193634-01-4

Upstream product

• 83649-48-3 (R)-3-amino-3-phenylpropionic acid hydrochloride 
• 93-11-8 2-Naphthalenesulfonyl chloride 
• 1190971-01-7 (3R)-(naphthalene-2-sulfonamido)-3-phenylpropionic acid tert-butyl ester 
• 161671-34-7 tert-butyl (R)-3-amino-3-phenylpropionate 
• 614-19-7 (R)-3-phenyl-3-aminopropionic acid 

Downstream Products

• 1174282-44-0 (R)-N-(3-oxo-1-phenyl-3-(2-(piperidin-1-ylmethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)naphthalene-2-sulfonamide 
• 1174282-45-1 (R)-N-(3-(3-chloro-2-(piperidin-1-ylmethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-3-oxo-1-phenylpropyl)naphthalene-2-sulfonamide 
• 1174284-05-9 (R)-N-(3-oxo-1-phenyl-3-(3-(piperidin-1-ylmethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)propyl)naphthalene-2-sulfonamide 
• 1190970-05-8 (R)-N-(3-oxo-1-phenyl-3-(2-(piperidin-1-ylmethyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)propyl)naphthalene-2-sulfonamide 
• 784202-87-5 N-(6-formyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(naphthalene-2-sulfonylamino)-3-phenyl-propionamide 
• 925456-57-1 (R)-N-((R)-5-formyl-2,3-dihydro-1H-inden-1-yl)-3-(naphthalene-2-sulfonamido)-3-phenylpropanamide 

Relevant academic research and scientific papers

Potent nonpeptide antagonists of the bradykinin B1 receptor: Structure-activity relationship studies with novel diaminochroman carboxamides

The bradykinin B1 receptor is induced following tissue injury and/or inflammation. Antagonists of this receptor have been studied as promising candidates for treatment of chronic pain. We have identified aryl sulfonamides containing a chiral chroman diamine moiety that are potent antagonists of the human B1 receptor. Our previously communicated lead, compound 2, served as a proof-of-concept molecule, but suffered from poor pharmacokinetic properties. With guidance from metabolic profiling, we performed structure-activity relationship studies and have identified potent analogs of 2. Variation of the sulfonamide moiety revealed a preference for 3- and 3,4-disubstituted aryl sulfonamides, while bulky secondary and tertiary amines were preferred at the benzylic amine position for potency at the B1 receptor. Modifying the β-amino acid core of the molecule lead to the discovery of highly potent compounds with improved in vitro pharmacokinetic properties. The most potent analog at the human receptor, compound 38, was also active in a rabbit B1 receptor cellular assay. Furthermore, compound 38 displayed in vivo activity in two rabbit models, a pharmacodynamic model with a blood pressure readout and an efficacy model of inflammatory pain.

Substituted Spiroamine Compounds

Substituted spiroamine compounds corresponding to the formula (I) In which m, n, o, p, Q, r, s, t, R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7, R8, R9, R10 and R11 have defined meanings; a process for the preparation of such compounds, pharmaceutical compositions containing such compounds and the use of substituted spiroamines for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin 1 receptor.

SUBSTITUTED SULFONAMIDE DERIVATIVES

The invention relates to substituted sulfonamide derivatives, processes for the preparation thereof, medicaments containing these compounds and the use of substituted sulfonamide derivatives for the preparation of medicaments.

Substituted Sulfonamide Compounds

Substituted sulfonamide compounds corresponding to the formula I wherein m, n, p, Q, R1, R2, R3, R4, X, Y and Z have the respective meanings defined herein, pharmaceutical compositions containing such compounds, a process for their preparation, and the use of such compounds for the treatment and/or inhibition of pain and other conditions mediated by bradykinin receptor 1 (B1R) and/or bradykinin receptor 2 (B2R).

Identification of a nonpeptidic and conformationally restricted bradykinin B1 receptor antagonist with anti-inflammatory activity

We report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4-17 nM). At 90 mg/kg s.c., 28 decreased plasma extravasation in two rodent models of inflammation. A novel met

BICYCLIC COMPOUNDS HAVING BRADYKININ RECEPTORS AFFINITY AND PHARMACEUTICAL COMPOSITIONS THEREOF

Selected compounds are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and