149691-82-7Relevant articles and documents
Synthesis and Structure-Activity Relationships of 1-Acyl-4-(2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF Antagonists
Carceller, Elena,Merlos, Manuel,Giral, Marta,Almansa, Carmen,Bartroli, Javier,et al.
, p. 2984 - 2997 (2007/10/02)
A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines, with increased oral activity was prepared and evaluated in vitro in PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP).Oral activity was ascertained through a PAF-induced mortality test in mice (MOR).Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test.Three different types of acylsubstituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups.The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 μM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR-12519, PAG IC50 = 0.041 μM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086.Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests.On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.
(2-Alkyl-3-pyridyl)methylpiperazine derivatives as PAF antagonists
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, (2008/06/13)
The present invention relates to new (2-alkyl-3-pyridyl) methylpiperazine derivatives of general formula I: wherein R1, R2 and Z are as defined in Claim 1. The invention also relates to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent, orally active PAF antagonists and, consequently, they are useful in the treatment of the diseases in which this substance is involved.
