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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 03期

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

页码：441 / 444

页数：4

共 17 条

[1]

Bombrun A, 1997, Patent No, Patent No. [WO97/43287, 9743287]

[2] Sildenafil citrate (Viagra®) [J].

Brock, G .

DRUGS OF TODAY, 2000, 36 (2-3) :125-134

[3] Synthesis of a novel fused tricyclic quinolone system via oxidation of 1,2,3,4-tetrahydro-beta-carbolines. [J].

Carniaux, JF ;

KanFan, C ;

Royer, J ;

Husson, HP .

TETRAHEDRON LETTERS, 1997, 38 (17) :2997-3000

[4] EFFICIENCY IN PEPTIDE COUPLING - 1-HYDROXY-7-AZABENZOTRIAZOLE VS 3,4-DIHYDRO-3-HYDROXY-4-OXO-1,2,3-BENZOTRIAZINE [J].

CARPINO, LA ;

EL-FAHAM, A ;

ALBERICIO, F .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (11) :3561-3564

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

Corbin, JD ;

Francis, SH .

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

[6] BROP - A NEW REAGENT FOR COUPLING N-METHYLATED AMINO-ACIDS [J].

COSTE, J ;

DUFOUR, MN ;

PANTALONI, A ;

CASTRO, B .

TETRAHEDRON LETTERS, 1990, 31 (05) :669-672

[7] THE PICTET-SPENGLER CONDENSATION - A NEW DIRECTION FOR AN OLD REACTION [J].

COX, ED ;

COOK, JM .

CHEMICAL REVIEWS, 1995, 95 (06) :1797-1842

[8] IMPOTENCE AND ITS MEDICAL AND PSYCHOSOCIAL CORRELATES - RESULTS OF THE MASSACHUSETTS MALE AGING STUDY [J].

FELDMAN, HA ;

GOLDSTEIN, I ;

HATZICHRISTOU, DG ;

KRANE, RJ ;

MCKINLAY, JB .

JOURNAL OF UROLOGY, 1994, 151 (01) :54-61

[9]

JIANG W, 2002, 224 NAT M AM CHEM SO

[10] Drug therapy: Erectile dysfunction. [J].

Lue, TF .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (24) :1802-1813

← 1 2 →