On December 7, 2017, Kato, Taku; Sakamoto, Toshiaki; Niwa, Yasuki; Sawamoto, Daisuke; Otani, Naohito; Kanbe, Misaki published a patent.COA of Formula: C9H14N2 The title of the patent was Preparation of aromatic carboxylic acid amides having TRPM8 blocking effect. And the patent contained the following:
Disclosed are compounds I [ring A = benzene or thiophene; X1 = CR11 or nitrogen atom; R11 = H or (un)substituted alkyl; X2, X3 = independently CH or nitrogen atom; ring C = monocyclic ring; R1 = (un)substituted alkyl, (un)substituted alkanoyl, cyano, etc.; R1 is substituted on the adjacent position to the point of attachment to ring B; R2 = H, (un)substituted alkyl or halo; R3 = cyano, -Ra, -N(Rb)(Rc), etc.; Ra = (un)substituted alkyl, (un)substituted non-aromatic heterocycle-methyl-, (un)substituted alkenyl, etc.; Rb = (un)substituted alkyl, (un)substituted alkenyl, (un)substituted cycloalkyl, etc.; Rc = H, (un)substituted alkyl, (un)substituted alkenyl, etc.; R4 = (un)substituted alkyl, (un)substituted alkanoyl, cyano, etc.; n = 0 or 1; R5 = H, (un)substituted alkyl, hydroxy, etc.; when n is 1, R4 and R5, together with ring C, may combine to form a bicyclic ring; or pharmacol. acceptable salts thereof]. For example, compound II was prepared from 5-bromo-3-fluoropyridine-2-carboxylic acid Et ester via conversion into 3-iodo-5-[2-(trifluoromethyl)phenyl]pyridine-2-carboxylic acid followed by amidation with 5-amino-2-trifluoromethylpyridine and reaction with 5-methyl-2-pyrrolidone. In TRPM8 blocking test, 361-example of I showed IC50 values (nmol/L) ranging from 0.2 to 2760, e.g., IC50 of II was 4 nmol/L. Of note, compounds I are useful for the treatment of chronic pain. The experimental process involved the reaction of 6-(tert-Butyl)pyridin-3-amine(cas: 39919-70-5).COA of Formula: C9H14N2
The Article related to aromatic carboxylic acid amide preparation trpm8 blocker, chronic pain treatment aromatic carboxylic acid amide trpm8 blocking, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.COA of Formula: C9H14N2