958646-69-0

Usage

Uses

Used in Pharmaceutical Industry:
(5-aMino-2-chlorophenyl)boronic acid is used as a reagent for the preparation of benzothiazoles, pyridopyrimidines, and related compounds. These compounds are of significant interest in the pharmaceutical industry as they serve as KRAS G12C inhibitors. KRAS G12C is a mutation found in various cancers, and inhibiting its activity can help in the development of targeted cancer therapies.

Upstream product

• 867333-29-7 (2-chloro-5-nitrophenyl)boronic acid 
• 74534-15-9 1-chloro-2-iodo-4-nitrobenzene 
• 6283-25-6 H₂NC₆H₃(Cl)NO₂ 
• 573764-31-5 3-iodo-4-chloroaniline 
• 73183-34-3 bis(pinacol)diborane 

Downstream Products

• 1007224-62-5 7-(5-amino-2-chloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine 
• 1128191-81-0 4-chloro-3-(2-methylimidazo[1,2-a]pyridin-3-yl)aniline 
• 1128191-78-5 [2-chloro-5-({[2-methyl-6-(trifluoromethyl)pyridin-3-yl]carbonyl}amino)phenyl]boronic acid 
• 1128191-82-1 4-chloro-3-(1,5-dimethylimidazol-2-yl)aniline 
• 1128191-85-4 (S)-2-chloro-5-(6-((1-methylpyrrolidin-2-yl)methoxy)nicotinamido)phenylboronic acid 
• 879088-41-2 4-chloro-3-(pyridin-2-yl)benzeneamine 

Relevant academic research and scientific papers

Design, Synthesis, and Structure-Activity Relationship of Tetrahydropyrido[4,3-d]pyrimidine Derivatives as Potent Smoothened Antagonists with in Vivo Activity

Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its nonlinear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility. Many patients experience adverse events such as muscle spasms and weight loss. In addition, drug resistance often arises among tumor cells during treatment with vismodegib. There is clearly an urgent need to explore novel Smo antagonists with improved potency and efficacy. Through a scaffold hopping strategy, we have identified a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives, which exhibited effective inhibition of Hh signaling. Among them, compound 24 is three times more potent than vismodegib in the NIH3T3-GRE-Luc reporter gene assay. Compound 24 has a lower melting point and much greater solubility compared with vismodegib, resulting in linear PK profiles when dosed orally at 10, 30, and 100 mg/kg in rats. Furthermore, compound 24 showed excellent PK profiles with a 72% oral bioavailability in beagle dogs. Compound 24 demonstrated overall favorable in vitro safety profiles with respect to CYP isoform and hERG inhibition. Finally, compound 24 led to significant regression of subcutaneous tumor generated by primary Ptch1-deficient medulloblastoma cells in SCID mouse. In conclusion, tetrahydropyrido[4,3-d]pyrimidine derivatives represent a novel set of Smo inhibitors that could potentially be utilized to treat medulloblastoma and other Hh pathway related malignancies.

HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF-975

The present disclosure relates to heterocyclic amide compounds, which are useful for inhibiting the Hedgehog pathway, and their use in treating a disease or medical condition mediated alone or in part by Hedgehog pathway inhibition. Also disclosed are methods for manufacture of these compounds, pharmaceutical compositions including these compounds, and use of these compounds in the manufacture of medicaments for treating such diseases and medical conditions in a subject.