ARGATROBAN ANALOGS - SYNTHESIS, THROMBIN INHIBITORY ACTIVITY AND CELL-PERMEABILITY OF AMINOHETEROCYCLIC GUANIDINE SURROGATES

Authors
MISRA RN KELLY YF BROWN BR ROBERTS DGM CHONG SH SEILER SM
Citation
Rn. Misra et al., ARGATROBAN ANALOGS - SYNTHESIS, THROMBIN INHIBITORY ACTIVITY AND CELL-PERMEABILITY OF AMINOHETEROCYCLIC GUANIDINE SURROGATES, Bioorganic & medicinal chemistry letters, 4(18), 1994, pp. 2165-2170
Citations number
14
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
4
Issue
18
Year of publication
1994
Pages
2165 - 2170
Database
ISI
SICI code
0960-894X(1994)4:18<2165:AA-STI>2.0.ZU;2-#
Abstract
A series of Argatroban analogs, 3-6, in which the guanidino group was replaced by amino-substituted heterocycles of decreasing basicity were prepared and evaluated for their ability to inhibit human alpha-throm bin. Basicity was found to be important in determining inhibitory pote ncy. Aminopyridine analog 3b (pK(a) similar to 7) afforded the most po tent inhibition (I(50)approximate to 0.47 mu M) and exhibited enhanced Caco-2 cell permeability.