90993-50-3Relevant academic research and scientific papers
PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS
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Page/Page column 69, (2012/10/08)
Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)
AMINOTHIAZOLE DERIVATIVE
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Page/Page column 9, (2012/09/10)
A compound represented by formula (1) or a pharmaceutically acceptable salt thereof, which has a PI3 kinase 3 inhibitory effect and is useful as a prophylactic or therapeutic agent for articular rheumatism, Crohn''s disease, irritable colitis, Sjoegren''s syndrome, multiple sclerosis, systemic lupus erythematosus, asthma, atopic dermatitis, arteriosclerosis, organ transplant rejection, cancer, retinopathy, psoriasis, arthrosis deformans, age-related macular degeneration, type II diabetes, insulin resistance, obesity, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hyperlipemia, etc.
NOVEL 1,2,4 OXADIAZOLE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 71, (2009/12/28)
The invention relates to 1,2,4 oxadiazole compounds and analogs thereof, represented by formula (II), and compositions and methods of use thereof.
Novel aryl and heteroaryl substituted N-[3-(4-phenylpiperazin-1-yl)propyl]-1,2,4-oxadiazole-5-carboxamides as selective GSK-3 inhibitors
Koryakova, Angela G.,Ivanenkov, Yan A.,Ryzhova, Elena A.,Bulanova, Elena A.,Karapetian, Ruben N.,Mikitas, Olga V.,Katrukha, Eugeny A.,Kazey, Vasily I.,Okun, Ilya,Kravchenko, Dmitry V.,Lavrovsky, Yan V.,Korzinov, Oleg M.,Ivachtchenko, Alexandre V.
supporting information; experimental part, p. 3661 - 3666 (2009/04/16)
Synthesis, biological evaluation, and SAR dependencies for a series of novel aryl and heteroaryl substituted N-[3-(4-phenylpiperazin-1-yl)propyl]-1,2,4-oxadiazole-5-carboxamide inhibitors of GSK-3β kinase are described. The inhibitory activity of the synthesized compounds is highly dependent on the character of substituents in the phenyl ring and the nature of terminal heterocyclic fragment of the core molecular scaffold. The most potent compounds from this series contain 3,4-di-methyl or 2-methoxy substituents within the phenyl ring and 3-pyridine fragment connected to the 1,2,4-oxadiazole heterocycle. These compounds selectively inhibit GSK-3β kinase with IC50 value of 0.35 and 0.41 μM, respectively.
