Inhibitor Report for: MK0626 General
Type Pyridine , Pyrrolidine , Triazol Chemical_Nomenclature (2S,3S)-3-amino-4-[(3S)-3-fluoropyrrolidin-1-yl]-N,N-dimethyl-4-oxo-2-[4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl]butanamide Canonical SMILES CN(C)C(=O)C(C1=CC=C(C=C1)C2=CN3C(=NC=N3)C=C2)C(C(=O)N4CCC(C4)F)N InChI InChI=1S/C22H25FN6O2/c1-27(2)21(30)19(20(24)22(31)28-10-9-17(23)12-28)15-5-3-14(4-6-15)16-7-8-18-25-13-26-29(18)11-16/h3-8,11,13,17,19-20H,9-10,12,24H2,1-2H3/t17-,19-,20-/m0/s1 InChIKey ZNHVIJAGMFQGMS-IHPCNDPISA-N Other name(s) DB08504 ; MK-0626 ; CHEMBL537869 ; CHEMBL237337 ; 6-(4-{(1S,2S)-2-AMINO-1-[(DIMETHYLAMINO)CARBONYL]-3-[(3S)-3-FLUOROPYRROLIDIN-1-YL]-3-OXOPROPYL}PHENYL)-1H-[1,2,4]TRIAZOLO[1,5-A]PYRIDIN-4-IUM ; 2fjp ; SCHEMBL14591260 ; BDBM50221972
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Target
Families | MK0626 ligand of proteins in family: DPP4N_Peptidase_S9 Stucture | 1 structure : 2FJP : Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor Protein | human-DPP4
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MK0626
Title: (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Edmondson SD , Mastracchio A , Mathvink RJ , He J , Harper B , Park YJ , Beconi M , Di Salvo J , Eiermann GJ and Weber AE <16 more author(s)>
Edmondson SD , Mastracchio A , Mathvink RJ , He J , Harper B , Park YJ , Beconi M , Di Salvo J , Eiermann GJ , He H , Leiting B , Leone JF , Levorse DA , Lyons K , Patel RA , Patel SB , Petrov A , Scapin G , Shang J , Roy RS , Smith A , Wu JK , Xu S , Zhu B , Thornberry NA , Weber AE (- 16)
Ref: Journal of Medicinal Chemistry, 49 :3614, 2006 : PubMed Abstract ESTHER: Edmondson_2006_J.Med.Chem_49_3614 PubMedSearch: Edmondson 2006 J.Med.Chem 49 3614 PubMedID: 16759103 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: MK0626 Abstract
A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]tr iazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.