877995-77-2

Upstream product

• 106-41-2 4-bromo-phenol 
• 1026786-57-1 1,3-dichloro-2-(2-chloro-ethoxy)-5-methyl-benzene 
• 2432-12-4 2,6-dichloro-4-methylophenol 
• 55162-34-0 1-bromo-4-(2-chloroethoxy)benzene 
• 34743-88-9 2-(4-bromophenoxy)ethanol 
• 945999-94-0 2-(4-bromophenoxy)ethyl methanesulfonate 

Downstream Products

• 1041439-27-3 C₅₂H₅₇Cl₂N₃O₈ 
• 946002-30-8 4-{4-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester 3-methyl Ester 
• 1149625-72-8 (1R,5S)-7-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-9-methyl-3,9-diazabicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester 
• 921630-61-7 4-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-benzaldehyde 
• 930798-42-8 (3R,4S)-1-benzyl-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}pyrrolidine-3-carboxylic acid 
• 930798-41-7 (3R,4S)-1-benzyl-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}pyrrolidine-3-carboxylic acid tert-butyl ester 
• 930798-43-9 (3R,4S)-1-benzyl-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}pyrrolidine-3-carboxylic acid cyclopropyl-(2,3-dimethylbenzyl)amide 
• 946003-61-8 (3R,4S)-3-{[5-Chloro-2-(3-methoxy-propyl)-pyridin-4-ylmethyl]-cyclopropyl-carbamoyl}-4-{4-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-phenyl}-piperidine-1-carboxylic Acid tert-butyl Ester 

Relevant academic research and scientific papers

Practical synthesis of a renin inhibitor via a diastereoselective dieckmann cyclization

A scalable synthesis of a potent renin inhibitor (1) is described. The absolute stereochemistry is set via an unprecedented diastereoselective Dieckmann cyclization directed by a remote chiral protecting group. This transformation enables preparation of chiral 1,3-[3.3.1]-diazabicyclononenes by desymmetrization of alkyl-esters, with selectivities ranging from 4 to 17:1.

Secondary Amines as Renin Inhibitors

The invention relates to novel secondary amine derivatives of formula (I) and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors

Starting from known piperidine renin inhibitors, a new series of 3,9-diazabicyclo[3.3.1]nonene derivatives was rationally designed and prepared. Optimization of the positions 3, 6, and 7 of the diazabicyclonene template led to potent renin inhibitors. The substituents attached at the positions 6 and 7 were essential for the binding affinity of these compounds for renin. The introduction of a substituent attached at the position 3 did not modify the binding affinity but allowed the modulation of the ADME properties. Our efforts led to the discovery of compound (+)-26g that inhibits renin with an IC 50 of 0.20 nM in buffer and 19 nM in plasma. The pharmacokinetics properties of this and other similar compounds are discussed. Compound (+)-26g is well absorbed in rats and efficacious at 10 mg/kg in vivo.

A PROCESS FOR PREPARING DIAZABICYCLO[3.3.1] NONANE COMPOUNDS

The invention is a process for preparing a diazabicyclo compound of formula (I) process for preparing a diazabicyclo compound of formula (I):where X is selected from the group consisting of hydrogen, C1-C6 alkoxycarbonyl, and carbobenzyloxy; R6 is selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and benzyl; and R9, R 10, and R11 are independently selected from the group consisting of hydrogen, halogen, and C1-C6 alkyl. wherein the process involves cyclizing I-I, formula (II).

NOVEL CASE OF RENIN INHIBITORS

The present invention relates to piperidine-based renin inhibitor compounds having carboxylate or carboxylic acid terminal groups. The disclosed low molecular weight, orally active renin inhibitors are of non-peptide nature and have long duration of action. The compounds can be used in the treatment of cardiovascular events and renal insufficiency.

RENIN INHIBITORS

The present invention relates to disubstituted piperidinyl renin inhibitor compounds having the structure (Formula I) and their use in treating cardiovascular events and renal insufficiency.

SECONDARY AMINES AS RENIN INHIBITORS

The invention relates to novel secondary amine derivatives of formula (I) and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

PYRROLIDINE-3-CARBOXYLIC ACID AMIDE DERIVATIVES AND THEIR USE AS INHIBITORS OF RENIN

The invention relates to novel pyrrolidine-3-carboxylic acid amide derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of these novel compounds, pharmaceutical compositions comprising such compounds and especially the use of such compounds as inhibitors of renin.

7- {4- [2- (2 , 6-DICHL0R0-4-METHYLPHEN0XY) ETHOXY] PHENYL}-3 , 9-DIAZABICYCLO [3 .3 . 31] NON - 6-ENE- S- CARBOXYLIC ACID CYCLOPROPYL- (2 , 3-DIMETHYLBENZYD AMIDE AS INHIBITORS OF RENIN FOR THE TREATMENT OF HYPERTENSION

The invention relates to a novel 3,9-diazabicyclα [3.3. ljnonene derivative of formula (I) and the enantiomers thereof and the use thereof as active ingredients in the preparation of pharmaceutical compositions . The invention also concerns related aspects including pharmaceutical compositions containing at least one compound of formula (I) or (I') and especially their use as inhibitors of renin.(I).