Structural optimization of ghrelin receptor inverse agonists to improve lipophilicity and avoid mechanism-based CYP3A4 inactivation

Chemical and Pharmaceutical Bulletin

Volumn 63, Issue 10, 2015, Pages 825-832

  Takahashi, Bitoku ^a   Funami, Hideaki ^a   Shibata, Makoto ^a   Maruoka, Hiroshi ^a   Koyama, Makoto ^a   Kanki, Satomi ^a   Muto, Tsuyoshi ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

Ghrelinr; Inverse agonist; Ligand lipophilicity efficiency; Mechanism based inactivation; Obesity

Indexed keywords

1,3 BENZODIOXOLE DERIVATIVE; 2 [[(2,2 DIFLUOROBENZO[ D ][1,3]DIOXOL 5 YL)METHYL]AMINO] N [3 (DIFLUOROMETHYL) 4 METHYLBENZYL] 5 [3 METHYL 3 (METHYLSULFONAMIDO)BUT 1 YL]NICOTINAMIDE; 6 AMINONICOTINAMIDE; CYTOCHROME P450 3A4; GHRELIN RECEPTOR; HORMONE RECEPTOR STIMULATING AGENT; LEAD; LIGAND; N [3 (DIF LUOROMETHYL) 4 METHYLBENZYL] 2 [[(2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHYL]AMINO] 5 (3 HYDROXY 3 METHYLBUT 1 YN)NICOTINAMIDE; N [3 (DIFLUOROMETHYL) 4 METHYLBENZYL] 2 [[(4 METHOXYPYR 2 YL)METHYL]AMINO] 5 [3 METHYL 3 (METHYLSULFONAMIDO)BUT 1 YN1 YL]NICOTINAMIDE; N [3 (DIFLUOROMETHYL) 4 METHYLBENZYL] 5 (3 HYDROXY 3 METHYLBUT 1 YN 1 YL) 2 [(IMIDAZO[1,2 B]PYRIDAZIN 2 YLMETHYL)AMINO]NICOTINAMIDE; N [[6 (DIFLUOROMETHYL) 5 METHYLPYRIDIN 2 YL]METHYL] 2 [[(2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL)METHYL]AMINO] 5 [3 METHYL 3 (METHYLSULFONAMIDO)BUT 1 YN YL]NICOTINAMIDE HYDROCHLORIDE; N [[6 (DIFLUOROMETHYL) 5 METHYLPYRIDIN 2 YL]METHYL] 2 [[(4 METHOXYPYRIDIN 2 YL)METHYL]AMINO] 5 [3 METHYL 3 (METHYLSULFONAMIDO)BUT 1 YN 1 YL]NICOTINAMIDE; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; ANTIOBESITY AGENT; CYTOCHROME P450 3A;

ARTICLE; DRUG SYNTHESIS; ENZYME ACTIVATION; HUMAN; HUMAN CELL; IC50; LIPOPHILICITY; NONHUMAN; RAT; STRUCTURE ANALYSIS; AGONISTS; ANALOGS AND DERIVATIVES; CHEMISTRY; DRUG DEVELOPMENT; INVERSE AGONISM; LIVER MICROSOME; METABOLISM; OBESITY;

6-AMINONICOTINAMIDE; ANTI-OBESITY AGENTS; CYTOCHROME P-450 CYP3A; DRUG DISCOVERY; DRUG INVERSE AGONISM; HUMANS; MICROSOMES, LIVER; OBESITY; RECEPTORS, GHRELIN;

EID: 84947779762     PISSN: 00092363     EISSN: 13475223     Source Type: Journal    
DOI: 10.1248/cpb.c15-00285     Document Type: Article

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