1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally active thrombin inhibitors

J B Rewinkel; H Lucas; P J van Galen; A B Noach; T G van Dinther; A M Rood; A J Jenneboer; C A van Boeckel

doi:10.1016/s0960-894x(99)00069-4

1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally active thrombin inhibitors

Bioorg Med Chem Lett. 1999 Mar 8;9(5):685-90. doi: 10.1016/s0960-894x(99)00069-4.

Authors

J B Rewinkel¹, H Lucas, P J van Galen, A B Noach, T G van Dinther, A M Rood, A J Jenneboer, C A van Boeckel

Affiliation

¹ NV Organon, Scientific Development Group, Oss, The Netherlands.

PMID: 10201829
DOI: 10.1016/s0960-894x(99)00069-4

Abstract

Replacement of the highly basic benzamidine moiety of NAPAP by the moderately basic 1-aminoisoquinoline moiety resulted in thrombin inhibitors with improved selectivity towards trypsin and enhanced Caco-2 cell permeability.

MeSH terms

Administration, Oral
Anticoagulants / chemical synthesis*
Anticoagulants / chemistry
Anticoagulants / pharmacology
Benzamidines / chemistry
Caco-2 Cells / drug effects
Caco-2 Cells / physiology
Dipeptides / chemical synthesis*
Dipeptides / chemistry
Dipeptides / pharmacology
Drug Design
Humans
Isoquinolines / chemistry*
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology
Thrombin / antagonists & inhibitors*
Trypsin Inhibitors / chemical synthesis
Trypsin Inhibitors / chemistry
Trypsin Inhibitors / pharmacology

Substances

Anticoagulants
Benzamidines
Dipeptides
Isoquinolines
Piperidines
Trypsin Inhibitors
N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide
Thrombin
benzamidine
1-aminoisoquinoline