Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists

被引：104

作者：

Zarrinmayeh, H ^{[1
]}

Zimmerman, DM ^{[1
]}

Cantrell, BE ^{[1
]}

Schober, DA ^{[1
]}

Bruns, RF ^{[1
]}

Gackenheimer, SL ^{[1
]}

Ornstein, PL ^{[1
]}

Hipskind, PA ^{[1
]}

Britton, TC ^{[1
]}

Gehlert, DR ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(99)00082-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of benzimidazoles (4) was synthesized and evaluated in vitro as potent and selective NPY Y1 receptor antagonists. Substitution of the piperidine nitrogen of 4 with appropriate R groups resulted in compounds with more than 80-fold higher affinity at the Y1 receptor compared to the parent compound 5 (R = H). The most potent benzimidazole in this series was 21 (K-i = 0.052 nM). (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：647 / 652

页数：6

共 50 条

[1] Structure-activity relationships of a series of 1-substituted-4-methylbenzimidazole neuropeptide Y-1 receptor antagonists
Zimmerman, DM
Cantrell, BE
Smith, ECR
Nixon, JA
Bruns, RF
Gitter, B
Hipskind, PA
Ornstein, PL
Zarrinmayeh, H
Britton, TC
Schober, DA
Gehlert, DR
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (05) : 473 - 476
[2] Optimization of a series of 2,4-diaminopyridines as neuropeptide Y Y1 receptor antagonists with reduced hERG activity
Kameda, Minoru
Kobayashi, Kensuke
Ito, Hirokatsu
Miyazoe, Hiroshi
Tsujino, Toshiaki
Nakama, Chisato
Kawamoto, Hiroshi
Ando, Makoto
Ito, Sayaka
Suzuki, Tomoki
Kanno, Tetsuya
Tanaka, Takeshi
Tahara, Yoshio
Tani, Takeshi
Tanaka, Sachiko
Tokita, Shigeru
Sato, Nagaaki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (15) : 4325 - 4329
[3] Neuropeptide Y and neuropeptide Y1 receptor expression in the rat retina
D'Angelo, I
Brecha, NC
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 1999, 40 (04) : S439 - S439
[4] Neuropeptide Y as a partial agonist of the Y1 receptor
Sah, R
Balasubramaniam, A
Parker, MS
Sallee, F
Parker, SL
EUROPEAN JOURNAL OF PHARMACOLOGY, 2005, 525 (1-3) : 60 - 68
[5] Design, synthesis and evaluation of a novel cyclohexanamine class of neuropeptide Y Y1 receptor antagonists
Cho, Kaimei
Ando, Makoto
Kobayashi, Kensuke
Miyazoe, Hiroshi
Tsujino, Toshiaki
Ito, Sayaka
Suzuki, Tomoki
Tanaka, Takeshi
Tokita, Shigeru
Sato, Nagaaki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (16) : 4781 - 4785
[6] Dental pulp fibroblasts express neuropeptide Y Y1 receptor but not neuropeptide Y
Killough, S. A.
Lundy, F. T.
Irwin, C. R.
INTERNATIONAL ENDODONTIC JOURNAL, 2010, 43 (10) : 835 - 842
[7] INVESTIGATIONS OF THE STRUCTURE-ACTIVITY RELATIONSHIP OF NEUROPEPTIDE-Y
CADIEUX, A
TBENCHEKROUN, M
FOURNIER, A
STPIERRE, S
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 611 : 369 - 371
[8] NEUROPEPTIDE-Y RECEPTOR SUBTYPES, Y1 AND Y2
WAHLESTEDT, C
GRUNDEMAR, L
HAKANSON, R
HEILIG, M
SHEN, GH
ZUKOWSKAGROJEC, Z
REIS, DJ
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 611 : 7 - 26
[9] Synthesis and evaluation of substituted 4-alkoxy-2-aminopyridines as novel neuropeptide Y1 receptor antagonists
Sato, N
Shibata, T
Jitsuoka, M
Ohno, T
Takahashi, T
Hirohashi, T
Kanno, T
Iwaasa, H
Kanatani, A
Fukami, T
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (07) : 1761 - 1764
[10] STRUCTURE-ACTIVITY RELATIONSHIP OF NOVEL PENTAPEPTIDE NEUROPEPTIDE-Y RECEPTOR ANTAGONISTS IS CONSISTENT WITH A NONCONTINUOUS EPITOPE FOR LIGAND-RECEPTOR BINDING
DANIELS, AJ
MATTHEWS, JE
VIVEROS, OH
LEBAN, JJ
CORY, M
HEYER, D
MOLECULAR PHARMACOLOGY, 1995, 48 (03) : 425 - 432

← 1 2 3 4 5 →