- Asymmetric synthesis of an antagonist of neurokinin receptors: SSR 241586
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SSR 241586 is a 2,2-disubstituted morpholine, developed by Sanofi-Aventis, which is active in the treatment of schizophrenia and irritable bowel syndrome (IBS). Different strategies have been studied to synthesize this molecule and among the strategies an
- Metro, Thomas-Xavier,Cochi, Anne,Gomez Pardo, Domingo,Cossy, Janine
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experimental part
p. 2594 - 2602
(2011/06/20)
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- Highly selective tripeptide thrombin inhibitors
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Tripeptide aldehydes such as Boc-D-Phe-Pro-Arg-H (5l) exhibit potent direct inhibition of thrombin. This distinction offers important insight for the design of more potent and selective serine protease inhibitors which may be useful pharmacological tools and hold promise for development of clinically useful agents. The structure-activity relationships (SAR) on a series of anticoagulant peptides with high selectivity for the enzyme thrombin are discussed. The SAR is centered on a series of di- and tripeptide arginine aldehydes based on the structure of 5l. The structural and conformational role of the amino acid residue in position 1 was investigated by substitution with conformationally restricted aromatic amino acids, aromatic acids, and a dipeptide isostere containing the ψ[CH2N] amide bond replacement. Many of these peptides demonstrate potent antithrombotic activity along with selectivity toward thrombin, determined by comparison of in vitro inhibitory effects on trypsin, plasmin, factor Xa, and tissue plasminogen activator. Compound 5f, D-1-Tiq-Pro-Arg-H · sulfate is highly active and the most selective tripeptide aldehyde inhibitor of thrombin reported to date.
- Shuman,Rothenberger,Campbell,Smith,Gifford-Moore,Gesellchen
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p. 314 - 319
(2007/10/02)
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- 1-Aryl-N2-alkyl-ethanediamines as isosters of adrenergic arylethanolamines.
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A family of 1-aryl-N2-alkyl-ethanediamines 1 isosteric with the N-alkyl-arylethanolamines are described. Although the prepared compounds were generally less potent than the N-alkyl-arylethanolamines, the 1-aryl-N'-(phenylmethyl)-N-alkyl-1,2-ethanediamines derivatives 6, are more active than the debenzylated free amino analogs 1, which may be indicative of the importance of the lipophilicity of the substituent at the alpha position to the aromatic ring.
- Berger,Nudelman
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p. 229 - 233
(2007/10/02)
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