Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives:: Novel series of PDE4 inhibitors

被引：27

作者：

Andrés, JI

Alonso, JM

Díaz, A

Fernández, J

Iturrino, L

Martínez, P

Matesanz, E

Freyne, EJ

Deroose, F

Boeckx, G

Petit, D

Diels, G

Megens, A

Somers, M

Van Wauwe, J

Stoppie, P

Cools, M

De Clerck, F

Peeters, D

de Chaffoy, D

机构：

[1] Janssen Cilag, Basic Res Ctr, Toledo 45007, Spain

[2] Janssen Res Fdn, B-2340 Beerse, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)00817-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：653 / 658

页数：6

共 20 条

[1]

BEAVO JA, 1994, MOL PHARMACOL, V46, P399

[2]

BENDER PE, 1991, Patent No. 9200968

[3] SYNTHESIS AND IN-VITRO PROFILE OF A NOVEL SERIES OF CATECHOL BENZIMIDAZOLES - THE DISCOVERY OF POTENT, SELECTIVE PHOSPHODIESTERASE TYPE-IV INHIBITORS WITH GREATLY ATTENUATED AFFINITY FOR THE [H-3] ROLIPRAM BINDING-SITE [J].

CHENG, JB ;

COOPER, K ;

DUPLANTIER, AJ ;

EGGLER, JF ;

KRAUS, KG ;

MARSHALL, SC ;

MARFAT, A ;

MASAMUNE, H ;

SHIRLEY, JT ;

TICKNER, JE ;

UMLAND, JP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (17) :1969-1972

[4] Biarylcarboxylic acids and -amides: Inhibition of phosphodiesterase type IV versus [H-3]rolipram binding activity and their relationship to emetic behavior in the ferret [J].

Duplantier, AJ ;

Biggers, MS ;

Chambers, RJ ;

Cheng, JB ;

Cooper, K ;

Damon, DB ;

Eggler, JF ;

Kraus, KG ;

Marfat, A ;

Masamune, H ;

Pillar, JS ;

Shirley, JT ;

Umland, JP ;

Watson, JW .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (01) :120-125

[5]

Dyke H J, 1999, Expert Opin Investig Drugs, V8, P1301, DOI 10.1517/13543784.8.9.1301

[6]

FREYNE EJ, 1999, Patent No. 9950262

[7]

IKESU S, 1995, Patent No. 07128824

[8]

Jacobitz S, 1996, MOL PHARMACOL, V50, P891

[9] Phosphodiesterase 4 in macrophages: Relationship between cAMP accumulation, suppression of cAMP hydrolysis and inhibition of [H-3]R-(-)-rolipram binding by selective inhibitors [J].

Kelly, JJ ;

Barnes, PJ ;

Giembycz, MA .

BIOCHEMICAL JOURNAL, 1996, 318 :425-436

[10]

KRISTINSSON H, 1999, Patent No. 9800408

← 1 2 →