Syntheses and structure-activity relationship studies of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists

被引：22

作者：

Jiang, JL

DeVita, RJ

Goulet, MT

Wyvratt, WJ

Lo, JL

Ren, N

Yudkovitz, JB

Cui, JS

Yang, YT

Cheng, K

Rohrer, SP

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Atherosclerosis & Endocrinol, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 07期

关键词：

D O I：

10.1016/j.bmcl.2003.12.101

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Syntheses and structure-activity relationships of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists are described. Some of substituents on the piperidine ring that were investigated included a fused phenyl group, a (6R)-trifluoromethyl group, (6S) and (6R)-methyl group. This study showed that GnRH binding potency was tolerated by a small group at the 6-position of the piperidine, and blocking the 6-position by a trifluoromethyl group reduced clearance rate and increased oral bioavailability. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1795 / 1798

页数：4

相关论文

共 8 条

[1] ALPHA-LITHIOAMINE SYNTHETIC EQUIVALENTS - SYNTHESES OF DIASTEREOISOMERS FROM THE BOC PIPERIDINES [J].

BEAK, P ;

LEE, WK .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (09) :2578-2580

[2] Identification and initial structure-activity relationships of a novel non-peptide quinolone GnRH receptor antagonist [J].

DeVita, RJ ;

Hollings, DD ;

Goulet, MT ;

Wyvratt, MJ ;

Fisher, MH ;

Lo, JL ;

Yang, YT ;

Cheng, K ;

Smith, RG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (17) :2615-2620

[3] Investigation of the 4-O-alkylamine substituent of non-peptide quinolone GnRH receptor antagonists [J].

DeVita, RJ ;

Goulet, MT ;

Wyvratt, MJ ;

Fisher, MH ;

Lo, JL ;

Yang, YT ;

Cheng, K ;

Smith, RG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (17) :2621-2624

[4] A potent, nonpeptidyl 1H-quinolone antagonist for the gonadotropin-releasing hormone receptor [J].

DeVita, RJ ;

Walsh, TF ;

Young, JR ;

Jiang, JL ;

Ujjainwalla, F ;

Toupence, RB ;

Parikh, M ;

Huang, SX ;

Fair, JA ;

Goulet, MT ;

Wyvratt, MJ ;

Lo, JL ;

Ren, N ;

Yudkovitz, JB ;

Yang, YT ;

Cheng, K ;

Cui, JS ;

Mount, G ;

Rohrer, SP ;

Schaeffer, JM ;

Rhodes, L ;

Drisko, JE ;

McGowan, E ;

MacIntyre, DE ;

Vincent, S ;

Carlin, JR ;

Cameron, J ;

Smith, RG .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (06) :917-922

[5] Asymmetric synthesis of chiral, nonracemic trifluoromethyl-substituted piperidines and decahydroquinolines [J].

Jiang, JL ;

DeVita, RJ ;

Doss, GA ;

Goulet, MT ;

Wyvratt, MJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (03) :593-594

[6] A NOVEL ASYMMETRIC ROUTE TO CHIRAL, NONRACEMIC CIS-2,6-DISUBSTITUTED PIPERIDINES - SYNTHESIS OF (+)-PINIDINONE AND (+)-MONOMORINE [J].

MUNCHHOF, MJ ;

MEYERS, AI .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (19) :5399-5400

[7] Potent antagonists of gonadotropin releasing hormone receptors derived from quinolone-6-carboxamides [J].

Walsh, TF ;

Toupence, RB ;

Young, JR ;

Huang, SX ;

Ujjainwalla, F ;

DeVita, RJ ;

Goulet, MT ;

Wyvratt, MJ ;

Fisher, MH ;

Lo, JL ;

Ren, N ;

Yudkovitz, JB ;

Yang, YT ;

Cheng, K ;

Smith, RG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (05) :443-447

[8] Quinolones as gonadotropin releasing hormone (GnRH) antagonists: Simultaneous optimization of the C(3)-aryl and C(6)-substituents [J].

Young, JR ;

Huang, SX ;

Chen, I ;

Walsh, TF ;

DeVita, RJ ;

Wyvratt, MJ ;

Goulet, MT ;

Ren, N ;

Lo, J ;

Yang, YT ;

Yudkovitz, JB ;

Cheng, K ;

Smith, RG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (15) :1723-1727