Structure-activity relationships of novel, highly potent, selective, and orally active CCRI antagonists

被引：17
|
作者：
Xie, Yun Feng
Lake, Kirk
Ligsay, Kathleen
Komandla, Mallareddy
Sircar, Ila
Nagarajan, Gobi
Li, Jian
Xu, Kui
Parise, Jason
Schneider, Lisa
Huang, Ding
Liu, Juping
Dines, Kevin
Sakurai, Naoki
Barbosa, Miguel
Jack, Rick
机构：
[1] Tanabe Res Labs Inc, Dept Chem, San Diego, CA 92121 USA
[2] Tanabe Res Labs Inc, Dept Biol, San Diego, CA 92121 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 12期
关键词：
chemokine receptor 1; CCR1; antagonist; diaminocyclobutenedione;
D O I：
10.1016/j.bmcl.2007.03.104
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCRI antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3367 / 3372
页数：6
相关论文
共 50 条
  • [1] Synthesis and structure-activity relationships of potent and orally active sulfonamide ETB selective antagonists
    Kanda, Y
    Kawanishi, Y
    Oda, K
    Sakata, T
    Mihara, S
    Asakura, K
    Kanemasa, T
    Ninomiya, M
    Fujimoto, M
    Konoike, T
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (04) : 897 - 907
  • [2] Discovery of potent, soluble and orally active TRPV1 antagonists. Structure-activity relationships of a series of isoxazoles
    Ratcliffe, Paul
    Abernethy, Lynn
    Ansari, Nasrin
    Cameron, Ken
    Clarkson, Tom
    Dempster, Maureen
    Dunn, David
    Easson, Anna-Marie
    Edwards, Darren
    Everett, Katy
    Feilden, Helen
    Ho, Koc-Kan
    Kultgen, Steve
    Littlewood, Peter
    Maclean, John
    McArthur, Duncan
    McGregor, Deborah
    McLuskey, Hazel
    Neagu, Irina
    Nimz, Olaf
    Nisbet, Lesley-Anne
    Ohlmeyer, Michael
    Palin, Ronnie
    Pham, Quynhchi
    Rong, Yajing
    Roughton, Andrew
    Sammons, Melanie
    Swanson, Robert
    Tracey, Heather
    Walker, Glenn
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (15) : 4652 - 4657
  • [3] Design, synthesis, and structure-activity relationships of a series of novel N-aryl-2-phenylcyclopropanecarboxamide that are potent and orally active orexin receptor antagonists
    Yoshida, Yu
    Terauchi, Taro
    Naoe, Yoshimitsu
    Kazuta, Yuji
    Ozaki, Fumihiro
    Beuckmann, Carsten T.
    Nakagawa, Makoto
    Suzuki, Michiyuki
    Kushida, Ikuo
    Takenaka, Osamu
    Ueno, Takashi
    Yonaga, Masahiro
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (21) : 6071 - 6088
  • [4] Synthesis and structure-activity relationships of potent and orally active 5-HT4 receptor antagonists:: Indazole and benzimidazolone derivatives
    Schaus, JM
    Thompson, DC
    Bloomquist, WE
    Susemichel, AD
    Calligaro, DO
    Cohen, ML
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (11) : 1943 - 1955
  • [5] Highly selective endothelin antagonists for ET(A) receptor: Synthesis and structure-activity relationships
    Liu, G
    Henry, KJ
    Szczepankiewicz, BG
    Winn, M
    Boyd, SA
    Mantei, RA
    Wasicak, J
    vonGeldern, TW
    WuWong, JR
    Chiou, W
    Dixon, D
    Opgenorth, TJ
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1997, 213 : 193 - MEDI
  • [6] Molecular design and structure-activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664
    Das, J
    Kimball, SD
    Hall, SE
    Han, WC
    Iwanowicz, E
    Lin, J
    Moquin, RV
    Reid, JA
    Sack, JS
    Malley, MF
    Chang, CYY
    Chong, SH
    Wang-Iverson, DB
    Roberts, DGM
    Seiler, SM
    Schumacher, WA
    Ogletree, ML
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (01) : 45 - 49
  • [7] Structure-activity relationships in a series of orally active gamma-hydroxy butenolide endothelin antagonists
    Patt, WC
    Edmunds, JJ
    Repine, JT
    Berryman, KA
    Reisdorph, BR
    Lee, C
    Plummer, MS
    Shahripour, A
    Haleen, SJ
    Keiser, JA
    Flynn, MA
    Welch, KM
    Reynolds, EE
    Rubin, R
    Tobias, B
    Hallak, H
    Doherty, AM
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (07) : 1063 - 1074
  • [8] Structure-activity relationships of truncated adenosine derivatives as highly potent and selective human A3 adenosine receptor antagonists
    Pal, Shantanu
    Choi, Won Jun
    Choe, Seung Ah
    Heller, Cara L.
    Gao, Zhan-Guo
    Chinn, Moshe
    Jacobson, Kenneth A.
    Hou, Xiyan
    Lee, Sang Kook
    Kim, Hea Ok
    Jeong, Lak Shin
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (10) : 3733 - 3738
  • [9] Synthesis and structure-activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors
    Nagao, Satoshi
    Yamane, Yoshinobu
    Funasaka, Setsuo
    Tanaka, Keigo
    Miyazaki, Kazuki
    Kotake, Yoshihiko
    Kamata, Jun-ichi
    Watanabe-Miyano, Saori
    Toyama, Osamu
    Ozawa, Yoichi
    Mizui, Yoshiharu
    Okamoto, Kiyoshi
    Ito, Daisuke
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (19) : 5513 - 5529
  • [10] Synthesis and structure-activity relationship of ethenesulfonamide derivatives: Potent and orally active endothelin receptor antagonists.
    Harada, H
    Kazami, J
    Watanuki, S
    Tsuzuki, R
    Sudoh, K
    Tanaka, A
    Fujimori, A
    Tsukamoto, S
    Yanagisawa, I
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 221 : U10 - U10
12345