111292-75-2

Upstream product

• 625-35-4 trans-chrotonyl chloride 
• 99395-88-7 (S)-4-phenyl-2-oxazolidinone 
• 623-68-7 crotonic anhydride 
• 623-68-7 trans-crotonic anhydride 
• 20989-17-7 (2S)-2-phenylglycinol 
• 2935-35-5 (S)-2-phenylglycine 

Downstream Products

• 146137-33-9 (4S)-4-phenyl-3-(3-phenylbutanoyl)oxazolidin-2-one 
• 148706-31-4 (S)-3-((2S,3S)-2-Bromo-3-phenyl-butyryl)-4-phenyl-oxazolidin-2-one 
• 148706-33-6 (S)-3-[(2S,3S)-2-Bromo-3-(2,6-dimethyl-phenyl)-butyryl]-4-phenyl-oxazolidin-2-one 
• 112530-04-8 (4S)-3-((4'R,5'R)-1',5'-dimethylcyclohexene-4'-carbonyl)-4-phenyl-2-oxazolidinone 
• 112530-03-7 (4S)-3-((4'S,5'S)-1',5'-dimethylcyclohexene-4'-carbonyl)-4-phenyl-2-oxazolidinone 
• 142078-06-6 (4S)-3-(3-methyl-5-hexenoyl)-4-phenyl-2-oxazolidinone 
• 217961-50-7 (S)-3-(S)-3-methyl-6-(trimethylsilyl)hex-5-ynoyl-4-phenyloxazolidin-2-one 
• 216494-25-6 (S)-3-[(R)-6-(tert-Butyl-diphenyl-silanyloxy)-3-methyl-4-methylene-hexanoyl]-4-phenyl-oxazolidin-2-one 
• 306275-03-6 (S)-3-((3S,5S)-6-Benzyloxy-3,5-dimethyl-hexanoyl)-4-phenyl-oxazolidin-2-one 
• 619328-34-6 (4S,2'S,3'S,5'S)-3-(7'-benzyloxy-2',3',5'-trimethylheptanoyl)-4-phenyloxazolidin-2-one 
• 916771-63-6 3-[5-(tert-butyl-diphenyl-silanyloxymethyl)-3-methyl-hex-5-enoyl]-4-phenyl-oxazolidin-2-one 
• 148706-34-7 (S)-3-[(2S,3S)-2-Bromo-3-(4-methoxy-phenyl)-butyryl]-4-phenyl-oxazolidin-2-one 
• 151800-33-8 (3(2R,3S),4S)-3-<2-Azido-3-(4-methoxyphenyl)butyroyl>-4-phenyl-2-oxazolidinone 
• 148766-21-6 (S)-3-[(2R,3S)-2-Azido-3-(4-methoxy-2-methyl-phenyl)-butyryl]-4-phenyl-oxazolidin-2-one 

Relevant academic research and scientific papers

Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists

G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.

Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties ()

Cholesteryl ester transfer protein (CETP) represents one of the key regulators of the homeostasis of lipid particles, including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Epidemiological evidence correlates increased HDL and decreased LDL to coronary heart disease (CHD) risk reduction. This relationship is consistent with a clinical outcomes trial of a CETP inhibitor (anacetrapib) combined with standard of care (statin), which led to a 9% additional risk reduction compared to standard of care alone. We discuss here the discovery of MK-8262, a CETP inhibitor with the potential for being the best-in-class molecule. Novel in vitro and in vivo paradigms were integrated to drug discovery to guide optimization informed by a critical understanding of key clinical adverse effect profiles. We present preclinical and clinical evidence of MK-8262 safety and efficacy by means of HDL increase and LDL reduction as biomarkers for reduced CHD risk.

Nucleophilic halo-michael addition under lewis-base activation

A simple and general conjugate nucleophilic halogenation is presented. The THTO/halosilane combination has shown the ability to act as a nucleophilic halide source in the conjugate addition to a variety of Michael acceptors. In addition, a straightforward diastereoselective halogen installation using α,β-unsaturated acyloxazolidinones as platforms has been developed.

Visible light photocatalytic asymmetric synthesis of pyrrolo[1,2-: A] indoles via intermolecular [3+2] cycloaddition

The intermolecular diastereoselective and enantioselective synthesis of pyrrolo[1,2-a]indoles is developed through a [3+2] cycloaddition between silyl-indole derivatives and α,β-unsaturated N-acyl oxazolidinones by merging photocatalysis and Lewis acid catalysis.

Palladium-Catalyzed Diastereoselective Synthesis of 3-Arylbutanoic Acid Derivatives

The first palladium-catalyzed diastereoselective conjugate addition of arylboronic acids to chiral imides is reported. The catalytic system employing 4-tert-butyloxazolidin-2-one as the chiral auxiliary in a mixed solvent system of MeOH/H2O (1:3) under an air atmosphere provides the optically active 3-arylbutanoic acid derivatives in excellent yields with high diastereoselectivity.

Dihydropyrazole GPR40 modulators

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.

FUSED BICYCLIC OXAZOLIDINONE CETP INHIBITOR

Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis.

Oxazolidine-2-thiones and thiazolidine-2-thiones as nucleophiles in intermolecular michael additions

Conjugate addition of thiazolidinethiones and oxazolidinethiones to N-crotonylthiazolidinethiones and -oxazolidinethiones was observed in the presence of excess triethylamine in dichloromethane. The addition takes place by the nitrogen of the heterocycle

Doubly diastereoselective conjugate addition of enantiopure lithium amides to enantiopure N-enoyl oxazolidin-2-ones: A mechanistic probe

The doubly diastereoselective conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to a range of enantiopure N-enoyl oxazolidin-2-ones has been used as a mechanistic probe to determine that the reactive conformation is the anti-s-cis form. The β-amino carbonyl products resulting from these conjugate addition reactions are useful templates for further elaboration into an α,β,α-pseudotripeptide.

Large-scale synthesis of SB-462795, a cathepsin K inhibitor: the RCM-based approaches

Two stereoselective syntheses of SB-462795, a highly potent cathepsin K inhibitor, are described. Both routes feature a C5-C6 disconnection by ring closing metathesis to construct an azepane ring and are amenable to large-scale manufacturing.