258878-31-8Relevant articles and documents
Triazole derivatives
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, (2008/06/13)
The invention relates to a triazole derivative with an activity inhibiting glycine transporter and for use as a pharmaceutical drug, and a novel triazole derivative. The inventive triazole derivative has an excellent activity inhibiting glycine transporter and is useful as a therapeutic agent of dementia, schizophrenia, cognitive disorders, or cognitive disorders involved in various diseases such as Alzheimer disease, Parkinson's disease, or Huntington disease or the like, or spasm involved in diseases such as nerve degenerative diseases and cerebrovascular disorders, or the like. Particularly, the pharmaceutical drug is useful for the amelioration of learning disability of dementia and the like.
Synthesis and pharmacological evaluation of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the human vasopressin V1a receptor
Kakefuda, Akio,Suzuki, Takeshi,Tobe, Takahiko,Tsukada, Junko,Tahara, Atsuo,Sakamoto, Shuichi,Tsukamoto, Shin-ichi
, p. 2589 - 2598 (2007/10/03)
A series of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives were prepared and evaluated as selective antagonists for the human vasopressin V1A receptor. The compounds were examined for their affinity to the cloned human V1A receptor (hV1A) and selectivity vs the cloned human V2 receptor (hV2). By utilizing the structure-activity relationship on 4,4-difluoro-5-methylidene-2,3,4,5-tetrahydrobenzazepine derivatives as dual antagonists for the V1A and V2 receptors in our previous study, we found that substituting the methoxy group at the 2-position of the 4-phenyl ring with (4-methylpiperazin-1-yl)alkoxy moieties brought about marked improvement of both affinity to hV1A and selectivity vs hV2. Further introduction of a methyl group into the 6-position of the 4-phenyl ring resulted in additional improvement of selectivity. One particular compound, 5-(4-biphenyl)-3-methyl-4-{2-[6-(4-methyl-l-piperazinyl)-hexyloxy]phenyl} -1,2,4-triazole (19) showed potent affinity to hV1A with a Ki value of 1.04 nM and high selectivity with a 1700-fold selectivity vs hV2. We also found marked differences in the affinity of compounds in this series between the human and the rat receptors. Compound, 19 was further examined for its V1A receptor antagonist activity in rats. As a result, 19 demonstrated antagonist activities toward an arginine vasopressin-induced increase in diastolic blood pressure after intravenous or oral administration and long-lasting oral activity.