Furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors for treatment of erectile dysfunction

被引:29
|
作者
Jiang, WQ [1 ]
Sui, ZH [1 ]
Macielag, MJ [1 ]
Walsh, SP [1 ]
Fiordeliso, JJ [1 ]
Lanter, JC [1 ]
Guan, JH [1 ]
Qiu, YH [1 ]
Kraft, P [1 ]
Bhattacharjee, S [1 ]
Craig, E [1 ]
Haynes-Johnson, D [1 ]
John, TM [1 ]
Clancy, J [1 ]
机构
[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ 08869 USA
关键词
D O I
10.1021/jm0202573
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Synthesis of furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors was reported. Their in vitro potencies in inhibiting PDE5 and selectivity in inhibiting other PDE isozymes (PDE1-4 and PDE6) were evaluated. Some of these compounds are more potent than sildenafil with better selectivity toward PDE1 and PDE6. Incorporation of solublizing groups resulted in bioavailable analogues. Selected compounds showed in vivo efficacy in anesthetized dog model for penile erection.
引用
收藏
页码:441 / 444
页数:4
相关论文
共 50 条
  • [21] The discovery of novel, potent and selective PDE5 inhibitors
    Bi, YZ
    Stoy, P
    Adam, L
    He, B
    Krupinski, J
    Normandin, D
    Pongrac, R
    Seliger, L
    Watson, A
    Macor, JE
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (18) : 2461 - 2464
  • [22] Psychological Predictors of PDE5 Inhibitors in Vasculogenic Erectile Dysfunction
    Palmas, Artur
    Pascoal, Patricia
    Nobre, Pedro
    INTERNATIONAL JOURNAL OF SEXUAL HEALTH, 2019, 31 : A568 - A568
  • [23] PDE5 INHIBITORS FAILURES IN ERECTILE DYSFUNCTION - WHAT ARE THE CAUSES?
    Fedorova, Anna
    Vykhodtcev, Sergei
    Lukyanov, Andrey
    JOURNAL OF SEXUAL MEDICINE, 2017, 14 (05): : E306 - E306
  • [24] PDE5 inhibitors: Is there more to come besides erectile dysfunction?
    Stief, Christian
    EUROPEAN UROLOGY, 2007, 52 (04) : 943 - 944
  • [25] Design, synthesis and biological evaluation of pyrazolopyrimidinone based potent and selective PDE5 inhibitors for treatment of erectile dysfunction (vol 89, 103022, 2019)
    Reddy, G. Lakshma
    Dar, Mohd. Ishaq
    Hudwekar, Abhinandan D.
    Mahajan, Priya
    Nargotra, Amit
    Baba, Adil Manzoor
    Nandi, Utpal
    Wazir, Priya
    Singh, Gurdarshan
    Bharate, Sonali S.
    Vishwakarma, Ram A.
    Syed, Sajad Hussain
    Sawant, Sanghapal D.
    BIOORGANIC CHEMISTRY, 2019, 92
  • [26] Selective N-pyrimidinyl pyrroloquinolone PDE5 inhibitors as agents for treatment of male erectile dysfunction.
    Jiang, WQ
    Sui, ZH
    Guan, JH
    Macielag, MJ
    Zhang, SY
    Qiu, YH
    Kraft, P
    Bhattacharjee, S
    Lombardi, E
    Haynes-Johnson, D
    John, TM
    Clancy, J
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 224 : U56 - U56
  • [27] Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED
    Boyle, CD
    Xu, R
    Asberom, T
    Chackalamannil, S
    Clader, JW
    Greenlee, WJ
    Guzik, H
    Hu, YQ
    Hu, ZY
    Lankin, CM
    Pissarnitski, DA
    Stamford, AW
    Wang, YG
    Skell, J
    Kurowski, S
    Vemulapalli, S
    Palamanda, J
    Chintala, M
    Wu, P
    Myers, J
    Wang, P
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (09) : 2365 - 2369
  • [28] Continuous use of PDE5 inhibitors in the treatment of erectile dysfunction: New insights and opportunities
    Maria Puigvert, Ana
    Prieto, Rafael
    Garcia, Ferran
    REVISTA INTERNACIONAL DE ANDROLOGIA, 2018, 16 (01): : 28 - 33
  • [29] B-carboline as PDE5 inhibitors for treatment of male erectile dysfunction.
    Guan, JH
    Jiang, WQ
    Sui, ZH
    Macielag, MJ
    Walsh, SP
    Lanter, JC
    Fiordeliso, JJ
    Alford, VC
    Qiu, YH
    Patricia, K
    Bhattacharjee, S
    Lombardi, E
    Haynes-Johnson, D
    John, TM
    Clancy, J
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 224 : U55 - U55
  • [30] Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors
    Zheng, Hongbo
    Li, Lin
    Sun, Bin
    Gao, Yun
    Song, Wei
    Zhao, Xiaoyu
    Gao, Yanhui
    Xie, Zhiyu
    Zhang, Nianzhao
    Ji, Jianbo
    Yuan, Huiqing
    Lou, Hongxiang
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 150 : 30 - 38