1263868-30-9Relevant academic research and scientific papers
Enantioselective Synthesis of a γ-Secretase Modulator via Vinylogous Dynamic Kinetic Resolution
Strotman, Neil A.,Ramirez, Antonio,Simmons, Eric M.,Soltani, Omid,Parsons, Andrew T.,Fan, Yu,Sawyer, James R.,Rosner, Thorsten,Janey, Jacob M.,Tran, Kristy,Li, Jun,La Cruz, Thomas E.,Pathirana, Charles,Ng, Alicia T.,Deerberg, Joerg
, p. 11133 - 11144 (2018)
Two efficient asymmetric routes to γ-secretase modulator BMS-932481, under investigation for Alzheimer's disease, have been developed. The key step for the first route involves a challenging enantioselective hydrogenation of an unfunctionalized trisubstituted alkene to establish the benzylic stereocenter, representing a very rare case of achieving high selectivity on a complex substrate. The second route demonstrates the first example of a vinylogous dynamic kinetic resolution (VDKR) ketone reduction, where the carbonyl and the racemizable stereocenter are not contiguous, but are conjugated through a pyrimidine ring. Not only did this transformation require both catalyst and substrate control to correctly establish the two stereocenters, but it also necessitated that the nonadjacent benzylic center of the ketone substrate be more acidic than that of the alcohol product to make the process dynamic. DFT computations aided the design of this novel VDKR pathway by reliably predicting the relative acidities of the intermediates involved.
Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481
Boy, Kenneth M.,Guernon, Jason M.,Zuev, Dmitry S.,Xu, Li,Zhang, Yunhui,Shi, Jianliang,Marcin, Lawrence R.,Higgins, Mendi A.,Wu, Yong-Jin,Krishnananthan, Subramaniam,Li, Jianqing,Trehan, Ashok,Smith, Daniel,Toyn, Jeremy H.,Meredith, Jere E.,Burton, Catherine R.,Kimura, S. Roy,Zvyaga, Tatyana,Zhuo, Xiaoliang,Lentz, Kimberley A.,Grace, James E.,Denton, Rex,Morrison, John S.,Mathur, Arvind,Albright, Charles F.,Ahlijanian, Michael K.,Olson, Richard E.,Thompson, Lorin A.,Macor, John E.
, p. 312 - 317 (2019/03/08)
A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine γ-secretase modulator BMS-932481. The compound showed robust reductions of Aβsub
COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION
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, (2012/02/02)
Compounds of the formula (I) are provided, including pharmaceutically acceptable salts thereof: which modulate β-amyloid peptide (β-AP) production, and are useful in the treatment of Alzheimer's Disease and other conditions affected by -amyloid peptide (β-AP) production.
COMPOUNDS FOR THE REDUCTION OF β-AMYLOID PRODUCTION
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, (2012/08/08)
The present disclosure provides a series of compounds of the formula (I), which modulate β-amyloid peptide (β-ΑΡ) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-ΑΡ) production.
COMPOUNDS FOR THE REDUCTION OF β-AMYLOID PRODUCTION
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, (2011/02/24)
The present disclosure provides a series of compounds of the formula (I) which modulate β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by β-amyloid peptide (β-AP) production.
