142380-46-9

Upstream product

• 129776-60-9 benzyl (2R)-2-(Carboxymethyl)-4-methylpentanoate 
• 108-91-8 cyclohexylamine 
• 142380-12-9 (R)-2-Cyclohexylcarbamoylmethyl-4-methyl-pentanoic acid benzyl ester 

Downstream Products

• 179169-29-0 2-[(R)-1-((R)-2-Cyclohexylcarbamoylmethyl-4-methyl-pentanoylamino)-2-(1-methyl-1H-indol-3-yl)-ethyl]-5-methyl-oxazole-4-carboxylic acid benzyl ester 
• 179169-34-7 2-[(R)-1-((R)-2-Cyclohexylcarbamoylmethyl-4-methyl-pentanoylamino)-2-(1-methyl-1H-indol-3-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

Azole endothelin antagonists. 3. Using Δ log P as a tool to improve absorption

The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter Δ log P. Comparison of urea 2 with a series of well-absorbed compounds using A log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between Δ log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NS groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.

Peptide compound and its preparation

Novel peptides of the formula (I") STR1 in which R1 is hydrogen or acyl, R2c is lower alkyl, R3c is optionally N-substituted indolylmethyl, R4 is hydrogen, lower alkyl, C6-10 ar(lower)alkyl, amino(lower)alkyl, protected amino (lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl or optionally substituted heterocyclic (lower)alkyl, R5 is carboxy, protected carboxy, carboxy(lower)alkyl or protected carboxy(lower)alkyl, R7 is hydrogen or lower alkyl, and A is --O--, --NH--, lower alkylamino or lower alkylene, or a pharmaceutically acceptable salt thereof are disclosed. Additionally, the preparation of such peptides is described. The peptides are used to treat endothelin mediated diseases such as hypertension.