41563-94-4

Usage

Derived from

Amino acid proline

Common use

Synthesis of pharmaceuticals and other organic compounds

Applications

Medicinal chemistry, due to its ability to form stable derivatives and unique chemical structure

Potential properties

Suitable for synthesis of biologically active molecules

Physical state

White crystalline solid at room temperature

Solubility

Soluble in water

Laboratory applications

Useful for a variety of laboratory applications due to its solubility and chemical properties

Versatility

Potential uses in various industries, particularly in the synthesis of pharmaceuticals

InChI:InChI=1/C8H10N2O3/c9-4-1-5-10-6(8(12)13)2-3-7(10)11/h6H,1-3,5H2,(H,12,13)

Upstream product

• 90243-80-4 N-(2-cyano-ethyl)-L-glutamic acid 
• 56-86-0 L-glutamic acid 
• 107-13-1 acrylonitrile 

Downstream Products

• 57794-32-8 N-<2-Carbethoxyethyl>-5-oxo-pyrrolidin-2-carbonsaeure-ethylester 
• 110523-58-5 phenyl N-(2-cyanoethyl)pyroglutamate 
• 110523-57-4 1-(2-Cyano-ethyl)-5-oxo-pyrrolidine-2-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

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.

HETEROCYCLIC 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 Gamma 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 Gamma activity, for example, autoimmune and/or inflammatory disorders.