1252632-10-2

Upstream product

• 1252632-04-4 1-tert-butyl 2-methyl (2S,4R)-4-[(2-chlorophenyl)sulfanyl]pyrrolidine-1,2-dicarboxylate 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 84520-67-2 (2S,4R)-4-(methylsulfonyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butylester-2-methylester 
• 121147-93-1 (2S,4S)-2-methyl N-Boc-4-((methylsulfonyl)oxy)pyrrolidine-2-carboxylate 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 1252633-25-2 (2S,4S)-1-tert-butyl 2-methyl 4-(3-nitrophenylsulfonyloxy)pyrrolidine-1,2-dicarboxylate 

Downstream Products

• 1252637-53-8 (2S,4R)-methyl 4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylate 
• 1439404-48-4 (2S,4R)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylic acid 
• 1439404-47-3 (2S,4R)-methyl 1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylate 
• 1252632-39-5 (2S,4R)-4-(2-chlorobenzenesulfonyl)-2-(1-cyanocyclopropylcarbamoyl)pyrrolidine hydrochloric acid 
• 1252632-52-2 (2S,4R)-1-benzoyl-4-[(2-chlorobenzene)sulfonyl]-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 
• 1252632-77-1 (2S,4R)-4-[(2-chlorobenzene)sulfonyl]-N-(1-cyanocyclopropyl)-1-cyclohexanecarbonylpyrrolidine-2-carboxamide 
• 1252632-79-3 (2S,4R)-1-acetyl-4-[(2-chlorobenzene)sulfonyl]-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 
• 1252633-65-0 (2S,4R)-4-(2-chloro-4-fluorophenylsulfonyl)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 
• 1252632-24-8 tert-butyl (2S,4R)-4-[(2-chlorophenyl)sulfonyl]-2-{[(1-cyanocyclopropyl)amino]carbonyl}pyrrolidine-1-carboxylate 
• 1252632-16-8 (2S,4R)-1-(tert-butoxycarbonyl)-4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylic acid 

Relevant academic research and scientific papers

Synthesis of proline analogues as potent and selective cathepsin S inhibitors

Cathepsin S is a potential target of autoimmune disease. A series of proline derived compounds were synthesized and evaluated as cathepsin S inhibitors. We discovered potent cathepsin S inhibitors through structure-activity relationship studies of proline analogues. In particular, compound 19-(S) showed promising in vitro/vivo pharmacological activities and properties as a selective cathepsin S inhibitor.

NOVEL PYRROLIDINE DERIVATIVES

The invention relates to a compound of formula (I) wherein A and R1 to R7 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

NOVEL PYRROLIDINE DERIVATIVES AS INHIBITORS OF CATHEPSIN

The invention relates to a compound of formula (I), wherein A and R1 to R7 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

Identification of potent and selective cathepsin S inhibitors containing different central cyclic scaffolds

Starting from the weakly active dual CatS/K inhibitor 5, structure-based design supported by X-ray analysis led to the discovery of the potent and selective (>50 000-fold vs CatK) cyclopentane derivative 22 by exploiting specific ligand-receptor interactions in the S2 pocket of CatS. Changing the central cyclopentane scaffold to the analogous pyrrolidine derivative 57 decreased the enzyme as well as the cell-based activity significantly by 24- and 69-fold, respectively. The most promising scaffold identified was the readily accessible proline derivative (e.g., 79). This compound, with an appealing ligand efficiency (LE) of 0.47, included additional structural modifications binding in the S1 and S3 pockets of CatS, leading to favorable in vitro and in vivo properties. Compound 79 reduced IL-2 production in a transgenic DO10.11 mouse model of antigen presentation in a dose-dependent manner with an ED 50 of 5 mg/kg.

NOVEL PYRROLIDINE DERIVATIVES

The invention relates to a compound of formula (I) wherein A1 to A3 and R1 to R3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

NOVEL PYRROLIDINE DERIVATIVES

The invention relates to a compound of formula (I) wherein A1 to A3 and R1 to R3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.