Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 2: Optimization of 5,8-disubstituted derivatives

被引：31

作者：

Bernardelli, P

Lorthiois, E

Vergne, F

Oliveira, C

Mafroud, AK

Proust, E

Pham, N

Ducrot, P

Moreau, F

Idrissi, M

Tertre, A

Bertin, B

Coupe, M

Chevalier, E

Descours, A

Berlioz-Seux, F

Berna, P

Li, M

机构：

[1] Pfizer, Global Res & Dev, F-94265 Fresnes, France

[2] Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 18期

关键词：

PDE7; phosphodiesterase; pharmacokinetic; ADME;

D O I：

10.1016/j.bmcl.2004.07.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimization of 5,8-disubstituted spirocyclohexane-quinazolinones into potent, selective, soluble PDE7 inhibitors with acceptable in vivo pharmacokinetic parameters is presented. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4627 / 4631

页数：5

共 24 条

[1] Synthesis and structure-activity relationships of guan analogues as phosphodiesterase 7 (PDE7) inhibitors [J].

Barnes, MJ ;

Cooper, N ;

Davenport, RJ ;

Dyke, HJ ;

Galleway, FP ;

Galvin, FCA ;

Gowers, L ;

Haughan, AF ;

Lowe, C ;

Meissner, JWG ;

Montana, JG ;

Morgan, T ;

Picken, CL ;

Watson, RJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (08) :1081-1083

[2] CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES - FUNCTIONAL IMPLICATIONS OF MULTIPLE ISOFORMS [J].

BEAVO, JA .

PHYSIOLOGICAL REVIEWS, 1995, 75 (04) :725-748

[3]

BERNARDELLI P, 2002, Patent No. 0276954

[4] CoMFA of benzyl derivatives of 2,1,3-benzo and benzothieno[3,2-a]thiadiazine 2,2-dioxides:: clues for the design of phosphodiesterase 7 inhibitors [J].

Castro, A ;

Abasolo, MI ;

Gil, C ;

Segarra, V ;

Martinez, A .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (04) :333-338

[5]

Conti M, 2000, PRINCIPLES OF MOLECULAR REGULATION, P261

[6] INTERDEPENDENCE BETWEEN PHYSICAL PARAMETERS AND SELECTION OF SUBSTITUENT GROUPS FOR CORRELATION STUDIES [J].

CRAIG, PN .

JOURNAL OF MEDICINAL CHEMISTRY, 1971, 14 (08) :680-&

[7] THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].

DEWAR, MJS ;

ZOEBISCH, EG ;

HEALY, EF ;

STEWART, JJP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909

[8] 3 SYNTHETIC ROUTES TO A STERICALLY HINDERED TETRAZOLE - A NEW ONE-STEP MILD CONVERSION OF AN AMIDE INTO A TETRAZOLE [J].

DUNCIA, JV ;

PIERCE, ME ;

SANTELLA, JB .

JOURNAL OF ORGANIC CHEMISTRY, 1991, 56 (07) :2395-2400

[9]

Francis SH, 2001, PROG NUCLEIC ACID RE, V65, P1

[10]

KLUXEN FW, 2001, Patent No. 0183772

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