177477-92-8

Upstream product

• 177477-91-7 1-(tert-Butyldiphenylsilyloxymethyl)-2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl) cinnamoylglycyl]amino]-benzene 
• 167837-45-8 3-amino-1-(tert-butyldiphenylsilyloxymethyl)-2,6-dichlorobenzene 
• 167837-44-7 tert-butyl(2,6-dichloro-3-nitrobenzyloxy)diphenylsilane 
• 167837-57-2 4-(methylaminocarbonyl)-benzaldehyde 
• 619-66-9 4-Carboxybenzaldehyde 
• 179627-11-3 4-(methylcarbamoyl)cinnamic acid 
• 55775-97-8 2,6-dichloro-3-nitrobenzoic acid 
• 50-30-6 2,6-dichlorobenzoic acid 
• 167837-47-0 N-(3-((tert-butyldiphenylsilyloxy)methyl)-2,4-dichlorophenyl)-2-(1,3-dioxoisoindolin-2-yl)-N-methylacetamide 
• 177477-90-6 3-(N-Glycyl-N-methylamino)-1-(tert-butyldiphenyl-silyloxymethyl)-2,6-dichlorobenzene 
• 167837-46-9 N-(3-((tert-butyldiphenylsilyloxy)methyl)-2,4-dichlorophenyl)-2-(1,3-dioxoisoindol-in-2-yl)-acetamide 

Downstream Products

• 177477-93-9 2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl)cinnamoylglycyl)amino]benzyl bromide 
• 209919-52-8 FR 165649 

Relevant academic research and scientific papers

Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?

Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.

Benzimidazole compounds as bradykinin antagonists

PCT No. PCT/JP95/01478 Sec. 371 Date Feb. 3, 1997 Sec. 102(e) Date Feb. 3, 1997 PCT Filed Jul. 25, 1995 PCT Pub. No. WO96/04251 PCT Pub. Date Feb. 15, 1996This invention relates to a heterocyclic compound of the formula: wherein a group of the formula: is a group of the formula: etc., X is O, S or N-R5, R1 is lower alkyl, etc., R5 is hydrogen, lower alkyl, etc., R2 is hydrogen, halogen, lower alkyl, etc., R3 is halogen, lower alkyl, etc., R4 is amino optionally having suitable substituent(s), and A is lower alkylene, and a salt thereof, to processes for preparation thereof, and to a pharmaceutical composition comprising the same for the prevention and/or the treatment of bradykinin or its analogues mediated diseases in human being or animals.

Quinoline derivatives as bradykinin agonists

PCT No. PCT/JP97/00233 Sec. 371 Date Aug. 3, 1998 Sec. 102(e) Date Aug. 3, 1998 PCT Filed Jan. 31, 1997 PCT Pub. No. WO97/28153 PCT Pub. Date Aug. 7, 1997This invention relates to a compound of formula (1) wherein R1 is halogen, etc., R2 is halogen, etc., R3 is amino substituted with substituent(s) selected from the group consisting of lower alkyl and acyl, etc., R4 is heterocyclic (lower)alkyl, R5 is lower alkyl, and A1 is lower alkylene, and pharmaceutically acceptable salts thereof, to processes for preparation thereof, to a pharmaceutical composition comprising the same, and to methods of using the same therapeutically in the prevention and/or the treatment of hypertension or the like.

Pyridopyrimidones, quinolines and fused N-heterocycles as bradykinin antagonists

This invention relates to a compound of the formula: STR1 wherein Z is a group of the formula: STR2 in which X1 is N or C--R1, X2 is N or C--R9, X3 is N or C--R2, R1 is lower alk

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a]pyridine moiety

Recently we reported on overcoming the species difference of our first orally active non-peptide bradykinin (BK) B2 receptor antagonists, incorporating an 8-[[3-(N-acylglycyl-N-methylamino)-2,6-dichlorobenzyl]oxy]- 3-halo-2-methylimidazo[1,2-α]