The invention belongs to the pharmaceutical manufacturing field, which relates to a novel process for the preparation of substituted phenylacetic acids derivatives, especially relates to the preparation of 2-(4-(2-oxocyclopentyl)phenyl)propanoic acid. The process for the preparation of the precursor form of loxoprofen which use 1,4-di-halobenzyl compounds or disubstituted benzyl compounds as starting material, is through the substitution reaction of cyclopentanone groups or its precursor compounds.

##STR00001##

Wherein X is halogen, L.sub.1 is a suitable leaving group selected from halogen, OH, OMs, OTs, OTf and the like; L.sub.2 is a suitable leaving group selected from halogen, CN, OH, CH.sub.2OH, CHO, CH.sub.3NO.sub.2, ester group, NR.sub.4R.sub.5, OTf, OTs, OMs, CCR.sub.6, CCR.sub.7 and the like, wherein R.sub.4, R.sub.5, R.sub.6, R.sub.7 are short chain alkyl groups; Z is cyclopentanone group and its precursor form selected from

##STR00002##

and the like; R.sub.3 is short chain alkyl groups. L.sub.3 is a suitable leaving group selected from halogen, OH, OMs, OTs, OT.sub.f and the like, or organometallic groups. The invention also include the detailed procedure to convert the precursor compounds of cyclopentanone group to cyclopentanone, followed by the transformation of the precursor compounds of loxoprofen to loxoprofen.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

The present invention relates to a compound of formula (I), or a tautomer, stereoisomer, geometrical isomer, prodrug, carboxylic acid isostere, solvate, polymorph, N-oxide, S-oxide or pharmaceutically acceptable salt thereof, which are GPR120 agonists. The present invention also relates to a pharmaceutical composition of a compound of formula (I) for the treatment of metabolic disorders, particularly Type 2 diabetes and associated diseases. ##STR00001##

The present invention relates to a compound of formula (I), or a tautomer, stereoisomer, geometrical isomer, prodrug, carboxylic acid isostere, solvate, polymorph, N-oxide, S-oxide or pharmaceutically acceptable salt thereof, which are GPR120 agonists. The present invention also relates to a pharmaceutical composition of a compound of formula (I) for the treatment of metabolic disorders, particularly Type 2 diabetes and associated diseases. ##STR00001##

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

The present disclosure is generally directed to compositions and methods for treating diseases that are ameliorated by the inhibition of CYP26 mediated retinoic acid metabolism. The compositions comprise compounds of formula (I). A repreid50000060307390 IB/345 nullsents aryl optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, NH.sub.2, NH(C.sub.1-C.sub.6 alkyl), N(C.sub.1-C.sub.6 alkyl).sub.2, OH, C.sub.1-C.sub.6 alkoxy, and C.sub.1-C.sub.6 haloalkoxy; X is a bond, CH.sub.2, CHR.sup.5, CCHR.sup.4, NR.sup.4, NOR.sup.4, O, S, SO, SO.sub.2, C(O), or C(NR.sup.4), or X is of formula (a), (b) or (c), wherein each n is independently 1, 2, or 3; each R.sup.4 is independently hydrogen or C.sub.1-6 alkyl; R.sup.5 is independently hydrogen, C.sub.1-6 alkyl, or OR.sup.6, where R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyL C.sub.3-12 cycloalkyl, heterocyclyl, aryl, arylC.sub.1-6 alkyl, heteroaryl, or heteroarylC.sub.1-6 alkyl; Y is C.sub.1-6 alkylene, C.sub.2-6 alkenylene, or C.sub.2-6 alkylylene moiety. ##STR00001##

The present disclosure is generally directed to compositions and methods for treating diseases that are ameliorated by the inhibition of CYP26 mediated retinoic acid metabolism. The compositions comprise compounds of formula (I). A repreid50000060307390 IB/345 nullsents aryl optionally substituted with one, two, three, or four groups that are each independently halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, NH.sub.2, NH(C.sub.1-C.sub.6 alkyl), N(C.sub.1-C.sub.6 alkyl).sub.2, OH, C.sub.1-C.sub.6 alkoxy, and C.sub.1-C.sub.6 haloalkoxy; X is a bond, CH.sub.2, CHR.sup.5, CCHR.sup.4, NR.sup.4, NOR.sup.4, O, S, SO, SO.sub.2, C(O), or C(NR.sup.4), or X is of formula (a), (b) or (c), wherein each n is independently 1, 2, or 3; each R.sup.4 is independently hydrogen or C.sub.1-6 alkyl; R.sup.5 is independently hydrogen, C.sub.1-6 alkyl, or OR.sup.6, where R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyL C.sub.3-12 cycloalkyl, heterocyclyl, aryl, arylC.sub.1-6 alkyl, heteroaryl, or heteroarylC.sub.1-6 alkyl; Y is C.sub.1-6 alkylene, C.sub.2-6 alkenylene, or C.sub.2-6 alkylylene moiety. ##STR00001##

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

Provided is a process for making non-phthalate plasticizers, by acylating an aromatic compound with a succinic anhydride to form a keto-acid, and then esterifying the keto-acid with C.sub.4-C.sub.13 OXO-alcohols to form a plasticizer compound. The aromatic rings of the aromatic compound may also be optionally hydrogenated.