TARANABANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H25ClF3N3O2
Molecular Weight	515.955
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](NC(=O)C(C)(C)OC1=CC=C(C=N1)C(F)(F)F)[C@@H](CC2=CC=C(Cl)C=C2)C3=CC=CC(=C3)C#N

InChI

InChIKey=QLYKJCMUNUWAGO-GAJHUEQPSA-N

InChI=1S/C27H25ClF3N3O2/c1-17(34-25(35)26(2,3)36-24-12-9-21(16-33-24)27(29,30)31)23(14-18-7-10-22(28)11-8-18)20-6-4-5-19(13-20)15-32/h4-13,16-17,23H,14H2,1-3H3,(H,34,35)/t17-,23+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C27H25ClF3N3O2
Molecular Weight	515.955
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugdevelopment-technology.com/projects/taranabant/
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19597516

Taranabant is a highly selective cannabinoid-1 (CB1) receptor inverse agonist developed by Merck & Co for the treatment of obesity. The Phase III taranabant study involved about 2,400 patients and was to be conducted for two years. In March 2008, after completion of 52 weeks of the study, Merck reported positive results of the drug in conjunction with diet and exercise in obese patients. The patients experienced double the amount of weight loss by taking 2mg of taranabant when compared to the patients treated with placebo. However, in October 2008, the company discontinued the Phase III programme and clinical development of taranabant because of its side effects. The drug showed gastrointestinal and psychiatric side effects such as increased anxiety, depression and irritability. Merck had previously planned to file for regulatory approval with the US Food and Drug Administration in 2008, but subsequently withdrew it.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cannabinoid CB1 receptor 85 Target ID: CHEMBL218 Sources: http://www.drugdevelopment-technology.com/projects/taranabant/	Inverse Agonist 80		0.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203 Sources: https://clinicaltrials.gov/ct2/show/NCT00420589	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
49.99 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
58.24 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	7.5 mg 1 times / day steady-state, oral dose: 7.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
85.62 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
147.55 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
265.2 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
298.3 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	7.5 mg 1 times / day steady-state, oral dose: 7.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
416.4 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
806.3 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
90.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
93.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	7.5 mg 1 times / day steady-state, oral dose: 7.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
97.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
103.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18508950	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TARANABANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

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
CYP1A2 1524	CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20673729/	weak [IC50 >20.0 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20673729/	yes [IC50 0.59 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20673729/	yes [IC50 0.93 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20673729/	yes [IC50 >20.0 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://doi.org/10.1002/j.1930-739X.2007.tb00011.x	major	yes (co-administration study) Comment: Coadministration of Ketoconazole or Diltiazem increased Taranabant AUCinf by 15.0-fold or 4.6-fold Sources: https://doi.org/10.1002/j.1930-739X.2007.tb00011.x
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20608842/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20608842/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20608842/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20608842/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20608842/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20608842/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.20311

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00FCHR	https://www.1pchem.com/search?query=1P00FCHR
AK Scientific	4085AH	https://aksci.com/item_detail.php?cat=4085AH
Alfa Chemistry	ACM701977095	http://www.alfa-chemistry.com/search.aspx?q=ACM701977095
Axon MedChem	1550	https://www.axonmedchem.com/product/1550
BOC Sciences	701977-09-5	http://www.bocsci.com/description.asp?cas=701977-09-5
Chem Scene	CS-0289	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0289
MedChem Express	HY-10013	https://www.medchemexpress.com/search.html?q=HY-10013&ft=&fa=&fp=
MolPort	MolPort-020-014-681	https://www.molport.com/shop/molecule-link/MolPort-020-014-681
Molnova	M15693	https://www.molnova.com/en/serch-list.html?keywords=M15693
Molnova	M15694	https://www.molnova.com/en/serch-list.html?keywords=M15694
MuseChem	I004634	https://www.musechem.com/product/I004634.html
ShangHai Biochempartner	BCP21059	http://www.biochempartner.com/search_BCP21059
Toronto Research Chemicals	T007655	https://www.trc-canada.com/product-detail/?CatNum=T007655
eMolecules	275085259	https://orderbb.emolecules.com/search/#?query=275085259
eMolecules	300579887	https://orderbb.emolecules.com/search/#?query=300579887
eMolecules	36745697	https://orderbb.emolecules.com/search/#?query=36745697
mcule	MCULE-1712420834	https://mcule.com/MCULE-1712420834/
mcule	MCULE-3539984542	https://mcule.com/MCULE-3539984542/

PubMed

Title	Date	PubMed
		252160245
Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364), in rodents.	2007 Jun	17327489
The endocannabinoid system as a target for obesity treatment.	2008	19046740

Patents

Sample Use Guides

In Vivo Use Guide

0.5 mg capsule, 1 mg capsule, 2 mg capsule once daily. Treatment for 52 weeks.

Route of Administration: Oral

In Vitro Use Guide

In vitro, taranabant (10(-10) -10(-7) mol/L) increased contractile responses in mouse ileum and blocked the effect of the CB agonist WIN 55,212-2.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:47:02 GMT 2023` Edited by `admin` on `Sat Dec 16 16:47:02 GMT 2023`
Record UNII	X9U622S114
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TARANABANT

Official Name

English

MK-0364

Code

English

TARANABANT [USAN]

Common Name

English

Taranabant [WHO-DD]

Common Name

English

MK0364

Code

English

N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide

Systematic Name

English

PROPANAMIDE, N-((1S,2S)-3-(4-CHLOROPHENYL)-2-(3-CYANOPHENYL)-1-METHYLPROPYL)-2-METHYL-2-((5-(TRIFLUOROMETHYL)-2-PYRIDINYL)OXY)-

Systematic Name

English

taranabant [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29728