NONPEPTIDIC INHIBITORS OP NEUTRAL ENDOPEPTIDASE-24.11 .2. DESIGN AND PHARMACOLOGY OF ORALLY-ACTIVE PHOSPHONATE PRODRUGS

被引：18

作者：

DELOMBAERT, S

BLANCHARD, L

BERRY, C

GHAI, RD

TRAPANI, AJ

机构：

[1] Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 02期

关键词：

D O I：

10.1016/0960-894X(94)00475-U

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Prodrugs of 1 (CGS 26303), a novel non-peptidic neutral endopeptidase (NEP 24.11) inhibitor, have been designed. In particular, the diphenylphosphonate 6 (CGS 26393) was found to be a potent, orally bioavailable and long-acting NEP inhibitor. Accordingly, 6 protected atrial natriuretic peptide from enzymatic degradation and displayed a significant antihypertensive activity in the DOCA-salt rat.

引用

收藏

页码：151 / 154

页数：4

相关论文

共 8 条

[1] CHEMICAL AND PLASMA HYDROLYZES OF A DIPHENYL ALPHA-AMINOMETHYL PHOSPHONATE PRODRUG INHIBITOR OF NEUTRAL ENDOPEPTIDASE-24.11 [J].

DELOMBAERT, S ;

SINGH, K ;

BLANCHARD, L ;

SOLIMAN, VF .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (07) :899-902

[2] N-PHOSPHONOMETHYL DIPEPTIDES AND THEIR PHOSPHONATE PRODRUGS, A NEW-GENERATION OF NEUTRAL ENDOPEPTIDASE (NEP,EC-3.4.24.11) INHIBITORS [J].

DELOMBAERT, S ;

ERION, MD ;

TAN, J ;

BLANCHARD, L ;

ELCHEHABI, L ;

GHAI, RD ;

SAKANE, Y ;

BERRY, C ;

TRAPANI, AJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (04) :498-511

[3]

DELOMBAERT S, 1995, BIOORG MED CHEM LETT

[4]

DLOMBAERT S, 1994, BIOCHEM BIOPH RES CO, V204, P407

[5] PREPARATION OF 5-TETRAZOLYL GROUPS FROM CARBOXYLIC-ACIDS - SEQUENCE AMENABLE TO SENSITIVE SUBSTRATES [J].

FAUBL, H .

TETRAHEDRON LETTERS, 1979, (06) :491-494

[6]

GHAI RD, 1994, FASEB J, V8, pA99

[7] INTRAMOLECULAR PARTICIPATION OF THE AMIDE GROUP IN ACID-CATALYZED AND BASE-CATALYZED PHOSPHONATE MONOESTER HYDROLYSIS [J].

RAHIL, J ;

PRATT, RF .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1991, (07) :947-950

[8] PHARMACOLOGICAL PROFILE OF CGS-24128, A POTENT, LONG-ACTING INHIBITOR OF NEUTRAL ENDOPEPTIDASE-24.11 [J].

TRAPANI, AJ ;

BELL, ME ;

COTE, DT ;

DELOMBAERT, S ;

ERION, MD ;

GERLOCK, TE ;

GHAI, RD ;

HOPKINS, MF ;

PEPPARD, JV ;

WEBB, RL ;

LAPPE, RW ;

WORCEL, M .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 23 (03) :358-364