Discovery and biological evaluation of adamantyl amide 11β-HSD1 inhibitors

被引：43
|
作者：
Webster, Scott P.
Ward, Peter
Binnie, Margaret
Craigie, Eilidh
McConnell, Kirsty M. M.
Sooy, Karen
Vinter, Andy
Seckl, Jonathan R.
Walker, Brian R.
机构：
[1] Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci, Endocrinol Unit, Edinburgh EH16 4TJ, Midlothian, Scotland
[2] Cresset Biomol Discovery Ltd, Letchworth SG6 4ET, Herts, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 10期
基金：
英国惠康基金;
关键词：
metabolic syndrome; 11; beta-HSD1; beta-HSD2; inhibitor; adamantane; amide; diabetes; 11 beta-hydroxysteroid dehydrogenase; enzyme inhibition; HSD1;
D O I：
10.1016/j.bmcl.2007.02.057
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of adamantyl amide 11 beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11 beta-HSD1 over 11 beta-HSD2 and possess excellent cellular potency in human and murine 11 beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2838 / 2843
页数：6
相关论文
共 50 条
  • [1] Discovery and optimization of adamantyl carbamate inhibitors of 11β-HSD1
    Tice, Colin M.
    Zhao, Wei
    Krosky, Paula M.
    Kruk, Barbara A.
    Berbaum, Jennifer
    Johnson, Judith A.
    Bukhtiyarov, Yuri
    Panemangalore, Reshma
    Scott, Boyd B.
    Zhao, Yi
    Bruno, Joseph G.
    Howard, Lamont
    Togias, Jennifer
    Ye, Yuan-Jie
    Singh, Suresh B.
    McKeever, Brian M.
    Lindblom, Peter R.
    Guo, Joan
    Guo, Rong
    Nar, Herbert
    Schuler-Metz, Annette
    Gregg, Richard E.
    Leftheris, Katerina
    Harrison, Richard K.
    McGeehan, Gerard M.
    Zhuang, Linghang
    Claremon, David A.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (22) : 6725 - 6729
  • [2] Discovery of Adamantyl Ethanone Derivatives as Potent 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitors
    Su, Xiangdong
    Pradaux-Caggiano, Fabienne
    Thomas, Mark P.
    Szeto, Michelle W. Y.
    Halem, Heather A.
    Culler, Michael D.
    Vicker, Nigel
    Potter, Barry V. L.
    CHEMMEDCHEM, 2010, 5 (07) : 1026 - 1044
  • [3] Recent advances in the discovery of 11β-HSD1 inhibitors
    Boyle, Craig D.
    CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT, 2008, 11 (04) : 495 - 511
  • [4] Identification of adamantyl urea derivatives as novel and selective 11β-HSD1 inhibitors
    Fujiwara, Hiroaki
    Suda, Hitoshi
    Nishimura, Tamiki
    Nunami, Noriko
    Sato, Yasuhiro
    Negishi, Toru
    Hiramine, Yasushi
    Kohayakawa, Chie
    Horiuchi, Yoshihiro
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2014, 247
  • [5] The discovery of azepane sulfonamides as potent 11β-HSD1 inhibitors
    Neelamkavil, Santhosh F.
    Boyle, Craig D.
    Chackalamannil, Samuel
    Greenlee, William J.
    Zhang, Lili
    Terracina, Giuseppe
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (16) : 4563 - 4565
  • [6] The discovery of 2-anilinothiazolones as 11β-HSD1 inhibitors
    Yuan, Chester
    St. Jean, David J., Jr.
    Liu, Qingyian
    Cai, Lynn
    Li, Aiwen
    Han, Nianhe
    Moniz, George
    Askew, Ben
    Hungate, Randall W.
    Johansson, Lars
    Tedenborg, Lars
    Pyring, David
    Williams, Meredith
    Hale, Clarence
    Chen, Michelle
    Cupples, Rod
    Zhang, Jiandong
    Jordan, Steven
    Bartberger, Michael D.
    Sun, Yaxiong
    Emery, Maurice
    Wang, Minghan
    Fotsch, Christopher
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (22) : 6056 - 6061
  • [7] Discovery of orally active butyrolactam 11β-HSD1 inhibitors
    Yeh, Vince S. C.
    Kurukulasuriya, Ravi
    Fung, Steven
    Monzon, Katina
    Chiou, William
    Wang, Jiahong
    Stolarik, Deanne
    Imade, Hovis
    Shapiro, Robin
    Knourek-Segel, Victoria
    Bush, Eugene
    Wilcox, Denise
    Nguyen, Phong T.
    Brune, Michael
    Jacobson, Peer
    Link, J. T.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (21) : 5555 - 5560
  • [8] Synthesis and biological evaluation of heterocycle containing adamantane 11β-HSD1 inhibitors
    Yeh, Vince S. C.
    Patel, Jyoti R.
    Yong, Hong
    Kurukulasuriya, Ravi
    Fung, Steven
    Monzon, Katina
    Chiou, William
    Wang, Jiahong
    Stolarik, Deanne
    Imade, Hovis
    Beno, David
    Brune, Michael
    Jacobson, Peer
    Sham, Hing
    Link, J. T.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (20) : 5414 - 5419
  • [9] Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension
    Bauman, David R.
    Whitehead, Alan
    Contino, Lisa C.
    Cui, Jisong
    Garcia-Calvo, Margarita
    Gu, Xin
    Kevin, Nancy
    Ma, Xiuying
    Pai, Lee-yuh
    Shah, Kashmira
    Shen, Xiaolan
    Stribling, Sloan
    Zokian, Hratch J.
    Metzger, Joe
    Shevell, Diane E.
    Waddell, Sherman T.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (12) : 3650 - 3653
  • [10] Synthesis and biological evaluation of picolinamides as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
    Ryu, Je Ho
    Kim, Shinae
    Han, Hye Young
    Son, Hyun Joo
    Lee, Hyun Jung
    Shin, Young Ah
    Kim, Jae-Sun
    Park, Hyeung-geun
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (03) : 695 - 700
12345