192516-54-4

Upstream product

• 225377-22-0 1,1-dimethylethyl N-(cyclohexyl)-N-<2-amino>-2-oxoethyl>carbamate 
• 144006-28-0 ethyl 2-<(cyclohexylmethyl)amino>acetate 
• 3218-02-8 cyclohexylmethylamine 
• 143935-49-3 1,1-dimethylethyl N-(carboxymethyl)-N-(cyclohexylmethyl)carbamate 
• 225377-11-7 1,1-dimethylethyl N-(cyclohexylmethyl)-N-(2-ethoxy-2-oxoethyl)carbamate 
• 5638-76-6 betahistine 

Downstream Products

• 225378-74-5 3-<4-<(cyclohexylmethyl)-<2-amino>-2-oxoethyl>amino>-1,4-dioxo-2(R)-<<2-<<(2,2,2-trichloroethoxy)carbonyl>amino>-4-thiazolyl>methyl>butyl>-4(S)-(1-methylethyl)-2-oxazolidinone 
• 245756-15-4 2-(2-chloro-allyl)-N⁴-cyclohexylmethyl-N¹-(1-cyclohexylmethyl-5-methyl-hex-2-enyl)-N⁴-{[methyl-(2-pyridin-2-yl-ethyl)-carbamoyl]-methyl}-succinamide 
• 192516-55-5 4-chloro-2-[(cyclohexylmethyl-{[methyl-(2-pyridin-2-yl-ethyl)-carbamoyl]-methyl}-carbamoyl)-methyl]-pent-4-enoic acid methyl ester 
• 245756-11-0 2-(2-chloro-allyl)-N⁴-cyclohexylmethyl-N¹-(1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexyl)-N⁴-{[methyl-(2-pyridin-2-yl-ethyl)-carbamoyl]-methyl}-succinamide 
• 294856-57-8 3-[4-bromo-2(S)-[2-[(cyclohexylmethyl)[2-[methyl[2-(2-pyridinyl)ethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]-1-oxo-4-pentenyl]-4(S)-(1-methylethyl)-2-oxazolidinone 
• 160937-56-4 BILA 2157 BS 
• 294856-58-9 2(S)-(2-bromo-2-propenyl)-4-[(cyclohexylmethyl)[2-[methyl[2-(2-pyridinyl)ethyl]amino]-2-oxo-ethyl]amino]-4-oxobutanoic acid 
• 294856-61-4 N⁴-(cyclohexylmethyl)-N⁴-[2-[methyl[2-(2-pyridinyl)ethyl]amino]-2-oxoethyl]-N¹-[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]-2(S)-(2-bromo-2-propenyl)butanediamide 
• 294856-63-6 2-(2-bromo-allyl)-N¹-[2-cyclohexyl-1-(5-isobutyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-N⁴-cyclohexylmethyl-N⁴-{[methyl-(2-pyridin-2-yl-ethyl)-carbamoyl]-methyl}-succinamide 
• 245756-18-7 2-(2-chloro-allyl)-N¹-[2-cyclohexyl-1-(5-isobutyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-N⁴-cyclohexylmethyl-N⁴-{[methyl-(2-pyridin-2-yl-ethyl)-carbamoyl]-methyl}-succinamide 
• 225378-79-0 N⁴-(cyclohexylmethyl)-N¹-<1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl>-N⁴-<2-amino>-2-oxoethyl>-2(R)-<<2-<<(2,2,2-trichloroethoxy)carbonyl>amino>-4-thiazolyl>methyl>butanediamide 

Relevant academic research and scientific papers

Stereoselective synthesis of renin inhibitor BILA 2157 BS

We have developed a convergent and stereoselective synthesis of orally active renin inhibitor BILA 2157 BS. Three building blocks were used to generate the basic skeleton of the inhibitor. The key feature consisted of the late elaboration of the 2-amino-4-thiazolyl heterocycle from a vinylbromide precursor. The synthetic sequence, which required a total of 22 chemical steps, provided 0.6 kg of BILA 2157 BS in 7.3% overall yield.

Practical Synthesis of BILA 2157 BS, a Potent and Orally Active Renin Inhibitor: Use of an Enzyme-Catalyzed Hydrolysis for the Preparation of Homochiral Succinic Acid Derivatives

We have developed a highly convergent and stereoselective synthesis of BILA 2157 BS, a potent and orally active renin inhibitor. The synthesis proceeds in 15 distinct chemical steps (with several integrated, multistep operations) from aminodiol 4. The key step in the synthesis involves the use of an enantiospecific, enzyme-catalyzed hydrolysis of a substituted succinate diester to provide a homochiral succinic acid derivative in 98% enantiomeric excess (≥2.5 kg scale). Recycling of the unwanted enantiomer is accomplished through base-catalyzed racemization, leading to an efficient deracemization of the starting racemic diester. The entire sequence proceeds without chromatographic purifications and delivers the product with >97% homogeneity. In addition, compared to the previously reported syntheses of BILA 2157 BS, this approach avoids the use of expensive chiral auxiliaries and cryogenics and, thus, should be amenable to the preparation of large quantities of this peptidomimetic inhibitor.

Discovery of non-peptidic P2-P3 butanediamide renin inhibitors with high oral efficacy

A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P2 and P3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4nM and 2.5 to 7.6nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. Copyright (C) 1999 Elsevier Science Ltd.