193538-79-3Relevant articles and documents
A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing
Cheung, Peter K.,Horhant, David,Bandy, Laura E.,Zamiri, Maryam,Rabea, Safwat M.,Karagiosov, Stoyan K.,Matloobi, Mitra,McArthur, Steven,Harrigan, P. Richard,Chabot, Benoit,Grierson, David S.
, p. 1869 - 1879 (2016/03/22)
A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics"of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 μM, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC50's ranging from 0.9 to 1.5 μM. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 μM, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.
Copper-mediated hydroxylation of arenes and heteroarenes directed by a removable bidentate auxiliary
Li, Xin,Liu, Yan-Hua,Gu, Wen-Jia,Li, Bo,Chen, Fa-Jie,Shi, Bing-Feng
supporting information, p. 3904 - 3907 (2014/08/18)
A copper-mediated C-H hydroxylation of arenes and heteroarenes using our newly developed PIP directing group has been developed. This procedure is scalable and compatible with a wide range of functional groups and heteroarenes, providing an operationally simple protocol for the synthesis of o-hydroxybenzamides. The hydroxylation of nicotinamides gave 4-oxo-1,4-dihydropyridine-3-carboxamides selectively. Preliminary mechanistic studies implicate that a basic ligand-enabled, irreversible, rate-determining CMD step is most likely involved in this process.
NEW COMPOUNDS 578
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Page/Page column 18, (2010/06/13)
The present invention relates to novel compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Downs syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer Disease, memory loss, attention deficit symptoms associated with Alzheimer disease, neurodegeneration associated with diseases such as Alzheimer disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
4-Pyridylanilinothiazoles that selectively target von Hippel - Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
Hay, Michael P.,Turcotte, Sandra,Flanagan, Jack U.,Bonnet, Muriel,Chan, Denise A.,Sutphin, Patrick D.,Nguyen, Phuong,Giaccia, Amato J.,Denny, William A.
supporting information; experimental part, p. 787 - 797 (2010/07/05)
Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel-Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure-activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different chemical features to potency illustrates a region, adjacent to the pyridyl ring, with potential for further development. Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC. 2009 American Chemical Society.
HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT
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Page/Page column 152-153, (2009/10/22)
Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.
