N-3-substituted imidazoquinazolinones: Potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction

被引：48

作者：

Rotella, DP ^{[1
]}

Sun, Z ^{[1
]}

Zhu, YH ^{[1
]}

Krupinski, J ^{[1
]}

Pongrac, R ^{[1
]}

Seliger, L ^{[1
]}

Normandin, D ^{[1
]}

Macor, JE ^{[1
]}

机构：

[1] Bristol Myers Squibb Pharmaceut Res Inst, Discovery Chem & Cardiovasc Drug Discovery, Princeton, NJ 08543 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2000年 / 43卷 / 07期

关键词：

D O I：

10.1021/jm000081+

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphodiesterase type 5 (PDE5) inhibitors with improved PDE isozyme selectivity relative to sildenafil may result in agents for the treatment of male erectile dysfunction (MED) with a lower incidence of PDE-associated adverse effects. This paper describes the discovery of 14, a PDE5 inhibitor with improved potency and selectivity in vitro compared to sildenafil. This compound shows activity in a functional assay of erectile function comparable to that of sildenafil.

引用

页码：1257 / 1263

页数：7

共 12 条

[1] CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES - FUNCTIONAL IMPLICATIONS OF MULTIPLE ISOFORMS
BEAVO, JA
[J]. PHYSIOLOGICAL REVIEWS, 1995, 75 (04) : 725 - 748
[2] BELL AS, Patent No. 5426107
[3] Boolell M, 1996, Int J Impot Res, V8, P47
[4] NITRIC-OXIDE IS A POTENT RELAXANT OF HUMAN AND RABBIT CORPUS CAVERNOSUM
BUSH, PA
ARONSON, WJ
BUGA, GM
RAJFER, J
IGNARRO, LJ
[J]. JOURNAL OF UROLOGY, 1992, 147 (06) : 1650 - 1655
[5] Eardley I, 1997, Expert Opin Investig Drugs, V6, P1803, DOI 10.1517/13543784.6.12.1803
[6] Drugs for the treatment of impotence
GarciaReboll, L
Mulhall, JP
Goldstein, I
[J]. DRUGS & AGING, 1997, 11 (02) : 140 - 151
[7] SELECTIVE-INHIBITION OF CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES OF HUMAN, BOVINE AND RAT AORTA
LUGNIER, C
SCHOEFFTER, P
LEBEC, A
STROUTHOU, E
STOCLET, JC
[J]. BIOCHEMICAL PHARMACOLOGY, 1986, 35 (10) : 1743 - 1751
[8] The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo
Stief, CG
Ückert, S
Becker, AJ
Truss, MC
Jonas, U
[J]. JOURNAL OF UROLOGY, 1998, 159 (04) : 1390 - 1393
[9] Sildenafil (VIAGRA(TM)), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction
Terrett, NK
Bell, AS
Brown, D
Ellis, P
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (15) : 1819 - 1824
[10] Phosphodiesterase inhibitors in the treatment of erectile dysfunction
Truss, MC
Stief, CG
[J]. DRUGS OF TODAY, 1998, 34 (09): : 805 - 812

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