Structure-activity study of L-cysteine-based N-type calcium channel blockers: Optimization of N- and C-terminal substituents

被引：18
|
作者：
Seko, T [1 ]
Kato, M [1 ]
Kohno, H [1 ]
Ono, S [1 ]
Hashimura, K [1 ]
Takimizu, H [1 ]
Nakai, K [1 ]
Maegawa, H [1 ]
Katsube, N [1 ]
Toda, M [1 ]
机构：
[1] Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka 6188585, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 06期
关键词：
D O I：
10.1016/S0960-894X(02)00032-X
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Synthesis and structure-activity relationship (SAR) studies of L-cysteine-based N-type calcium channel blockers are described. In the course of exploring SAR of the N- and C-terminal substituents, the L-cysteine derivative 4b was found to be a potent N-type calcium channel blocker with an IC50 value of 0.14 muM on IMR-32 assay. Compound 4b showed 12-fold selectivity for N-type over L-type calcium channels on AtT-20 assay. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：915 / 918
页数：4
相关论文
共 50 条
  • [11] Structure-Activity Analysis of N-Type Calcium Channel Inhibitor SO-3
    Dong, Minxing
    Wang, Fei
    Yan, Zhenzhen
    Yu, Shuo
    Wei, Juanjuan
    Wu, Qiaoling
    Liu, Zhuguo
    Tang, Yifei
    Ding, Jiuping
    Dai, Qiuyun
    BIOCHEMISTRY, 2018, 57 (44) : 6349 - 6355
  • [12] Synthesis and structure-activity relationship of substituted 1,2,3,4-tetrahydroisoquinolines as N-type calcium channel blockers
    Yuen, PW
    Schelkun, RM
    Szoke, B
    Tarczy-Hornoch, K
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (18) : 2415 - 2418
  • [13] Synthesis and structure activity relationship of substituted quinoline and isoquinoline derivatives as N-type calcium channel blockers
    Yuen, PW
    Schelkun, RM
    Szoke, B
    TarczyHornoch, K
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1997, 214 : 5 - MEDI
  • [14] Multifunctional L/N- and L/T-type calcium channel blockers for kidney protection
    Abe, Masanori
    Soma, Masayoshi
    HYPERTENSION RESEARCH, 2015, 38 (12) : 804 - 806
  • [15] Multifunctional L/N- and L/T-type calcium channel blockers for kidney protection
    Masanori Abe
    Masayoshi Soma
    Hypertension Research, 2015, 38 : 804 - 806
  • [16] Scaffold-based design and synthesis of potent N-type calcium channel blockers
    Zamponi, Gerald W.
    Feng, Zhong-Ping
    Zhang, Lingyun
    Pajouhesh, Hossein
    Ding, Yanbing
    Belardetti, Francesco
    Pajouhesh, Hassan
    Dolphin, David
    Mitscher, Lester A.
    Snutch, Terrance P.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (22) : 6467 - 6472
  • [17] Discovery, structure-activity relationship study, and oral analgesic efficacy of cyproheptadine derivatives possessing N-type calcium channel inhibitory activity
    Yamamoto, Takashi
    Niwa, Seiji
    Iwayama, Satoshi
    Koganei, Hajime
    Fujita, Shin-ichi
    Takeda, Tomoko
    Kito, Morikazu
    Ono, Yukitsugu
    Saitou, Yuki
    Takahara, Akira
    Iwata, Seinosuke
    Yamamoto, Hiroshi
    Shoji, Masataka
    BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (15) : 5333 - 5339
  • [18] The Regulation of N-Type (cav2.2) Voltage-Gated Calcium Channels by Cavβ Subunit N- and C-terminal Variable Domains
    Song, Lele
    Roberts, Laura
    Fitzgerald, Elizabeth
    BIOPHYSICAL JOURNAL, 2010, 98 (03) : 694A - 694A
  • [19] Structure-activity relationship at the proximal phenyl group in a series of nonpeptidyl N-type calcium channel antagonists.
    Ryder, TR
    Hu, LY
    Rafferty, MF
    Lotarski, SM
    Rock, DM
    Stoehr, SJ
    Taylor, CP
    Weber, ML
    Millerman, E
    Miljanich, GP
    Szoke, BG
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2000, 219 : U48 - U48
  • [20] L/T-type and L/N-type calcium-channel blockers attenuate cardiac sympathetic nerve activity in patients with hypertension
    Ogura, Chika
    Ono, Koh
    Miyamoto, Shoichi
    Ikai, Akiko
    Mitani, Satoko
    Sugimoto, Naozo
    Tanaka, Shiro
    Fujita, Masatoshi
    BLOOD PRESSURE, 2012, 21 (06) : 367 - 371
12345