842136-44-1

Upstream product

• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 622-95-7 4-chlorobenzyl bromide 
• 959130-62-2 (2S,4R)-4-(4-Chloro-benzyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 67-56-1 methanol 

Downstream Products

• 1000991-78-5 C₁₃H₁₆ClNO₃ 
• 842136-07-6 (2S,4R)-4-(4-Chloro-benzyloxy)-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 842136-09-8 (2S,4R)-2-azidomethyl-4-(4-chlorobenzyloxy)pyrrolidine-1-carboxylic acid tert-butyl ester 
• 842136-11-2 (2S,4R)-2-Aminomethyl-4-(4-chloro-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 842136-06-5 (2S,4R)-4-(4-chlorobenzyloxy)-2-hydroxymethylpyrrolidine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS

The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTlVATING PROTEASE INHIBITORS

The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design

Structure-based design was utilized to guide the early stage optimization of a substrate-like inhibitor to afford potent peptidomimetic inhibitors of the channel-activating protease prostasin. The first X-ray crystal structures of prostasin with small molecule inhibitors bound to the active site are also reported.

Compounds and Compositions as Channel Activating Protease Inhibitors

The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

Compounds and Compositions as Channel Activating Protease Inhibitors

The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B

Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of PKB as potential antitumour agents was investigated. Constrained pyrrolidine analogues that mimicked the bound conformation of linear prototypes were identified and investigated by co-crystal structure determinations with the related protein PKA. Detailed variation in the binding modes between inhibitors with similar overall conformations was observed. Potent PKB inhibitors from this series inhibited GSK3β phosphorylation in cellular assays, consistent with inhibition of PKB kinase activity in cells.

PHARMACEUTICAL COMPOUNDS

The invention provides compounds for the prophylaxis or treatment of a disease state or condition mediated by protein kinase A or protein kinase B, the compounds having the formula (I°), or being salts or solvates thereof. In formula (I°), n is 0 or 1; A and E are alkylene 2-3 carbon atoms in length optionally substituted by R11 and -X-CH(R6)(R7); G is hydrogen when n is 0 and, when n is 1, G is hydrogen or -X-CH(R6)(R7); R1 is an aryl or heteroaryl group having 5-12 ring members; R2 and R4 are selected from hydrogen, R7,R11 and CH(R6)(R7); R3, R3a and R5 are selected from hydrogen, R11 and -X-CH(R6)(R7); or any one pair or any two non-overlapping pairs selected from R2 and R3; R3 and R4; R2 and R5; R3 and R5; R4 and R5; R3 and R8; and R4 and R8 are linked together in a ring and together form an alkylene chain of 1-5 carbon atoms in length which may be optionally substituted by R11 and -X-CH(R6)(R7); or the pair R2 and R4 are linked together in a ring and together form an alkylene chain of 2-5 carbon atoms in length which may be optionally substituted by R11 and -X-CH(R6)(R7); and optionally R3 and R3a may be linked together in a ring and together form an alkylene chain of 1-6 carbon atoms in length which may be optionally substituted by R11 and -X-CH(R6)(R7); or R6 and R7 together with the carbon atom to which they are attached form a cyclic group having 5-12 ring members; X, R6, R7, R8, R9, R10 and R11 are each as defined in claim 1; and wherein the definitions of, A, E, G, X, n and R1 to R11 are subject to the provisos set ou in claim 1.