Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors

被引：33

作者：

Wang, YG ^{[1
]}

Chackalamannil, S ^{[1
]}

Hu, ZY ^{[1
]}

Boyle, CD ^{[1
]}

Lankin, CM ^{[1
]}

Xia, Y ^{[1
]}

Xu, R ^{[1
]}

Asberom, T ^{[1
]}

Pissarnitski, D ^{[1
]}

Stamford, AW ^{[1
]}

Greenlee, WJ ^{[1
]}

Skell, J ^{[1
]}

Kurowski, S ^{[1
]}

Vemulapalli, S ^{[1
]}

Palamanda, J ^{[1
]}

Chintala, M ^{[1
]}

Wu, P ^{[1
]}

Myers, J ^{[1
]}

Wang, P ^{[1
]}

机构：

[1] Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 21期

关键词：

D O I：

10.1016/S0960-894X(02)00646-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC50 = 0.6 nM, PDE6/PDE5 = 101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC50 = 3.5 nM, PDE6/PDE5 = 7). (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：3149 / 3152

页数：4

共 7 条

[1] The discovery of novel, potent and selective PDE5 inhibitors [J].

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

[2] Cyclic GMP phosphodiesterase-5: Target of sildenafil [J].

Corbin, JD ;

Francis, SH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (20) :13729-13732

[3] Novel in vivo procedure for rapid pharmacokinetic screening of discovery compounds in rats [J].

Cox, KA ;

Dunn-Meynell, K ;

Korfmacher, WA ;

Broske, L ;

Nomeir, AA ;

Lin, CC ;

Cayen, MN ;

Barr, WH .

DRUG DISCOVERY TODAY, 1999, 4 (05) :232-237

[4] Phosphodiesterase 5 inhibitors and nitrergic transmission - from zaprinast to sildenafil [J].

Gibson, A .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 411 (1-2) :1-10

[5] Sildenafil - A review of its use in erectile dysfunction [J].

Langtry, HD ;

Markham, A .

DRUGS, 1999, 57 (06) :967-989

[6] Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic, noncholinergic mechanism [J].

Vemulapalli, S ;

Kurowski, S .

FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2001, 15 (01) :1-7

[7] Characterization of human, dog and rabbit corpus cavernosum type 5 phosphodiesterases [J].

Wang, P ;

Wu, P ;

Myers, JG ;

Stamford, A ;

Egan, RW ;

Billah, MM .

LIFE SCIENCES, 2001, 68 (17) :1977-1987

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