157245-84-6

Upstream product

• 2969-81-5 Ethyl 4-bromobutyrate 
• 591-20-8 3-Bromophenol 

Downstream Products

• 1307813-30-4 3-(5-phenyl-4-(trifluoromethyl)isoxazole-3-yl)-2,3-dihydrobenzo[b]oxepino-[4,5-d]isoxazole-8-carbaldehyde 
• 1307813-29-1 3-(5-phenyl-4-(trifluoromethyl)isoxazole-3-yl)-8-vinyl-2,3-dihydrobenzo[b]oxepino-[4,5-d]isoxazole 
• 1307813-28-0 3-(5-phenyl-4-(trifluoromethyl)isoxazole-3-yl)-8-bromo-2,3-dihydrobenzo[b]oxepino-[4,5-d]isoxazole 
• 1307810-20-3 1-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydrobenzo[6,7]oxepino[4,5-d]isoxazol-8-yl)methyl)-azetidine-3-carboxylic acid 
• 1282529-47-8 [5-(8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-carbamic acid benzyl ester 
• 141106-23-2 8-bromo-3,4-dihydrobenzo[b]oxepin-5(2H)-one 
• 170638-88-7 4-(3-bromophenoxy)butanoic acid 
• 1443670-50-5 5-(3-bromophenoxy)-2-methylpentan-2-ol 
• 1282529-99-0 8-bromo-N-(2-chloro-5-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide 
• 1282529-98-9 3-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoic acid 
• 1282529-97-8 methyl 3-(8-bromo-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoate 
• 1282529-96-7 methyl 3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoate 
• 1189811-67-3 8-(3-(aminomethyl)phenyl)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide 
• 1189816-09-8 8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide 

Relevant academic research and scientific papers

Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6- dihydrobenzo[f]imidazo[1,2- d ][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2- methylpropanamide (GDC-0032): A β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity

Dysfunctional signaling through the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway leads to uncontrolled tumor proliferation. In the course of the discovery of novel benzoxepin PI3K inhibitors, we observed a strong dependency of in vivo antitumor activity on the free-drug exposure. By lowering the intrinsic clearance, we derived a set of imidazobenzoxazepin compounds that showed improved unbound drug exposure and effectively suppressed growth of tumors in a mouse xenograft model at low drug dose levels. One of these compounds, GDC-0032 (11l), was progressed to clinical trials and is currently under phase I evaluation as a potential treatment for human malignancies.

MOLECULES AND COMPOSITIONS THAT INHIBIT GRAM NEGATIVE BACTERIA AND THEIR USES

Antivirulence strategies to combat Pseudomonas aeruginosa, are described. One strategy encompasses synthesis of a series of compounds that inhibit the production of pyocyanin, a redox-active virulence factor produced by this pathogen. A related strategy e

NEW AZIRIDINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE AS ACETYL-COA CARBOXYLASE INHIBITORS

The invention relates to new azetidine derivatives of the formula (I) wherein Ar1, Ar2, X, R, T and L are as defined in the description, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

AZETIDINE DERIVATIVES

Azetidine derivatives of which the following is exemplary and their use in the treatment of obesity, diabetes or dyslipidemia.

TRICYCLIC HETEROCYCLIC COMPOUNDS

Disclosed are compounds of Formula (I) or stereoisomers or salts thereof, wherein: X1, X2, X3, W, Q1, Q2, and G2 are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and where (i) X1 is N and X2 is S, (ii) X1 is S and X2 is N, (iii) X1 is CR7 and X2 is S, (iv) X1 is S and X2 is CR7; (v) X1 is NR8 and X2 is N, (vi) X1 is N and X2 is NR8, (vii) X1 is CR7 and X2 is O, (viii) X1 is O and X2 is CR7, (ix) X1 is CR7 and X2 is C(R7)2, (x) X1 is C(R7)2 and X2 is CR7; (xi) X1 is N and X2 is O, or (xii) X1 is O and X2 is N, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Rational design of phosphoinositide 3-kinase inhibitors that exhibit selectivity over the phosphoinositide 3-kinase isoform

Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3K has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K vs PI3K selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K that is not attained with the corresponding Lys777 of PI3K. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

BENZOPYRAN AND BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

OXAZOLIDINONE DERIVATIVES N-SUBSTITUTED BY A BICYCLIC RING, FOR USE AS ANTIBACTERIAL AGENTS

Compounds of formula (I) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compoun

OXAZOLIDINONE DERIVATES N-SUBSTITUTED BY A TRICYCLIC RING, FOR USE AS ANTIBACTERIAL AGENTS

Compounds of formula (I) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compounds of formula (I) as disclosed herein can be used in a variety of applications including use as antibacterial P is a tricyclic ring system as defined in claiml.