191613-89-5

Upstream product

• 1123-00-8 2-cyclopentylacetic acid 
• 40217-17-2 (R)-4-(phenylmethyl)-2-oxazolidinone 
• 1122-99-2 2-cyclopentylacetyl chloride 
• 90719-32-7 4-benzyl-2-oxazolidinone 
• 3282-30-2 pivaloyl chloride 

Downstream Products

• 191613-90-8 tert-butyl (R)-4-((R)-4-benzyl-2-oxooxazolidin-3-yl)-3-cyclopentyl-4-oxobutanoate 
• 191613-91-9 (R)-2-Cyclopentyl-succinic acid 1-benzyl ester 4-tert-butyl ester 
• 191613-93-1 (R)-2-Cyclopentyl-succinic acid 1-benzyl ester 4-(2-methyl-allyl) ester 
• 191613-92-0 (R)-2-Cyclopentyl-succinic acid 1-benzyl ester 

Relevant academic research and scientific papers

PROTEASOME INHIBITORS

The disclosure provides proteasome inhibitors that can be used to halt cell division of rapidly dividing cells by preventing the degradation of cell cycle-regulating proteins, such as cyclins, cyclin-dependent kinase inhibitors, and p53. The proteasome in

Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors

The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P1), peptidic core, (Px and Py), and end-cap (Pz) of our scaffold. The cystargolide derivative 5k, structurally unique at both Py and P1, exhibited the most promising inhibitory activity for the β5 subunit of human proteasomes (IC50 = 3.1 nM) and significant cytotoxicity towards MCF-7 (IC50 = 416 nM), MDA-MB-231 (IC50 = 74 nM) and RPMI 8226 (IC50 = 41 nM) cancer cell lines. Cellular infiltration assays revealed that minor structural modifications have significant effects on the ability of our PIs to inhibit intracellular proteasomes, and we identified 5k as a promising candidate for continued therapeutic studies. Our novel drug lead 5k is a more potent proteasome inhibitor than carfilzomib with mid-to-low nanomolar IC50 measurements and it is cytotoxic against multiple cancer cell lines at levels approaching those of carfilzomib.

BETA-TETRAZOLYL-PROPIONIC ACIDS AS METALLO-BETA-LACTAMASE INHIBITORS

The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

Metalloproteinase inhibitors

The present invention relates to therapeutically active hydroxamic acid, N-formyl-N-hydroxyamino and carboxylic acid derivatives, their preparation, and pharmaceutical compositions containing them. These compounds are useful in the inhibition of metallopr

Metalloproteinase inhibitors

PCT No. PCT/GB96/02877 Sec. 371 Date May 22, 1998 Sec. 102(e) Date May 22, 1998 PCT Filed Nov. 21, 1996 PCT Pub. No. WO97/19053 PCT Pub. Date May 29, 1997Compounds of general formula (I) wherein X ia a -CO2H, -NH(OH)CHO or -CONHOH group; R1 is a cylcoalkyl, cycloalkenyl or non-aromatic heterocyclic ring containing up to 3 heteroatoms, any of which may be (i) substituted by one ore more substituents selected from C1-C6 alkyl, C2-C6 alkenyl, halo, cyano (-CN), -CO2H, -CO2R, -CONH2, -CONHR, -CON(R)2, -OH, -OR, oxo-, -SH, -SR, -NHCOR, and -NHCO2R wherein R is C1-C6 alkyl or benzyl and/or (ii) fused to a cycloalky or heterocyclic ring; and R2, R3, R4 and R5 are as defined in specification are matrix metalloproteinase inhibitors.

The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an α-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNFα release.