775223-82-0

Upstream product

• 186581-53-3 diazomethane 
• 681128-94-9 (2S)-5-methylpyrrolidine-2-carboxylic acid 
• 114486-35-0 Methyl 2-aminohex-5-enoate 
• 83483-17-4 methyl 2-nitro-5-oxohexanoate 
• 861657-91-2 rac-1-(tert-butyl) 2-methyl 5-oxopyrrolidine-1,2-dicarboxylate 
• 149-87-1 Pyroglutamic acid 
• 4931-66-2 methyl 5-oxopyrrolidine-2-carboxylate 
• 137131-35-2 5-methoxy-3,4-dihydro-2H-pyrrole-2-carboxylic acid methyl ester 
• 150133-57-6 isopropylidene-(2-methoxycarbonyl-5-pyrrolidinylidene)malonate 
• 107938-26-1 benzyl (5-methoxycarbonyl-2-pyrrolidinylidene)acetate 
• 108963-96-8 (S)-1-tert-butoxycarbonyl-5-methoxycarbonyl-pyrrolidin-2-one 

Relevant academic research and scientific papers

Design and Synthesis of 56 Shape-Diverse 3D Fragments

Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol?1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity.

2-PYRROLIDINE PHENYLHYDRAZIDES ANTIBACTERIAL AGENTS

2-Pyrrolidine phenylhydrazides antibacterial agents The present invention relates to 2-pyrrolidine phenylhydrazide compounds of formula (I), which are selective antibacterials specifically agalnstAcineto barter baumannii.The invention also relates to their therapeutic use as antibacterials, to a process for their preparation and to pharmaceutical compositions containing them.

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.

NOVEL HEPATITIS C VIRUS INHIBITORS

The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

cis-2,5-dicyanopyrrolidine inhibitors of dipeptidyl peptidase IV: Synthesis and in vitro, in vivo, and x-ray crystallographic characterization

Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine α-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl)cyclopentyl]amino}-acetyl)pyrrolidine-2,5-cis- dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

Cyclisation of aminyl radicals derived from amino acids

α-Amino acid aminyl radicals have been generated from sulfenamide precursors using Bu3SnH. The aminyl radicals undergo 5-exo-trig cyclisation reactions onto suitably placed N-alkenyl or α-alkenyl chains on the amino acids with reasonable diastereoselectivity. The α-ester of the amino acid imparts electrophilic behaviour to the aminyl radicals and facilitates cyclisation onto alkenes.

SYNTHESIS OF 3,5-TRANS-3-METHOXYCARBONYL-1-CARBAPENAM FROM METHYL (+/-)-PYROGLUTAMATE

Synthesis of 3,5-trans-3-methoxycarbonyl-1-carbapenam in six steps from methyl (+/-)-pyroglutamate is described.

COPPER(II) IN ORGANIC SYNTHESIS. II. A STEREOCONTROLLED ROUTE TO ALKYLPROLINES

The copper(II)-catalyzed Michael reaction between nitroacetic esters and α,β-unsaturated ketones gives good yields of 2-nitro-5-keto esters.Their reductive cyclization with H2 and C/Pd in the presence of anhydrous Na2SO4 offers a useful route to proline derivatives whose configuration was assigned by 1H- and 13C-NMR.