603128-64-9

Upstream product

• 124-63-0 methanesulfonyl chloride 
• 155975-19-2 (1R,2R)-trans-2-(N-tert-butyloxycarbonyl)amino-1-cyclohexanol 
• 110716-78-4 (1R,2R)-trans-2-azidocyclohexanol 
• 115586-44-2 Butyric acid (1S,2S)-2-azido-cyclohexyl ester 
• 119479-49-1 (1S,2S)-trans-2-azidocyclohexanol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 286-20-4 cyclohexane-1,2-epoxide 
• 931-15-7 (1R,2R)-2-aminocyclohexanol 

Downstream Products

• 603128-65-0 (1S,2R)-2-(N-tert-butyloxycarbonylamino)-1-azidocyclohexane 
• 882409-34-9 (1S,2R)-cis-2-(N-tert-butyloxycarbonyl)amino-cyclohexyl-1-thioacetate 
• 875923-28-7 (3aRS,7aSR)-octahydro-2H-benzimidazol-2-one 
• 882409-38-3 (1R,2S)-2-Benzylsulfanyl-cyclohexylamine 
• 882409-36-1 ((1R,2S)-2-Mercapto-cyclohexyl)-carbamic acid tert-butyl ester 
• 882409-35-0 (1S,2R)-cis-1-(S-benzyl)sulfanyl-2-(N-tert-butyloxycarbonyl)amino-cyclohexane 
• 364385-54-6 (1S,2R)-2-tert-Butoxycarbonylamino-cyclohexylamine 
• 1427038-68-3 succinimidyl (1R,2S)-2-azidocyclohexylcarbamate 

Relevant academic research and scientific papers

ALK5 INHIBITORS

The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

Helix-forming propensity of aliphatic urea oligomers incorporating noncanonical residue substitution patterns

Aliphatic N,N′-linked oligoureas are peptidomimetic foldamers that adopt a well-defined helical secondary structure stabilized by a collection of remote three-center H-bonds closing 12- and 14-membered pseudorings. Delineating the rules that govern helix formation depending on the nature of constituent units is of practical utility if one aims to utilize this helical fold to place side chains in a given arrangement and elaborate functional helices. In this work, we tested whether the helix geometry is compatible with alternative substitution patterns. The central -NH-CH(R)-CH2-NH-CO- residue in a model oligourea pentamer sequence was replaced by guest units bearing various substitution patterns [e.g., -NH-CH2-CH2-NH-CO-, -NH-CH2-CH(R)-NH-CO-, and -NH-CH(R1)-CH(R 2)-NH-CO-], levels of preorganization (cyclic vs acyclic residues), and stereochemistries, and the helix formation was systematically assessed. The extent of helix perturbation or stabilization was primarily monitored in solution by Fourier transform IR, NMR, and electronic circular dichroism spectroscopies. Our results indicate that although three new substitution patterns were accommodated in the 2.5-helix, the helical urea backbone in short oligomers is particularly sensitive to variations in the residue substitution pattern (position and stereochemistry). For example, the trans-1,2- diaminocyclohexane unit was experimentally found to break the helix nucleation, but the corresponding cis unit did not. Theoretical calculations helped to rationalize these results. The conformational preferences in this series of oligoureas were also studied at high resolution by X-ray structure analyses of a representative set of modified oligomers.

Novel Compounds

Compounds of Formulae I, or pharmaceutically acceptable salts thereof: wherein A1, A2, G1, G2 G3, R1, R2, X, Y, Z, m, n and p are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

Resolution of racemic 2-aminocyclohexanol derivatives and their application as ligands in asymmetric catalysis

A preparatively easy and efficient protocol for the resolution of racemic 2-aminocyclohexanol derivatives is described, delivering both enantiomers with >99% enantiomeric excess (ee) by sequential use of (R)- and (S)-mandelic acid. A simple aqueous workup procedure permits the isolation of the amino alcohols in analytically pure form and the almost quantitative recovery of mandelic acid. Debenzylation of enantiopure trans-2-(N-benzyl)amino-1- cyclohexanol by hydrogenation and subsequent derivatization give access to a broad variety of diversely substituted derivatives. Furthermore, the corresponding cis isomers are readily available. Applications of these optically active aminocyclohexanols in catalyzed asymmetric phenyl transfer reactions to benzaldehydes and transfer hydrogenations of aryl ketones lead to products with up to 96% ee.

Synthesis and Evaluation of (1S,2R/1R,2S)-Aminocyclohexylglycyl PNAs As Conformationally Preorganized PNA Analogues for DNA/RNA Recognition

Conformationally constrained cis-aminocyclohexylglycyl PNAs have been designed on the basis of stereospecific imposition of 1,2-cis-cyclohexyl moieties on the aminoethyl segment of aminoethylglycyl PNA (aegPNA). The introduction of the cis-cyclohexyl ring

(1S,2R/1R,2S)-aminocyclohexyl glycyl thymine PNA: Synthesis, monomer crystal structures, and DNA/RNA hybridization studies

(Matrix Presented) The synthesis of ethyl cis-(1s,2R/1R,2S)-2.aminocyclohex-1-yI-N-(thymin-1-yl-acetyl) glycinate (10a and 10b) via enzymatic resolution of the key racemic intermediate trans-2-azido cyclohexanols 3 is reported. The crystal structures of 10 show equatorial disposition of the tertiary amide group, with the torsion angle β in the range 60-70°. The PNA oligomers incorporating these show differential effects in hybridizing with complementary DNA and RNA.