1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally active thrombin inhibitors.
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.
Rewinkel
J B
JB
NV Organon, Scientific Development Group, Oss, The Netherlands.
Lucas
H
H
van Galen
P J
PJ
Noach
A B
AB
van Dinther
T G
TG
Rood
A M
AM
Jenneboer
A J
AJ
van Boeckel
C A
CA
D000284:Administration, Oral; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001550:Benzamidines / Q000737:chemistry; D018938:Caco-2 Cells / Q000187:drug effects / Q000502:physiology; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000925:Anticoagulants; D001550:Benzamidines; D004151:Dipeptides; D007546:Isoquinolines; D010880:Piperidines; D014361:Trypsin Inhibitors; C038708:N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide; D013917:Thrombin; C032157:benzamidine; C041545:1-aminoisoquinoline