von der Saal, Wolfgang and Engh, Richard A. and Eichinger, Andreas and Gabriel, Bernhard and Kucznierz, Ralf and Sauer, Jürgen (1996) Syntheses and selective inhibitory activities of terphenyl-bisamidines for serine proteases. ARCHIV DER PHARMAZIE, 329 (2). pp. 73-82. ISSN 0365-6233, 1521-4184
Full text not available from this repository.Abstract
Biphenyl nitriles 5a-c, terphenyl dinitriles 11a-d, and naphthalene-bis(benzonitrile) 11e were prepared by palladium-catalyzed cross coupling reactions and subsequently converted to biphenyl amidines 8a-c and bis(benzamidines) 4a-e. Among the biphenyl amidines 8 only the meta-derivative 8b inhibits factor Xa and trypsin (K-i = 10 mu M). The terphenyl bisamidine 4c does not inhibit factor Xa, trypsin, thrombin, and plasmin, while 4a and 4d are almost equipotent inhibitors of these enzymes (K-i 1-6 mu M), and 4b and 4e are selective for trypsin (K-i = 0.2 and 0.3 mu M; but K-i > 1 mu M for factor Xa, thrombin, and plasmin). X-ray analysis of crystals of 4b complexed with bovine trypsin revealed a unique binding mode: one benzamidino group binds in the S1 site to the side chain carboxylate of Arg189. The central phenyl group is twisted away from the S2/S3 sites and the second amidino group contacts the Asn143 side chain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN ALPHA-THROMBIN; FACTOR-XA; ACID; BENZAMIDINE; DERIVATIVES; CONVERSION; blood-coagulation inhibitors; trypsin inhibitors; Suzuki coupling; Stille coupling |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Nov 2023 07:47 |
| Last Modified: | 14 Nov 2023 07:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/51949 |
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