1126601-99-7

Basic information

• Product Name: 4-(pyridin-2-ylmethoxy)benzoyl chloride
• Synonyms: 4-(pyridin-2-ylmethoxy)benzoyl chloride
• CAS NO: 1126601-99-7
• Molecular Weight: 247.681
• Mol File: 1126601-99-7.mol

Chemical Properties

• CAS DataBase Reference: 4-(pyridin-2-ylmethoxy)benzoyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(pyridin-2-ylmethoxy)benzoyl chloride(1126601-99-7)
• EPA Substance Registry System: 4-(pyridin-2-ylmethoxy)benzoyl chloride(1126601-99-7)

Safety Data

• Hazardous Substances Data: 1126601-99-7(Hazardous Substances Data)

Upstream product

• 120-47-8 Ethyl 4-hydroxybenzoate 
• 6959-47-3 2-chloromethylpyridine hydrochloride 
• 50596-38-8 ethyl 4-(pyridin-2-ylmethoxy)benzoate 
• 1126367-76-7 4-(pyridin-2-ylmethoxy)benzoic acid hydrochloride 
• 50596-36-6 4-(pyridin-2-ylmethoxy)benzoic acid 

Downstream Products

• 1126369-79-6 N-(5-bromo-4-fluoro-2-methylphenyl)-4-(pyridin-2-ylmethoxy)benzamide 
• 1126369-40-1 N-(5-cyano-2-methylphenyl)-4-(pyridin-2-ylmethoxy)benzamide 
• 1126369-57-0 N-(5-bromo-4-chloro-2-methylphenyl)-4-(pyridin-2-ylmethoxy)benzamide 
• 1126408-37-4 N-(5-(1H-benzo[d]imidazol-2-yl)-2-methylphenyl)-4-(pyridin-2-ylmethoxy)benzamide 
• 1126367-42-7 N-(4-fluoro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(pyridin-2-ylmethoxy)benzamide 
• 1126367-36-9 N-(4-chloro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(pyridin-2-ylmethoxy)benzamide 
• 1126368-33-9 N-[4-chloro-5-(1H-imidazol-2-yl)-2-methylphenyl]-4-(pyridin-2-ylmethoxy)benzamide 
• 1126366-38-8 N-[4-chloro-2-methyl-5-(1-methyl-1H-imidazol-4-yl)phenyl]-4-(pyridin-2-ylmethoxy)benzamide 
• 1126368-35-1 N-[4-chloro-5-(1,2-dimethyl-1H-imidazol-4-yl)-2-methylphenyl]-4-(pyridin-2-ylmethoxy)benzamide 
• 1126368-31-7 N-[4-chloro-2-methyl-5-(1-methyl-1H-imidazol-2-yl)phenyl]-4-(pyridin-2-ylmethoxy)benzamide 

Relevant articles and documents

Heteroarylamide smoothened inhibitors: Discovery of N-[2,4-dimethyl-5-(1-methylimidazol-4-yl)phenyl]-4-(2-pyridylmethoxy)benzamide (AZD8542) and N-[5-(1H-imidazol-2-yl)-2,4-dimethyl-phenyl]-4-(2- pyridylmethoxy)benzamide (AZD7254)

Aberrant hedgehog (Hh) pathway signaling is implicated in multiple cancer types and targeting the Smoothened (SMO) receptor, a key protein of the Hh pathway, has proven effective in treating metastasized basal cell carcinoma. Our lead optimization effort focused on a series of heteroarylamides. We observed that a methyl substitution ortho to the heteroaryl groups on an aniline core significantly improved the potency of this series of compounds. These findings predated the availability of SMO crystal structure in 2013. Here we retrospectively applied quantum mechanics calculations to demonstrate the o-Me substitution favors the bioactive conformation by inducing a dihedral twist between the heteroaryl rings and the core aniline. The o-Me also makes favorable hydrophobic interactions with key residue side chains in the binding pocket. From this effort, two compounds (AZD8542 and AZD7254) showed excellent pharmacokinetics across multiple preclinical species and demonstrated in vivo activity in abrogating the Hh paracrine pathway as well as anti- tumor effects.

HETEROCYCLIC AMIDES USEFUL FOR THE TREATMENT OF CANCER AND PSORIASIS

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. Formula (IA) with the provisio that either R2or R3 is (Z).