185320-06-3

Basic information

• Product Name: Proline, 4-hydroxy-5-oxo-, methyl ester (9CI)
• Synonyms: Proline, 4-hydroxy-5-oxo-, methyl ester (9CI);4-hydroxy-5-oxo-Proline Methyl ester
• CAS NO: 185320-06-3
• Molecular Formula: C6H9NO4
• Molecular Weight: 159.13996
• Product Categories: PYRROLE;CARBOXYLICESTER
• Mol File: 185320-06-3.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Proline, 4-hydroxy-5-oxo-, methyl ester (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: Proline, 4-hydroxy-5-oxo-, methyl ester (9CI)(185320-06-3)
• EPA Substance Registry System: Proline, 4-hydroxy-5-oxo-, methyl ester (9CI)(185320-06-3)

Safety Data

• Hazardous Substances Data: 185320-06-3(Hazardous Substances Data)

Upstream product

• 267420-70-2 1-(tert-butyl) 2-methyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-5-oxopyrrolidine-1,2-dicarboxylate 
• 367966-67-4 1-(tert-butyl) 2-methyl (2S,4S)-4-((tert-butyldimethylsilyl)oxy)-5-oxopyrrolidine-1,2-dicarboxylate 
• 400626-57-5 4-tert-butoxycarbonyloxy-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 180321-18-0 (2S,4R)-4-Hydroxy-5-oxo-pyrrolidine-2-carboxylic acid methyl ester 

Downstream Products

• 185320-06-3 (2S,4S)-4-Hydroxy-5-oxo-pyrrolidine-2-carboxylic acid methyl ester 

Relevant articles and documents

Tricyclic-Carbocyclic RORγt Inverse Agonists - Discovery of BMS-986313

SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound 1 (BMS-986251) led to tricyclic-carbocyclic analogues represented by 3-7 and culminated in the identification of 3d (BMS-986313), with structural differences distinct from 1. The X-ray co-crystal structure of 3d with the ligand binding domain of RORγt revealed several key interactions, which are different from 1. The in vitro and in vivo PK profiles of 3d are described. In addition, we demonstrate robust efficacy of 3d in two preclinical models of psoriasis - the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with 3d in these models is comparable to the results observed with 1.

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.

TRICYCLIC SULFONES AS ROR GAMMA MODULATORS

There are described RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

4-Substituted D-glutamic acid analogues: The first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity

The first potent inhibitors of glutamate racemase (MurI) enzyme that show whole cell antibacterial activity are described. Optically pure 4-substituted D-glutamic acid analogues with (2R,4S) stereochemistry and bearing aryl-, heteroaryl-, cinnamyl-, or biaryl-methyl substituents represent a novel class of glutamate racemase inhibitors. Exploration of the D-Glu core led to the identification of lead compounds (-)-8 and 10. 2-Naphthylmethyl derivative 10 was found to be a potent competitive inhibitor of glutamate racemase activity (Ki = 16 nM, circular dichroism assay; IC50 = 0.1 μg/mL high-performance liquid chromatography (HPLC) assay). Thorough structure-activity relationship (SAR) studies led to benzothienyl derivatives such as 69 and 74 with increased potency (IC50 = 0.036 and 0.01 μg/mL, respectively, HPLC assay). These compounds showed potent whole cell antibacterial activity against S. pneumoniae PN-R6, and good correlation with the enzyme assay. Compounds 69, 74 and biaryl derivative 52 showed efficacy in an in vivo murine thigh infection model against Streptococcus pneumoniae. Data described herein suggest that glutamate racemase may be a viable target for developing new antibacterial agents.

EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS

The present invention provides novel compounds that affect excitatory amino acid receptors and are useful in the treatment of neurological disorders. This invention also provides synthetic methods for the preparation of the novel compounds.