132622-92-5

Usage

Structure

Ester derivative of 1,2-pyrrolidinedicarboxylic acid

Functional Groups

Hydroxy group
Tert-butyl group
Phenylmethyl group

Stereochemistry

2R,4R configuration

Potential Applications

Pharmaceutical industry
Chemical industry

Safety Precautions

Handle and use with caution due to complex structure and potential effects

Molecular Weight

315.4 g/mol

Appearance

Unknown, may vary depending on the form (e.g., solid, liquid)

Solubility

Unknown, may depend on the solvent used

Stability

Unknown, may be sensitive to heat, light, or moisture

Reactivity

Unknown, may react with strong acids, bases, or other reactive chemicals

Toxicity

Unknown, should be handled with care and proper safety measures

Environmental Impact

Unknown, potential effects on the environment should be considered

Storage

Should be stored in a cool, dry, and well-ventilated area, away from heat, light, and moisture

Disposal

Dispose of according to local regulations and guidelines for chemical waste

Synonyms

Unknown, may have alternative names or trade names

Melting Point

Unknown, may vary depending on the specific conditions

Boiling Point

Unknown, may vary depending on the specific conditions

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 132622-89-0 benzyl (4R)-4-hydroxy-D-prolinate 
• 2584-71-6 cis-hydroxy-D-proline 
• 100-39-0 benzyl bromide 
• 135042-12-5 (4R)-1-(tert-butoxycarbonyl)-4-hydroxy-D-proline 
• 77449-94-6 (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid hydrochloride 
• 1738-76-7 glycine benzyl ester p-toluenesulfonic acid salt 

Downstream Products

• 481704-22-7 (2R,4S)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 1018332-19-8 2-benzyl 1-tert-butyl (2R,4S)-4-azidopyrrolidine-1,2-dicarboxylate 
• 1018332-23-4 (4S)-1-(tert-butoxycarbonyl)-4-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-D-proline 
• 132622-78-7 (4S)-1-(tert-butoxycarbonyl)-4-amino-D-proline 
• 1610033-40-3 2-((2R,4R)-1-(4-((1-(2-fluoro-5-methoxyphenyl)pyrrolidin-3-yl)oxy)phenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)acetonitrile 
• 1610033-10-7 methyl 2-((2R,4R)-1-(4-((1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl)oxy)phenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)acetate 
• 1610033-09-4 methyl 2-((2R,4R)-1-(4-hydroxyphenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)acetate 
• 1610033-08-3 2-((2R,4R)-1-(4-hydroxyphenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)acetonitrile 
• 1610033-07-2 2-((2R,4R)-1-(4-(benzyloxy)phenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)acetonitrile 
• 1610033-06-1 ((2R,4R)-1-(4-(benzyloxy)phenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)methanol 

Relevant academic research and scientific papers

Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library

Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.

SUBSTITUTED OXOPYRIDINE DERIVATIVES

The invention relates to substituted oxopyridine derivatives and to processes for preparation thereof, and also to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.

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.

Amino 6-membered ring derivative and pharmaceutical applications thereof including the use for manufacturing dipeptidyl peptidase-4(IDPP-IV) inhibitor

The present invention relates to an amino 6-membered ring derivative and pharmaceutical applications thereof, which specifically relates to the amino 6-membered ring derivative represented by the general formula (I) or stereoisomers thereof, pharmaceutically acceptable salts thereof, a prodrug, a pharmaceutical composition comprising the derivative, and the pharmaceutical use for manufacturing dipeptidyl peptidase-4(IDPP-IV) inhibitor, wherein the definition of each substituent in the general formula (I) is the same as described in the specification.

A short diastereoselective synthesis of cis-(2S,4S) and cis-(2R,4R)-4-hydroxyprolines

A concise synthesis of (2R,4R)-4-hydroxyproline (1) and (2S,4S)-4-hydroxyproline (2) has been developed in enantiomerically pure form from commercially available starting materials with excellent diastereoselectivity. The tightly bound chelation controlled transition state formed during the 5-exo-tet ring closure reaction is assumed to be the origin of high diastereoselectivity.

PYRROLIDINE 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.

Discovery of subnanomolar arginine-glycine-aspartate-based αvβ3/αvβ5 integrin binders embedding 4-aminoproline residues

The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity αvβ3/αvβ 5 integrin binders [IC50h(αvβ 3) 0.03-5.12 nM; IC50h(αvβ 5) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the Nα- nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the αvβ3 receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin αvβ3 complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.

CYCLIC AMINE BASE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT

Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is formula (I) X is -0-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25)or -SR35; R41 is alkyl, cycloalkyl, -S02(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is-C(O)-N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer’s disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Chimeric amino acid analogues

A chimeric amino acid analogue is provided suitable for incorporating into peptides which compound is represented by Formula 1: STR1 where P1 is preferably an amine protecting agent, and P2 and P3 are preferably amine or guanidine protecting agents. X can be OH, halide, or preferably an activating group suitable for conjugating the compound of Formula 1 to a peptide by conventional means, and m and n are 0-1 and 0-2 respectively. Peptides containing the chimeric amino acid analog are provided and include a platelet-aggregation inhibitor represented by where Aaa1 is Gly or H, Cpdl is the compound of Formula 1 which has been deprotected and Aaa2 is a hydrophobic amino acid preferably Val.