919352-63-9

Upstream product

• 7517-19-3 methyl (L)-leucinate hydrochloride 
• 61-90-5 L-leucine 
• 16184-89-7 4'-bromo-2,2,2-trifluoroacetophenone 
• 867011-60-7 (2S)-2-[1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol 
• 603142-80-9 (2S)-2-[(1S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentan-1-ol 
• 603142-79-6 [(S)-1-(tert-butyl-dimethyl-silanyloxymethyl)-3-methyl-butyl]-[2,2,2-trifluoro-eth-(E)-ylidene]-amine 
• 106163-44-4 (S)-1-((tert-butyldimethylsilyl)oxy)-4-methylpentan-2-amine 
• 7533-40-6 (S)-2-amino-4-methylpentan-1-ol 

Downstream Products

• 919351-59-0 (S)-2-[(S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethylamino]-1-((3R,3aR,6S,6aS)-6-fluoro-3-hydroxy-hexahydro-furo[3,2-b]pyrrol-4-yl)-4-methyl-pentan-1-one 
• 919352-25-3 (S)-2-[(S)-1-(4-Bromo-phenyl)-2,2,2-trifluoro-ethylamino]-4-methyl-pentanoic acid isopropyl ester 
• 603142-84-3 N¹-(cyanomethyl)-N²{(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-L-leucinamide 

Relevant academic research and scientific papers

Synthesis and structure-activity relationship of nitrile-based cruzain inhibitors incorporating a trifluoroethylamine-based P2 amide replacement

The structure-activity relationship for nitrile-based cruzain inhibitors incorporating a P2 amide replacement based on trifluoroethylamine was explored by deconstruction of a published series of inhibitors. It was demonstrated that the P3 biphenyl substituent present in the published inhibitor structures could be truncated to phenyl with only a small loss of affinity. The effects of inverting the configuration of the P2 amide replacement and linking a benzyl substituent at P1 were observed to be strongly nonadditive. We show that plotting affinity against molecular size provides a means to visualize both the molecular size efficiency of structural transformations and the nonadditivity in the structure-activity relationship. We also show how the relationship between affinity and lipophilicity, measured by high-performance liquid chromatography with an immobilized artificial membrane stationary phase, may be used to normalize affinity with respect to lipophilicity.

Cathepsin K inhibitors and application thereof

The invention provides cathepsin K inhibitors and application thereof. The invention relates to compounds used for treating or preventing cathepsin-dependent diseases and pharmaceutical compositions thereof. The compounds and the pharmaceutical compositions containing the compounds can be used as bone resorption inhibitors for treatment of related diseases. Cathepsins in the invention include, but not limited to, cathepsin K.

Cathepsin K inhibitors and use thereof

The invention relates to compounds and pharmaceutical compositions thereof for treatment or prevention of cathepsin dependent diseases; the compounds and the compositions comprising the compounds can be used as bone absorption inhibitors for treatment of related diseases, wherein the cathepsin includes, but is not limited to, cathepsin K.

Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease

Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 por

Diastereoselective reductive amination of aryl trifluoromethyl ketones and α-amino esters

(Chemical Equation Presented) Reductionist art: Careful choice of the reducing agent in the reductive amination of trifluoromethyl ketones with α-amino esters allows stereoselective access, from the imine formed, to either the R,S or S,S diastereomers of the resulting amino acids. Whereas NaBH4 affords the R,S diastereomers, Zn(BH4)2 affords the S,S diastereomers (see scheme), which can be easily converted into potent cathepsin K inhibitors.

CYSTEINE PROTEASE INHIBITORS

A compound of the formula (II) wherein one of R1 and R2 is halo and the other is H or halo; R3 is -C1-C5 straight or branched chain, optionally fluorinated, alkyl or -CH2CR5Csub

Identification of a potent and selective non-basic cathepsin K inhibitor

Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of cathepsin K inhibitor, further optimization led to identification of compound 22 (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This compound showed e

Cathepsin cysteine protease inhibitors

This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.