138971-65-0

Upstream product

• 776-74-9 Bromodiphenylmethane 
• 119273-60-8 2-amino-3,3-diphenylpropanoic acid hydrochloride 
• 119363-63-2 2-(N-tert-butoxycarbonylamino)-3,3-diphenylpropanoic acid 
• 143646-43-9 ethyl acetamido(diphenylmethyl)cyanoacetate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 143218-20-6 2-tert-Butoxycarbonylamino-3,3-diphenyl-propionic acid 2,5-dioxo-pyrrolidin-1-yl ester 
• 147-85-3 L-proline 
• 143060-31-5 N-(tert-butoxycarbonyl)-3,3-diphenyl-D-alanine 
• 1028256-60-1 (S)-1-((R)-2-tert-Butoxycarbonylamino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid methyl ester 

Downstream Products

• 143217-75-8 (S)-1-(2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid [1-(3-guanidino-propyl)-2,5-dioxo-5-piperidin-1-yl-pentyl]-amide; compound with trifluoro-acetic acid 
• 143218-00-2 C₄₉H₆₇N₇O₉S 
• 143218-23-9 C₄₄H₅₈N₆O₁₀S 
• 143218-21-7 (S)-1-(2-tert-Butoxycarbonylamino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester 
• 138971-72-9 (1-{[(S)-1-((R)-2-tert-Butoxycarbonylamino-3,3-diphenyl-propionyl)-pyrrolidine-2-carbonyl]-amino}-hexyl)-phosphonic acid 
• 214153-66-9 (S)-1-((R)-3,3-Diphenyl-2-phenylmethanesulfonylamino-propionyl)-pyrrolidine-2-carboxylic acid [3-(1-trityl-1H-imidazol-4-yl)-prop-2-ynyl]-amide 

Relevant academic research and scientific papers

Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position

A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K(i) 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral P1 was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at P1 was a key step in our search for a clinical candidate.

Synthesis and biological activity of ketomethylene pseudopeptide analogues as thrombin inhibitors

Ketomethylene pseudopeptide analogues Aa-Pro-Argψ(COCH2)Gly-pip, 1, where Aa are D- or L-amino acids (Dpa, β,β-diphenylalanine; αNal, α- naphthylalanine; βNal, β-naphthylalanine; Fgl, fluorenylglycine) with highly lipophilic side chains and ψ(COCH2) is a ketomethylene pseudopeptide bond, have been synthesized through a modified Dakin-West reaction under very mild conditions with a high yield using tripeptide 4 with a labile functional group directly on the side chain. Their enzymatic assay of thrombin inhibition has been carried out. The structure-activity relationship study indicated that a lipophilic side chain on the amino acid in the P3 position is very important for binding to the apolar site of thrombin. Compound 1a with D-Dpa at the P3 position has a K(i) of 0.2 μM and it doubles thrombin clotting time at only 3 times higher concentration. These values are about 7 times better than those of the corresponding D-Phe analogues. Furthermore, 1a shows poor inhibitory activity against plasmin, factor Xa, urokinase, and kallikrein. Preliminary in vivo testing (3-4-kg rabbit as the animal model) shows no observable side effect (change of blood pressure and accumulation of blood platelet in lungs) at a dose of 1 mg/kg.