Discovery of novel tricyclic compounds as squalene synthase inhibitors

Bioorganic and Medicinal Chemistry

Volumn 20, Issue 9, 2012, Pages 3072-3093

  Ichikawa, Masanori ^a   Ohtsuka, Masami ^a   Ohki, Hitoshi ^a   Haginoya, Noriyasu ^a   Itoh, Masao ^a   Sugita, Kazuyuki ^b   Usui, Hiroyuki ^a   Suzuki, Makoto ^a   Terayama, Koji ^a   Kanda, Akira ^a  

^a DAIICHI SANKYO CO   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

Author keywords

Hypercholesterolemia; Lipid lowering effect; Pyrrolobenzoxazepine; Squalene synthase inhibitor

Indexed keywords

1 [4 CHLORO 2 (1 NAPHTHOYL)PHENYL] 1H PYRROL 2 CARBALDEHYDE; 1 [4 CHLORO 2 (2,3 DIMETHOXYBENZOYL)PHENYL] 1H PYRROLE 2 CARBALDEHYDE; 1,4 BENZDIOXANE 8 YL; 2 [1 [2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETYL] 4 PIPERIDINYL]ACETIC ACID; 2 [1,8 DICHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; 2 [8 CHLORO 6 (1 NAPHTHYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; 2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 1 (4 MORPHOLINYLMETHYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; 2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 1 [(DIMETHYLAMINO)METHYL] 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; 2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; [5 CHLORO 2 (1H PYRROL 1 YL)PHENYL](1 NAPHTHYL)METHANOL; [5 CHLORO 2 (1H PYRROL 1 YL)PHENYL](2,3 DIMETHOXYPHENYL)METHANONE; ANTILIPEMIC AGENT; ASN 215; BENZHYDROL DERIVATIVE; BENZOXAZEPINE DERIVATIVE; CHOLESTEROL SYNTHESIS INHIBITOR; CP 320473; ETHYL 2 [1 [2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETYL] 4 PIPERIDINYL]ACETATE; ETHYL 2 [1 [2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETYL] 4 PIPERIDINYL]ACETIC ACID; HYPOCHOLESTEROLEMIC AGENT; METHYL 2 [1,8 DICHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; METHYL 2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 1 (4 MORPHOLINYLMETHYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; METHYL 2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 1 [(DIMETHYLAMINO)METHYL] 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; METHYL 2 [8 CHLORO 6 (2,3 DIMETHOXYPHENYL) 4H,6H PYRROLO[1,2 A][4,1]BENZOXAZEPIN 4 YL]ACETIC ACID; METHYL 3 [1 [4 CHLORO 2 (1 NAPHTHOYL)PHENYL] 1H PYRROL 2 YL] 2 PROPENOIC ACID; METHYL 3 [1 [4 CHLORO 2 (2,3 DIMETHOXYBENZOYL)PHENYL] 1H PYRROL 2 YL] 2 PROPENOIC ACID; METHYL 3 [1 [4 CHLORO 2 [(2,3 DIMETHOXYPHENYL)(HYDROXY)METHYL]PHENYL] 1H PYRROL 2 YL] 2 PROPENOIC ACID; PYRROLOBENZOXAZEPINE DERIVATIVE; SQUALENE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTILIPEMIC ACTIVITY; ARTICLE; CALLITRICHINAE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; NONHUMAN; RAT; REPEATED DRUG DOSE; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; ANTICHOLESTEREMIC AGENTS; BENZHYDRYL COMPOUNDS; BINDING SITES; CALLITHRIX; CATALYTIC DOMAIN; CELLS, CULTURED; COMPUTER SIMULATION; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME ACTIVATION; ENZYME INHIBITORS; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; HEPATOCYTES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84862798487     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.02.054     Document Type: Article

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