On December 1, 2005, Epple, Robert; Russo, Ross; Azimioara, Mihai; Xie, Yongping published a patent.Safety of Methyl 2-(3-formylphenyl)acetate The title of the patent was Isoxazole compounds as PPAR modulators, their preparation, pharmaceutical compositions, and use in therapy. And the patent contained the following:
The invention relates to isoxazole compounds of formula I, which are modulators of peroxisome proliferator-activated receptors (PPAR), particularly PPARδ. In compounds I, R1 is selected from (un)substituted C1-6 alkyl, (un)substituted C3-12 cycloalkyl, (un)substituted C3-8 heterocyclyl, (un)substituted C6-10 aryl, and (un)substituted C5-10 heteroaryl; R2 is selected from (CH2)nO(CH2)nOR5, (CH2)nOR5, CO2R5, C(O)N(R4)2, C(O)N(R4)(CH2)nOR4, CO2(CH2)nOR5, C(O)(CH2)nOR5, C(O)N(R4)(CH2)nOR5, C(O)N(R4)(R5), and C(O)N(R4)(CH2)nR5, where n is 0-4, R4 is H or C1-6 alkyl, and R5 is C1-6 alkyl, C3-12 cycloalkyl, C3-8 heterocyclyl, C6-10 aryl, or C5-10 heteroaryl, or R4 and R5, together with the nitrogen atom to which they are attached, form C3-8 heterocyclyl or C5-10 heteroaryl; and R3 is selected from (un)substituted C3-12 cycloalkyl, (un)substituted C3-8 heterocyclyl, (un)substituted C6-10 aryl, and (un)substituted C5-10 heteroaryl; including pharmaceutically acceptable salts, hydrates, solvates, isomers, and prodrugs thereof. The invention also relates to the preparation of I, pharmaceutical compositions comprising a therapeutically effective amount of compound I in combination with one or more pharmaceutically acceptable excipients, as well as to the use of the compositions to treat or prevent diseases or disorders associated with PPAR activity. Esterification of 3-bromophenylacetic acid followed by coupling with cyanide, reduction of the nitrile to an aldehyde, condensation with hydroxylamine, and chlorination gave chlorooxime II. N-Boc-2-bromoethylamine was substituted with 2,4-dichlorophenol followed by deprotection, amidation with Et benzoylacetate to give benzoylacetamide III, which underwent cyclocondensation with chlorooxime II and ester hydrolysis, resulting in the formation of isoxazole IV. Most preferred compounds of the invention express an EC50 value for PPARδ of less than 100 nM. The compounds of the invention are at least 100-fold selective for PPARδ over PPARγ. The experimental process involved the reaction of Methyl 2-(3-formylphenyl)acetate(cas: 142327-44-4).Safety of Methyl 2-(3-formylphenyl)acetate
The Article related to isoxazole preparation selective ppar delta modulator, Heterocyclic Compounds (More Than One Hetero Atom): Oxazoles, Isoxazoles and other aspects.Safety of Methyl 2-(3-formylphenyl)acetate
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics