Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6- methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3- d ]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor

Journal of Medicinal Chemistry

Volumn 54, Issue 14, 2011, Pages 4998-5012

  Miwa, Kazuhiro ^a   Hitaka, Takenori ^a   Imada, Takashi ^a   Sasaki, Satoshi ^a   Yoshimatsu, Mie ^a   Kusaka, Masami ^a   Tanaka, Akira ^a   Nakata, Daisuke ^a   Furuya, Shuichi ^a   Endo, Satoshi ^a   Hamamura, Kazumasa ^a   Kitazaki, Tomoyuki ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 [1 (2,6 DIFLUOROBENZYL) 3 (2 ETHOXYETHYL) 5 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 2,4 DIOXO 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 3 (2 HYDROXY 2 METHYLPROPYL) 5 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 2,4 DIOXO 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 3 (2 HYDROXYETHYL) 5 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 2,4 DIOXO 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 3 (2 METHOXYETHYL) 5 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 2,4 DIOXO 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [(DIMETHYLAMINO)METHYL] 3 (6 METHOXYPYRIDAZIN 3 YL) 2,4 DIOXO 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [(METHYLAMINO)METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 2,4 DIOXO 3 (PYRIDIN 2 YL) 1,2,3,4 TETRAHYDROTHIENO[ 2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[(METHYL)[2 (1H 1,2,3-TRIAZOL 1 YL)ETHYL]AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[[[6 (HYDROXYMETHYL)PYRIDIN 2 YL]METHYL](METHYL)AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[METHYL(2 PYRIDIN 2 YL ETHYL)AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[METHYL(PYRIDIN 2 YLMETHYL)AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[METHYL(PYRIDIN 3 YLMETHYL)AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 1 [4 [1 (2,6 DIFLUOROBENZYL) 5 [[METHYL[2 (2 OXOPYRROLIDIN 1 YL)ETHYL]AMINO]METHYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 6 YL]PHENYL] 3 METHOXYUREA; 2 [(2,6 DIFLUOROBENZYL)(ETHOXYCARBONYL)AMINO] 5 [4 [[(METHOXYCARBAMOYL)AMINO]PHENYL] 4 [(2 METHOXYETHYL)(METHYL)AMINO]METHYL]THIOPHENE 3 CARBOXYLIC ACID; BOVINE SERUM ALBUMIN; CYTOCHROME P450; ELAGOLIX; ETHYL 2 [(2,6 DIFLUOROBENZYL)(ETHOXYCARBONYL)AMINO] 4 METHYL 5 (4 NITROPHENYL)THIOPHENE 3 CARBOXYLATE; ETHYL 2 [(2,6 DIFLUOROBENZYL)(ETHOXYCARBONYL)AMINO] 5 [4 [(METHOXYCARBAMOYL)AMINO]PHENYL] 4 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL]THIOPHENE 3 CARBOXYLATE; ETHYL 2 [(2,6 DIFLUOROBENZYL)(ETHOXYCARBONYL)AMINO]4 [[(2 METHOXYETHYL)(METHYL)AMINO]METHYL] 5 (4 NITROPHENYL)THIOPHENE 3 CARBOXYLATE; ETHYL 2 [(ETHOXYCARBONYL)AMINO] 4 METHYL 5 (4 NITROPHENYL)THIOPHENE 3 CARBOXYLATE; ETHYL 4 (BROMOMETHYL) 2 [(2,6 DIFLUOROBENZYL)(ETHOXYCARBONYL)AMINO] 5 (4 NITROPHENYL)THIOPHENE 3 CARBOXYLATE; ETHYL 5 (4 AMINOPHENYL) 2 [(2,6 DIFLUOROBENZYL)(ETHOXYCARBONYL)AMINO] 4 [[(2 METHOXYETHYL)(METHYL)AMINO] METHYL]THIOPHENE 3 CARBOXYLATE; GONADORELIN ANTAGONIST; GONADORELIN RECEPTOR; LUTEINIZING HORMONE; N [2 [[[1 (2,6 DIFLUOROBENZYL) 6 [4 [[(METHOXYAMINO) CARBONYL]AMINO]PHENYL] 2,4 DIOXO 3 PHENYL 1,2,3,4 TETRAHYDROTHIENO[2,3 D]PYRIMIDIN 5 YL]METHYL](METHYL)AMINO]ETHYL] N METHYLMETHANESULFONAMIDE; SUFUGOLIX; TAK 385; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG ABSORPTION; DRUG ACTIVITY; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; HAPLORHINI; HUMAN; HUMAN CELL; IC 50; LUTEINIZING HORMONE BLOOD LEVEL; MATHEMATICAL COMPUTING; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ANIMALS; CATTLE; CHO CELLS; CRICETINAE; CRICETULUS; CYTOCHROME P-450 CYP3A; HUMANS; MACACA FASCICULARIS; MALE; MODELS, MOLECULAR; PHENYLUREA COMPOUNDS; PYRIMIDINONES; RADIOLIGAND ASSAY; RATS; RECEPTORS, LHRH; SPECIES SPECIFICITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79960619350     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200216q     Document Type: Article

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