PJF	https://www.1pchem.com/search?query=1P003PJF
1PlusChem LLC	1P00FCHE	https://www.1pchem.com/search?query=1P00FCHE
AK Scientific	Y0367	https://aksci.com/item_detail.php?cat=Y0367
AK Scientific	Y0444	https://aksci.com/item_detail.php?cat=Y0444
AbovChem LLC	HY-10871A	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-10871A
Angene	AGN-PC-0TTAJZ	http://www.angenechemical.com/productshow/AGN-PC-0TTAJZ.html
ApexBio Technology	A1435	https://www.apexbt.com/catalogsearch/result/?q=A1435
ApexBio Technology	A3691	https://www.apexbt.com/catalogsearch/result/?q=A3691
AstaTech	40656	http://astatechinc.com/CPSResult.php?CRNO=40656
AstaTech	40657	http://astatechinc.com/CPSResult.php?CRNO=40657
Axon MedChem	2015	https://www.axonmedchem.com/product/2015
Axon MedChem	2119	https://www.axonmedchem.com/product/2119
BLD Pharm	BD395940	http://www.bldpharm.com/search/Search.html?keyword=BD395940
BLD Pharm	BD630826	http://www.bldpharm.com/search/Search.html?keyword=BD630826
BOC Sciences	686344-29-6	http://www.bocsci.com/description.asp?cas=686344-29-6
Cayman Chemical	11955	http://www.caymanchem.com/app/template/Product.vm/catalog/11955
Chem Scene	CS-1279	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1279
ChemShuttle	111938	https://www.chemshuttle.com/catalogsearch/result/?q=111938
ChemShuttle	169481	https://www.chemshuttle.com/catalogsearch/result/?q=169481
Debye Scientific	DA-41691	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-41691
Debye Scientific	DA-41692	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-41692
Excenen	EX-A142	http://www.excenen.com/searchresultlist.php?id=EX-A142
Excenen	EX-A466	http://www.excenen.com/searchresultlist.php?id=EX-A466
KeyOrganics	AS-56103	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56103
KeyOrganics	AS-57939	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-57939
Matrix Scientific	147265	http://www.matrixscientific.com/147265.html
MedChem Express	HY-10871	https://www.medchemexpress.com/search.html?q=HY-10871&ft=&fa=&fp=
MolPort	MolPort-023-277-113	https://www.molport.com/shop/molecule-link/MolPort-023-277-113
MolPort	MolPort-035-706-579	https://www.molport.com/shop/molecule-link/MolPort-035-706-579
Molnova	M15622	https://www.molnova.com/en/serch-list.html?keywords=M15622
MuseChem	I008513	https://www.musechem.com/product/I008513.html
MuseChem	I008514	https://www.musechem.com/product/I008514.html
Ryan Scientific	ELN_441958	https://ryansci.com/products?q=ELN_441958&list_q=&search_type=exact
Selleck Chemicals	S8012	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8012
ShangHai Biochempartner	BCP06883	http://www.biochempartner.com/search_BCP06883
ShangHai Biochempartner	BCP07507	http://www.biochempartner.com/search_BCP07507
TargetMol	T1796	https://www.targetmol.com/search?keyword=T1796
TargetMol	T3530	https://www.targetmol.com/search?keyword=T3530
Tocris	4236	https://www.tocris.com/search.php?Type=QuickSearch&Value=4236
Toronto Research Chemicals	C781410	https://www.trc-canada.com/product-detail/?CatNum=C781410
Toronto Research Chemicals	C781420	https://www.trc-canada.com/product-detail/?CatNum=C781420
Toronto Research Chemicals	L468897	https://www.trc-canada.com/product-detail/?CatNum=L468897
eMolecules	300611343	https://orderbb.emolecules.com/search/#?query=300611343
eMolecules	36500936	https://orderbb.emolecules.com/search/#?query=36500936
eMolecules	49837452	https://orderbb.emolecules.com/search/#?query=49837452
eNovation Chemicals	D372294	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372294&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D509300	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D509300&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3313113908	https://mcule.com/MCULE-3313113908/
mcule	MCULE-6396594685	https://mcule.com/MCULE-6396594685/

PubMed

Title	Date	PubMed
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.	2009 Jan 22	19102698
Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis.	2009 Mar	19249987
In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB(1) receptor antagonist for the management of obesity.	2010 Apr 2	20211605

Patents

Sample Use Guides

In Vivo Use Guide

Three double-blind, placebo-controlled, three-parallel-group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP-945,598 (OTENABANT) for weight loss and weight-loss maintenance. In total, 1,253 and 2,536 participants in the two 2-year multinational and North American studies were randomized to 10-mg CP-945,598 (n = 360; 718); 20-mg CP-945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10-mg CP-945,598 (n = 318); 20-mg CP-945,598 (n = 320); and placebo (n = 337) in the 1-year multinational diabetes trial.

Route of Administration: Oral

In Vitro Use Guide

CP-945,598 (TENABANT) exhibits sub-nanomolar potency at human CB(1) receptors in both binding (K(i)=0.7 nM) and functional assays (K(i)=0.2 nM). The compound has low affinity (K(i)=7600 nM) for human CB(2) receptors.

Name

Type

Language

OTENABANT

Official Name

English

CP-945,598

Code

English

OTENABANT [USAN]

Common Name

English

4-PIPERIDINECARBOXAMIDE, 1-(8-(2-CHLOROPHENYL)-9-(4-CHLOROPHENYL)-9H-PURIN-6-YL)-4- (ETHYLAMINO)-

Systematic Name

English

CP-945598

Code

English

otenabant [INN]

Common Name

English

Otenabant [WHO-DD]

Common Name

English

1-(8-(2-CHLOROPHENYL)-9-(4-CHLOROPHENYL)-9H-PURIN-6-YL)-4-(ETHYLAMINO)PIPERIDINE-4- CARBOXAMIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29728