367966-67-4

Upstream product

• 441067-49-8 (2S,4S)-4-hydroxypyrrolidine-2-carboxylic acid hydrochloride 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 367966-45-8 (2S,4S)-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1,2-pyrrolidinedicarboxylic acid 1-(1,1-dimethylethyl) 2-methyl ester 

Downstream Products

• 1448347-43-0 (2S,4S)-N-((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(3,5-difluorophenyl)-4-hydroxy-5-oxopyrrolidine-2-carboxamide 
• 180321-18-0 methyl (2S,4S)-4-hydroxy-5-oxopyrrolidine-2-carboxylate 
• 367966-54-9 (2S,4R)-5-Acetoxy-4-(4-chloro-naphthalen-1-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 367966-51-6 (2S,4R)-4-(4-Chloro-naphthalen-1-yloxy)-5-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 367966-46-9 (2S,4R)-4-(4-Chloro-naphthalen-1-yloxy)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 

Relevant academic research and scientific papers

Novel Tricyclic Pyroglutamide Derivatives as Potent RORγt Inverse Agonists Identified using a Virtual Screening Approach

Employing a virtual screening approach, we identified the pyroglutamide moiety as a nonacid replacement for the cyclohexanecarboxylic acid group which, when coupled to our previously reported conformationally locked tricyclic core, provided potent and selective RORγt inverse agonists. Structure-activity relationship optimization of the pyroglutamide moiety led to the identification of compound 18 as a potent and selective RORγt inverse agonist, albeit with poor aqueous solubility. We took advantage of the tertiary carbinol group in 18 to synthesize a phosphate prodrug, which provided good solubility, excellent exposures in mouse PK studies, and significant efficacy in a mouse model of psoriasis.

PROCESS FOR PREPARING 1-ARYLSULFONYL-PYRROLIDINE-2-CARBOXAMIDE TRANSIENT RECEPTOR POTENTIAL CHANNEL ANTAGONIST COMPOUNDS AND CRYSTALLINE FORMS THEREOF

The invention relates generally to methods of preparing 1-arylsulfonyl-pyrrolidine-2-carboxamide Transient Receptor Potential channel antagonist compounds of the following structure (I): (I) The invention further relates to solvate and co-crystal polymorphs of crystalline formula (I), and methods of preparation thereof.

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.

SULFONYL PYRIDYL TRP INHIBITORS

The invention is concerned with the compounds of formula I: (I) and pharmaceutically acceptable salts thereof where R1 is a substituted or unsubstituted phenyl or a fused bicyclic comprising a substituted or unsubstituted phenyl. In addition, t

Total Synthesis and Stereochemical Revision of the 2-Formylpyrrole Alkaloid Hemerocallisamine i

The first total synthesis of the 2-formylpyrrole alkaloid hemerocallisamine I is reported. The convergent synthesis features a key Maillard-Type condensation of a complex amine derived from cis-4-hydroxy-l-proline with a dihydropyranone, to directly furnish the 2-formylpyrrole ring system. The absolute configuration of hemerocallisamine I has been revised on the basis of optical rotation data obtained for the synthesized compound.

1-(HET)ARYLSULFONYL-(PYRROLIDINE OR PIPERIDINE)-2-CARBOXAMIDE DERIVATIVES AND THEIR USE AS TRPA1 ANTAGONISTS

The invention is concerned with the compounds of formula I and salts thereof and other compounds of formulas II-IX as disclosed herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formulas I-IX as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain or asthma.

SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS

The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

Chiral synthesis of (+)-febrifugine and (-)-isofebrifugine by means of samarium diiodide-promoted carbon-nitrogen bond cleavage reaction

(+)-Febrifugine, a potential anti-malarial piperidine alkaloid, was synthesized from (4S)-hydroxyproline methyl ester, stereoselectively, where a samarium diiodide-promoted carbon-nitrogen bond cleavage reaction was involved as a key reaction. A stereocon

Stereocontrolled synthesis of a potent antimalarial alkaloid, (+)-febrifugine

A novel and stereocontrolled synthetic path to a potential antimalarial piperidine alkaloid, (+)-febrifugine, was established by employing a reductive deamination of a proline derivative with samarium diiodide, as a key step. A novel and stereocontrolled

A convenient and high yield method to prepare 4-hydroxypyroglutamic acids

RuO2/NaIO4 oxidation of N-Boc-4-silyloxy and 4-acetoxy proline methyl esters under ethyl acetate/water biphase condition gave N-Boc-4-silyloxy and 4-acetoxy pyroglutamic acid derivatives in high yields. Desilylation with TBAF afforded both cis- and trans-N-Boc-methyl-4-hydroxy pyroglutamates.