A series of noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1 was investigated. While the amidrazone and the amine series displayed limited oral absorption, the amidine series demonstrated generally good oral absorption and strong antithrombotic activity; the single-digit picomolar K(i) achieved from this series is among the best yet reported. The present work highlights the benzamidine compound 11f (LB30812) that exhibits excellent overall profiles of potency, oral absorption and antithrombotic efficacy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0960-894x(02)00093-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Antitumor Activity of Some New 1-(8-fluoro-4-oxoquinolin-5-yl)amidrazones.
Curr Org Synth
July 2024
Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, 11942, Jordan.
Background: Hydrazonoyl chloride, accessible from the respective 5-amino-8-fluoro- 4-oxoquinoline-3-carboxylate, undergoes a reaction with sec-cyclic amines to generate N1-(1- ethyl-8-fluoro-4-oxoquinolin-5-yl)amidrazone carboxylates.
Introduction: A novel set of N1-(1-ethyl-8-fluoro-4-oxoquinolin-5-yl)amidrazone carboxylates (7a-h) incorporating N-piperazines or related congeners was synthesized interaction of the hydrazonoyl chloride (6), accessible from the respective 5-amino-8-fluoro-4-oxoquinoline-3-carboxylate, with the appropriate sec-cyclic amine. These new compounds were characterized by HNMR, C-NMR, and HRMS spectral data and screened for their anticancer activities.
Unprecedented synthesis of a 14-membered hexaazamacrocycle.
Beilstein J Org Chem
November 2023
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Ave., 119991 Moscow, Russian Federation.
The transformation of 3-[(ethoxymethylene)amino]-1-methyl-1-pyrazole-4-carbonitrile into the 14-membered macrocycle, 2,10-dimethyl-2,8,10,16-tetrahydrodipyrazolo[3,4-:3',4'-][1,2,4,8,9,11]hexaazacyclotetradecine-4,12-diamine, by the reaction with excess hydrazine under various conditions was studied in detail. The reaction proceeded through the initial formation of 4-imino-2-methyl-2,4-dihydro-5-pyrazolo[3,4-]pyrimidin-5-amine followed by dimerization to give the final macrocycle. A convenient synthesis of the latter starting from 4-imino-2-methyl-2,4-dihydro-5-pyrazolo[3,4-]pyrimidin-5-amine was developed.
View Article and Find Full Text PDFRegioselective formation of 1,2,4-triazoles by the reaction of amidrazones in the presence of diethyl azodicarboxylate and catalyzed by triethylamine.
Mol Divers
February 2019
Department of Chemistry, University of Helsinki, PO Box 55, A. I. Virtasen aukio 1, 00014, Helsinki, Finland.
A general method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of amidrazones with ethyl azodicarboxylate and triethylamine (Mitsunobu reagent) in EtOH. This highly regioselective one-pot process provides rapid access to highly diverse triazoles. The reaction was explained, based on Mitsunobu reagent oxidizing ethanol to acetaldehyde, which would then react with amidrazones to give the substituted 3-methyltriazoles.
View Article and Find Full Text PDFSynthesis and antitumor activities of some new N1-(flavon-6-yl)amidrazone derivatives.
Arch Pharm (Weinheim)
June 2014
Faculty of Science, Chemistry Department, The University of Jordan, Amman, Jordan.
A new series of N1-(flavon-6-yl)amidrazones were synthesized by reacting the hydrazonoyl chloride derived from 6-aminoflavone with the appropriate sec-cyclic amines. The antitumor activities of these compounds were evaluated on breast cancer (MCF-7) and leukemic (K562) cell lines. Among the compounds tested, the N-morpholine derivative was the most active against the MCF-7 and K562 cell lines, with IC50 values of 5.
View Article and Find Full Text PDFAmidrazone complexes from a cascade platinum(II)-mediated reaction between amidoximes and dialkylcyanamides.
Inorg Chem
June 2013
Department of Chemistry, Saint Petersburg State University, Universitetsky Pr. 26, 198504 Stary Petergof, Russian Federation.
The aryl amidoximes R'C6H4C(NH2)═NOH (R' = Me, 2a; H, 2b; CN, 2c; NO2, 2d) react with the dialkylcyanamide platinum(II) complexes trans-[PtCl2(NCNAlk2)2] (Alk2 = Me2, 1a; C5H10, 1b) in a 1:1 molar ratio in CHCl3 to form chelated mono-addition products [3a-h]Cl, viz. [PtCl(NCNAlk2){NH═C(NR2)ON═C(C6H4R')NH2}]Cl (Alk2 = Me2; R' = Me, a; H, b; CN, c; NO2, d; Alk2 = C5H10; R' = Me, e; H, f; CN, g; NO2, h). In the solution, these species spontaneously transform to the amidrazone complexes [PtCl2{NH═C(NR2)NC(C6H4R')NNH2}] (7a-h; 36-47%); this conversion proceeds more selectively (49-60% after column chromatography) in the presence of the base (PhCH2)3N.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!