158567-91-0

Usage

Chemical Properties

White powder

InChI:InChI=1/C16H21NO4/c1-16(2,3)21-15(20)17-10-12(9-13(17)14(18)19)11-7-5-4-6-8-11/h4-8,12-13H,9-10H2,1-3H3,(H,18,19)/t12-,13+/m0/s1

Upstream product

• 103290-38-6 C₁₇H₂₂NO₇S^(1-)*Li⁽¹⁺⁾ 
• 24424-99-5 di-tert-butyl dicarbonate 
• 96314-28-2 (2S,4R)-1-(tert-butoxycarbonyl)-4-(tosyloxy)pyrrolidine-2-carboxylic acid 
• 591-51-5 phenyllithium 
• 84348-37-8 N-tert-butoxycarbonyl-4-oxo-L-proline 
• 100-58-3 phenylmagnesium bromide 
• 98-80-6 phenylboronic acid 
• 462125-00-4 (S)-4-trifluoromethanesulfonyloxy-2,5-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 284047-10-5 1-tert-butyl 2-methyl (2S)-4-(trifluoromethanesulfonyloxy)-2,3-dihydropyrrole-1,2-dicarboxylate 
• 174905-43-2 4-phenyl-2,3-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 102195-80-2 (S)-1-tert-butyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 336818-16-7 (2S,4R)-4-Phenyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 35418-16-7 L-t-butyl pyroglutamate 

Downstream Products

• 1201986-89-1 2-nitro-N-(1-(5-((2S,4R)-4-phenyl-2-(((R)-3-phenyprrolidin-1-yl)methyl)pyrrolidine-1-carbonyl)furan-2-yl)ethyl)benzenesulfonamide 
• 1201986-87-9 methyl-(1-{5-[(2S,4R)-4-phenyl-2-((R)-3-phenyl-pyrrolidine-1-carbonyl)-pyrrolidine-1-carbonyl]-furan-2-yl}-ethyl)-carbamic acid tert-butyl ester 
• 1201986-54-0 ((R)-3-phenylpyrrolidin-1-yl)((2S,4R)-4-phenylpyrrolidin-2-yl)methanone hydrochloride 
• 1201986-61-9 4-benzyl-2-((2S,4R)-4-phenylpyrrolidin-2-yl)oxazole hydrochloride 
• 1201986-59-5 (2S,4R)-2-((naphthalen-1-yloxy)methyl)-4-phenylpyrrolidine hydrochloride 
• 1201986-92-6 [5-(1-methylamino-ethyl)-furan-2-yl]-[(2S,4R)-4-phenyl-2-((R)-3-phenyl-pyrrolidine-1-carbonyl)-pyrrolidin-1-yl]-methanone 
• 1201986-93-7 (5-(1-aminoethyl)furan-2-yl)((2S,4R)-4-phenyl-2-(((R)-3-phenylpyrrolidin-1-yl)methyl)pyrrolidin-1-yl)methanone 
• 1201986-77-7 (2S,4R)-tert-butyl-4-phenyl-2-((R)-3-phenylpyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate 
• 1201986-84-6 (2S,4R)-tert-butyl 2-((1-hydroxy-3-phenylpropan-2-yl)carbamoyl)-4-phenylpyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

Disulfide-Bridged Peptides That Mediate Enantioselective Cycloadditions through Thiyl Radical Catalysis

An enantioselective vinylcyclopropane ring-opening/cycloaddition cascade is described. The active thiyl radical catalysts are generated in situ via UV light-promoted homolysis of cystine-based dimers. Amide-functionalization of the peptide at the 4-proline position is essential for effective asymmetric induction. Stereochemical communication is dependent on steric interactions with this substituent that are enforced by H-bonding to the peptide backbone.

PYRROLIDINE GPR40 MODULATORS

The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate 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.

MODULATION OF TISSUE TRANSGLUTAMINASE ACTIVATION IN DISEASE

Compositions and methods are provided for modulating the physiological activation of tissue transglutaminase (TG2); which methods can include inhibiting the activity of TG2 associated with inflammatory disorders, which disorders may include, without limit

Discovery of potent and specific dihydroisoxazole inhibitors of human transglutaminase 2

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes the posttranslational modification of glutamine residues on protein or peptide substrates. A growing body of literature has implicated aberrantly regulated activity of TG2 in the pathogenesis of various human inflammatory, fibrotic, and other diseases. Taken together with the fact that TG2 knockout mice are developmentally and reproductively normal, there is growing interest in the potential use of TG2 inhibitors in the treatment of these conditions. Targeted-covalent inhibitors based on the weakly electrophilic 3-bromo-4,5-dihydroisoxazole (DHI) scaffold have been widely used to study TG2 biology and are well tolerated in vivo, but these compounds have only modest potency, and their selectivity toward other transglutaminase homologues is largely unknown. In the present work, we first profiled the selectivity of existing inhibitors against the most pertinent TG isoforms (TG1, TG3, and FXIIIa). Significant cross-reactivity of these small molecules with TG1 was observed. Structure-activity and -selectivity analyses led to the identification of modifications that improved potency and isoform selectivity. Preliminary pharmacokinetic analysis of the most promising analogues was also undertaken. Our new data provides a clear basis for the rational selection of dihydroisoxazole inhibitors as tools for in vivo biological investigation.

Discovery of a novel class of potent and orally bioavailable sphingosine 1-phosphate receptor 1 antagonists

A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P 1) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.

SPHINGOSINE-1-PHOSPHATE RECEPTOR ANTAGONISTS

This disclosure relates to sphingosine-1 -phosphate (SlP) receptor antagonists, compositions comprising the SlP receptor antagonists and methods for using and processes for making the SlP receptor antagonists. In particularly, this disclosure relates to sphingosine-1 -phosphate 1 (SlPl) receptor antagonists, compositions comprising the SlPl receptor antagonist and methods for using the SlPl receptor antagonist, such as in the treatment of cancer, and processes for making the SlPl receptor antagonists.

Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV

A series of (4-substituted prolyl)prolinenitriles were synthesized and evaluated as inhibitors of dipeptidylpeptidase IV (DPP-IV). Among those tested, the 4β-[4-(hydroxyphenyl)prolyl]prolinenitriles showed a potent inhibitory activity with a long duration

Synthesis and evaluation of some hydroxyproline-derived peptidomimetics as isoprenyltransferase inhibitors

CA1A2X peptidomimetics containing a modified proline at position A2 were prepared and evaluated for their ability to inhibit farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) in enzymatic and cell- bas

LITHIUM DIPHENYLCUPRATE REACTIONS WITH 4-TOSYLOXY-L-PROLINES; AN INTERESTING STEREOCHEMICAL OUTCOME. A SYNTHESIS OF TRANS-4-PHENYL-L-PROLINE.

The reaction of lithium diphenylcuprate with trans-4- and cis-4-tosyloxy-L-prolines gives excellent yields of 4-phenyl substituted L-prolines and the reaction proceeds with net retention of configuration at the carbon center bearing the tosyloxy group.

Method for making substituted prolines

A method is provided for making substituted prolines of the structure STR1 wherein X is lower alkyl or aryl, R is H, lower alkyl or an alkali metal and Z is an N-protecting group, which method includes the step of reacting a compound of the structure STR2