1585971-57-8Relevant articles and documents
A novel domino reaction for the preparation of substituted non-racemic β-proline derivatives
Gilbert, Eric J.,Brunskill, Andrew,Cai, Jiaqiang,Cai, Yaxian,Chu, Xin-Jie,Dai, Xing,Hao, Jinsong,Kuethe, Jeffrey T.,Lai, Zhong,Liu, Hong,Mu, Cuizhi,Qi, Yan,Scott, Jack D.,Taoka, Brandon,Truong, Quang,Walsh, Shawn P.,Wu, Wen-Lian,Cumming, Jared N.
, p. 6011 - 6020 (2016)
A novel domino reaction for the preparation of non-racemic β-proline derivatives is reported. The addition of a methyl 2-(oxetan-3-yl)acetate titanium enolate to chiral tert-butanesulfinyl ketimines followed by an intramolecular oxetane ring-opening provi
Discovery of S3-Truncated, C-6 Heteroaryl Substituted Aminothiazine β-Site APP Cleaving Enzyme-1 (BACE1) Inhibitors
Wu, Yong-Jin,Guernon, Jason,Shi, Jianliang,Marcin, Lawrence,Higgins, Mendi,Rajamani, Ramkumar,Muckelbauer, Jodi,Lewis, Hal,Chang, Chiehying,Camac, Dan,Toyn, Jeremy H.,Ahlijanian, Michael K.,Albright, Charles F.,Macor, John E.,Thompson, Lorin A.
, p. 8593 - 8600 (2016/10/03)
Truncation of the S3 substituent of the biaryl aminothiazine 2, a potent BACE1 inhibitor, led to a low molecular weight aminothiazine 5 with moderate activity. Despite its moderate activity, compound 5 demonstrated significant brain Aβ reduction in rodents. The metabolic instability of 5 was overcome by the replacement of the 6-dimethylisoxazole, a metabolic soft spot, with a pyrimidine ring. Thus, truncation of the S3 substituent represents a viable approach to the discovery of orally bioavailable, brain-penetrant BACE1 inhibitors.
4,6-DIARYLAMINOTHIAZINES AS BACE1 INHIBITORS AND THEIR USE FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION
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Page/Page column 72; 73, (2014/07/08)
Compounds of formula (I), including pharmaceutically acceptable salts thereof, are set forth herein: (I) wherein R1 and R2 are independently hydrogen, or -CH3; or R1 and R2 can join together in a ring by adding -(CH2)4-; R3 is hydrogen or C1-C3 al-kyl; Y and Z are independently a C6-C10- aryl group or a 5-10 membered heterocyclic group which can be further substituted with from 0-3 substituents selected from the group of halogen, hydroxy, amino, C1-4 alkylamino, C1-4 dialkylamino, halo C1-4 alkyl, CN, C1-C6, alkyl or cycloalkyl, C1-C6 alkoxy, -C=OC1-4 alkyl, -SO2C1-4 alkyl, and C2-C4 alkynyl; A is selected from the group of phenyl, ben-zyl, oxazolyl, thiazolyl, isoxazolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, and pyrazinyl groups which can be further substituted with from 0-3 substituents selected from the group of halogen, hydroxy, amino, C1-4 alkylamino, C1-4 dialkylamino, haloC1-4 alkyl, hydroxyC1-6 alkyl, CN, C1-C6 alkyl or cycloalkyl, C1-C6 alkoxy, and C2-C4 alkynyl; L is -NHCO-, or is a single bond; and L and Z to-gether can be absent
