MK-0557

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H19FN4O3
Molecular Weight	406.4097
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=CC=C1N2C=CC(NC(=O)[C@H]3CC[C@@]4(CC3)OC(=O)C5=C4C=NC=C5)=N2

InChI

InChIKey=RMYZIRFUCOMQRH-CAJLXGCNSA-N

InChI=1S/C22H19FN4O3/c23-17-3-1-2-4-18(17)27-12-8-19(26-27)25-20(28)14-5-9-22(10-6-14)16-13-24-11-7-15(16)21(29)30-22/h1-4,7-8,11-14H,5-6,9-10H2,(H,25,26,28)/t14-,22-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17011500 | https://www.ncbi.nlm.nih.gov/pubmed/17426325 | https://www.ncbi.nlm.nih.gov/pubmed/17712121 | https://clinicaltrials.gov/ct2/show/NCT00482430 | http://adisinsight.springer.com/drugs/800029448

MK-0557, trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro [6 azaisobenzofuran-1(3H),10-cyclohexane]-40-carboxamide, is an orally available Neuropeptide Y (NPY5) receptor antagonist. MK-0557 was studied in the clinical trials for the treatment of obesity, however, MK-0557 did not significantly increase the weight loss efficacy. MK-0557 safety and effectiveness were studied in a trial for the treatment of cognitive impairment in patients with schizophrenia. It seems MK-0557 development was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neuropeptide Y receptor type 5 5 Target ID: CHEMBL4561 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17011500	Antagonist 2778		1.3 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17712121 https://www.ncbi.nlm.nih.gov/pubmed/17426325 https://www.ncbi.nlm.nih.gov/pubmed/17011500	Primary		Phase III 656	Unknown Approved Use Unknown
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT00482430	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1.13 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17011500	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-055 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.07 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17011500	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-0557 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
62.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17011500	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-055 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17011500	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-0557 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
30 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17011500	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-055 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17011500	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MK-0557 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1 mg 1 times / day multiple, oral Studied dose Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17426325 Page: p.901	unhealthy n = 182 Health Status: unhealthy Condition: Obesity Sex: M+F Population Size: 182 Sources: https://pubmed.ncbi.nlm.nih.gov/17426325 Page: p.901	Sources: https://pubmed.ncbi.nlm.nih.gov/17426325 Page: p.901

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01EG84	https://www.1pchem.com/search?query=1P01EG84
AChemBlock	O32835	http://www.achemblock.com/catalogsearch/result/?q=O32835
BLD Pharm	BD00805104	http://www.bldpharm.com/search/Search.html?keyword=BD00805104
Chem Scene	CS-6367	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6367
Excenen	EX-A1270	http://www.excenen.com/searchresultlist.php?id=EX-A1270
MedChem Express	HY-15411	https://www.medchemexpress.com/search.html?q=HY-15411&ft=&fa=&fp=
MolPort	MolPort-044-727-695	https://www.molport.com/shop/molecule-link/MolPort-044-727-695
MolPort	MolPort-046-417-053	https://www.molport.com/shop/molecule-link/MolPort-046-417-053
MuseChem	I008012	https://www.musechem.com/product/I008012.html
eMolecules	189882759	https://orderbb.emolecules.com/search/#?query=189882759
eMolecules	207839940	https://orderbb.emolecules.com/search/#?query=207839940
eMolecules	275085197	https://orderbb.emolecules.com/search/#?query=275085197
eMolecules	303864446	https://orderbb.emolecules.com/search/#?query=303864446
eMolecules	313087025	https://orderbb.emolecules.com/search/#?query=313087025
mcule	MCULE-7073849062	https://mcule.com/MCULE-7073849062/

PubMed

Title	Date	PubMed
Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults.	2006 Oct	17011500
Effect of NPY5R antagonist MK-0557 on weight regain after very-low-calorie diet-induced weight loss.	2007 Apr	17426325
NPY5R antagonism does not augment the weight loss efficacy of orlistat or sibutramine.	2007 Aug	17712121
Obesity and the central nervous system.	2007 Sep 1	17766646
Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist.	2009 Oct 1	19720539

Patents

Sample Use Guides

In Vivo Use Guide

The initial series of experiments reported herein, including a multiple-dose positron-emission tomography study and a 12 week proof-of concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The hypothesis was then tested in a 52 week, multicenter, randomized, double-blind, placebo-controlled trial involving 1661 overweight and obese patients. Although statistically significant at 52 weeks, the magnitude of induced weight loss was not clinically meaningful.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

MK-0557

Common Name

English

MK0557

Code

English

SPIRO(CYCLOHEXANE-1,3'(1'H)-FURO(3,4-C)PYRIDINE)-4-CARBOXAMIDE, N-(1-(2-FLUOROPHENYL)-1H-PYRAZOL-3-YL)-1'-OXO-, TRANS-

Common Name

English

Code System Code Type Description

PUBCHEM

11491176