19212-27-2Relevant articles and documents
A new β-keto amide synthesis
Chen, Yanping,Sieburth, Scott McN.
, p. 2191 - 2194 (2002)
In a modification of the Wierenga-Skulnick β-ketoester synthesis, the dianions of malonic acid mono-amides were condensed with acid chlorides. Acidic workup led to decarboxylation and isolation of the corresponding β-keto amides in good-to-excellent yield
Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Sharma, Niti,Kang, Jong Seong,Jung, Sang-Hun
, (2020/09/16)
To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
Electrophile-Directed Diastereoselective Oxonitrile Alkylations
Chepyshev, Sergiy V.,Pitta, Bhaskar Reddy,Vangala, Saidi Reddy,Lujan-Montelongo, J. Armando,Steward, Omar W.,Fleming, Fraser F.
supporting information, p. 2850 - 2853 (2018/02/09)
Diastereoselective alkylation of prochiral oxonitrile dianions with secondary alkyl halides efficiently installs two contiguous stereogenic centers. The confluence of nucleophilic trajectory and the electrophile chirality causes distinct steric differences that allow efficient discrimination for one of the six possible conformers. Numerous oxonitrile-derived dianions efficiently displace secondary alkyl halides propagating the electrophile chirality to efficiently install two contiguous tertiary centers. The prevalence of chiral, secondary electrophiles makes the interdigitated alkylation of chiral electrophiles a particularly attractive route because the resulting oxonitriles are readily transformed into bioactive heterocycles.
SULFONYLAMINOPYRIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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Page/Page column 98-99, (2016/01/25)
Provided are sulfonylaminopyridine compounds that are inhibitors of ITK kinase, compositions containing these compounds and methods for treating diseases mediated by ITK kinase. In particular, provided are compounds of Formula (I), (II) or (III), stereoisomers, tautomers, solvates, prodrugs or pharmaceutically acceptable salts thereof, where n, R1, R2, R3, R6 and R7 are defined herein, pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, for example, for treating a disease or condition mediated by ITK kinase in a patient.
