Derivatives of 4-amino-pyridine as selective thrombin inhibitors

被引：29

作者：

vonderSaal, W ^{[1
]}

Kucznierz, R ^{[1
]}

Leinert, H ^{[1
]}

Engh, RA ^{[1
]}

机构：

[1] MAX PLANCK INST BIOCHEM, D-82152 MARTINSRIED, GERMANY

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 10期

关键词：

D O I：

10.1016/S0960-894X(97)00210-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

During screening for novel thrombin inhibitors it was discovered that the il-aminopyridine derivative 1 inhibits human alpha-thrombin competitively and selectively. The 4-aminopyridine moiety itself is most likely the major determinant of the selectivity due to the increased hydrophobicity of the S1 pocket in thrombin compared to trypsin and plasmin. Optimization led to the selective thrombin inhibitor 14 with an inhibition constant, Ki of 70 nM. (C) 1997 Elsevier Science Ltd.

引用

页码：1283 / 1288

页数：6

共 50 条

[1] The potency of 4-amino-pyridine derived thrombin inhibitors depends of their lipophilicity
vonderSaal, W
Leinert, H
Stegmeier, KH
Engh, RA
THROMBOSIS AND HAEMOSTASIS, 1997, : P2025 - P2025
[2] SOME DERIVATIVES OF 4-AMINO-PYRIDINE AND 4-NITRO-PYRIDINE
ESSERY, JM
SCHOFIELD, K
JOURNAL OF THE CHEMICAL SOCIETY, 1960, (DEC): : 4953 - 4959
[3] EFFECT OF 4-AMINO-PYRIDINE ON MEMBRANE OF INSECT SINGLE AXON
PELHATE, M
HUE, B
PICHON, Y
CHANELET, J
COMPTES RENDUS HEBDOMADAIRES DES SEANCES DE L ACADEMIE DES SCIENCES SERIE D, 1974, 278 (22): : 2807 - 2809
[4] PHARMACOKINETICS AND PHARMACODYNAMICS OF 4-AMINO-PYRIDINE IN GUINEA-PIGS
CAPACIO, BR
CHANG, FCT
SPRIGGS, D
BYERS, CE
MATTHEWS, RL
FASEB JOURNAL, 1995, 9 (04): : A687 - A687
[5] THE TIME AND POTENTIAL DEPENDENCE OF THE 4-AMINO-PYRIDINE BLOCK OF DELAYED RECTIFIER CHANNELS
JOHANSSON, S
ARHEM, P
ACTA PHYSIOLOGICA SCANDINAVICA, 1986, 128 (01): : A19 - A19
[6] COMPARISON OF THE NEUROMUSCULAR AND CENTRAL EFFECTS OF 4-AMINO-PYRIDINE AND 3,4-DIAMINOPYRIDINE
FOLDES, FF
NAGASHIMA, H
OHTA, Y
CHAUDHRY, I
FEDERATION PROCEEDINGS, 1982, 41 (05) : 1721 - 1721
[7] (Piperidinylmethyl)boroglycine derivatives as selective inhibitors of thrombin.
Carini, DJ
Huang, PP
Wexler, RR
Alexander, RS
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1996, 211 : 130 - MEDI
[8] INCREASE OF LARGE INTRAMEMBRANOUS PARTICLES IN THE PRESYNAPTIC ACTIVE ZONE AFTER ADMINISTRATION OF 4-AMINO-PYRIDINE
TOKUNAGA, A
SANDRI, C
AKERT, K
BRAIN RESEARCH, 1979, 174 (02) : 207 - 219
[9] EFFECTS OF 4-AMINO-PYRIDINE ON NERVOUS-SYSTEM OF COCKROACH (PERIPLANETA-AMERICANA L)
PELHATE, M
HUE, B
CHANELET, J
COMPTES RENDUS DES SEANCES DE LA SOCIETE DE BIOLOGIE ET DE SES FILIALES, 1972, 166 (12): : 1598 - 1605
[10] ACTION OF 4-AMINO-PYRIDINE ON ISOLATED GIANT-AXON OF COCKROACH, PERIPLANETA-AMERICANA L
PELHATE, M
HUE, B
CHANELET, J
COMPTES RENDUS DES SEANCES DE LA SOCIETE DE BIOLOGIE ET DE SES FILIALES, 1974, 168 (01): : 27 - 34

← 1 2 3 4 5 →