DIRLOTAPIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C40H33F3N4O3
Molecular Weight	674.7102
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CC1=CC=CC=C1)C(=O)[C@@H](NC(=O)C2=CC3=C(C=CC(NC(=O)C4=C(C=CC=C4)C5=CC=C(C=C5)C(F)(F)F)=C3)N2C)C6=CC=CC=C6

InChI

InChIKey=TUOSYWCFRFNJBS-BHVANESWSA-N

InChI=1S/C40H33F3N4O3/c1-46(25-26-11-5-3-6-12-26)39(50)36(28-13-7-4-8-14-28)45-38(49)35-24-29-23-31(21-22-34(29)47(35)2)44-37(48)33-16-10-9-15-32(33)27-17-19-30(20-18-27)40(41,42)43/h3-24,36H,25H2,1-2H3,(H,44,48)(H,45,49)/t36-/m0/s1

HIDE SMILES / InChI

Description

Dirlotapide is indicated for the management of obesity in dogs. Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor. It mainly acts locally in the gut to reduce appetite, increase fecal fat and produce weight loss in dogs. The adverse reactions associated with treatment with Dirlotapide include vomiting, loose stools/diarrhea, lethargy, and anorexia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 2D6 52	Inhibitor 7197
Microsomal triglyceride transfer protein 2	Inhibitor 7197	Obesity	1.5 nM [IC50]
Cytochrome P450 2C9 46	Inhibitor 7197
Cytochrome P450 3A 21	Inhibitor 7197
Cytochrome P450 2C19 46	Inhibitor 7197
Cytochrome P450 1A2 63	Inhibitor 7197

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 215	Primary	Microsomal triglyceride transfer protein	Approved 7777	SLENTROL

PubMed

Title	Date	PubMed
In vitro and in vivo profile of 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), a novel potent MTP inhibitor for obesity.	2007 Apr 1	17276061
Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America.	2007 Aug	17567518
An evaluation of dirlotapide to reduce body weight of client-owned dogs in two placebo-controlled clinical studies in Europe.	2007 Aug	17567517
Influence of dirlotapide, a microsomal triglyceride transfer protein inhibitor, on the digestibility of a dry expanded diet in adult dogs.	2007 Aug	17567516
Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers.	2007 Aug	17567515
The safety of dirlotapide in dogs.	2007 Aug	17567514
Biologic activity of dirlotapide, a novel microsomal triglyceride transfer protein inhibitor, for weight loss in obese dogs.	2007 Aug	17567513
Pharmacokinetics of dirlotapide in the dog.	2007 Aug	17567512
Absorption, distribution, metabolism, and excretion of dirlotapide in the dog.	2007 Aug	17567511
Dirlotapide: a review of its properties and role in the management of obesity in dogs.	2007 Aug	17567510
Canine obesity: an overview.	2007 Aug	17567509
Dirlotapide, a U.S. Food and Drug Administration-approved first-in-class obesity drug for dogs-will humans be next?	2007 May	19885086
Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo.	2008 Aug 5	18681965
The use of 18O-exchange and base-catalyzed N-dealkylation with liquid chromatography/tandem mass spectrometry to identify carbinolamide metabolites.	2010 Jul 30	20552706
Low-energy nanoemulsification to design veterinary controlled drug delivery devices.	2010 Oct 21	21042549

Patents

Sample Use Guides

In Vivo Use Guide

The initial dosage of SLENTROL is 0.01 mL/kg (0.0045 mL/lb) body weight, administered once daily, for the first 14 days. After the first 14 days of treatment, the dose volume of SLENTROL should be doubled to 0.02 mL/kg (0.009 mL/lb) of body weight, administered once daily for the next 14 days (days 15 to 28 of treatment). Dogs should be weighed monthly and the dose volume adjusted every month, as necessary, to maintain a target percent weight loss of ≥0.7% per week.

Route of Administration: Oral

In Vitro Use Guide

In a murine model investigating intestinal triglyceride transfer protein (MTP) inhibition, dirlotapide demonstrated potent inhibition of intestinal fat absorption with an ED25 of 0.16 mg/kg. In contrast, it was a poor inhibitor of hepatic MTP as demonstrated in a murine model of triglyceride lowering, where it had an ED25 of 6 mg/kg.

Name

Type

Language

DIRLOTAPIDE

Official Name

English

CP-742,033

Code

English

1H-INDOLE-2-CARBOXAMIDE, 1-METHYL-N-((1S)-2-(METHYL(PHENYLMETHYL)AMINO)-2-OXO-1-PHENYLETHYL)-5-(((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)CARBONYL)AMINO)-

Common Name

English

CP-742033

Code

English

DIRLOTAPIDE [GREEN BOOK]

Common Name

English

SLENTROL

Brand Name

English

DIRLOTAPIDE [INN]

Common Name

English

N-((1S)-2-(BENZYLMETHYLAMINO)-2-OXO-1-PHENYLETHYL)-1-METHYL-5-(((4'-(TRIFLUOROMETHYL)BIPHENYL-2-YL)CARBONYL)AMINO)-1H-INDOLE-2-CARBOXAMIDE

Common Name

English

DIRLOTAPIDE [USAN]

Common Name

English

DIRLOTAPIDE [EMA EPAR VETERINARY]

Common Name

English

DIRLOTAPIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29728