Aza compounds, pharmaceutical compositions and methods of use

A pharmaceutical composition comprising:

• (i) a therapeutically effective amount of a compound of formula I:
• or a pharmaceutically acceptable salt or ester thereof, wherein:
• n=1-3;
• R1 is selected from the group consisting of —C(R3)3, —COOR3, —COR3, —COOH, —SO3H, —SO2HNR3, —PO2(R3)2, —CN, —PO3(R3)2, —OR3, —SR3, —NHCOR3, —N(R3)2, —CON(R3)2, —CONH(O)R3, —CONHNHSO2R3, —COHNSO2R3, and —CONR3CN;
• R2 is selected from the group consisting of hydrogen, C1-C9 straight or branched chain alkyl, C12-C19 straight or branched chain alkenyl, C12-C19 straight or branched chain alkynyl, aryl, heteroaryl, carbocycle, and heterocycle, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocycle, and heterocycle is unsubstituted or substituted with one or more substituents selected from R3;
• R3 is selected from the group consisting of hydrogen, C1-C9 alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, C1-C9 alkoxy, C2-C9 alkenyloxy, aryloxy, phenoxy, benzyloxy, hydroxy, carboxy, C1-C9 thioalkyl, C2-C9 thioalkenyl, C1-C9 alkylamino, C2-C9 alkenylamino, cyano, nitro, imino, sulfonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, and heterocycle,
• wherein said alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryloxy, thioalkyl, thioalkenyl, alkylamino, alkenylamino, aryl, heteroaryl, carbocycle, or heterocycle group is optionally substituted with a hydroxy, carboxy, cyano, nitro, imino, sulfonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocyle, or heterocycle group;
• and
• X is O or S;
• and
• (ii) a pharmaceutically acceptable carrier,
• wherein the heteroaryl, carbocycle, and heterocycle are selected from cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, indolyl, isoindolyl, indolinyl, benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzthiazolyl, tetrahydrofuranyl, tetrahydropyranyl, pyridyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, purinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinolizinyl, furyl, thiophenyl, imidazolyl, oxazolyl, benzoxazolyl, thiazolyl, isoxazolyl, isotriazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, trithianyl, indolizinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thienyl, tetrahydroisoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, adamantly, pyrrole groups, thiophene groups, pyridine groups, and isoxazole groups.

A method for treating peripheral neuropathy or Parkinson's disease in a mammal, comprising administering to the mammal an effective amount of a compound of formula I:

• or a pharmaceutically acceptable salt or ester thereof, wherein:
• n=1-3;
• R1 is selected from the group consisting of—C(R3)3, —COOR3, —COR3, —COOH, —SO3H, —SO2HNR3, —PO2(R3)2, —CN, —PO3(R3)2, —OR3, —SR3, —NHCOR3, —N(R3)2, —CON(R3)2, —CONH(O)R3, —CONHNHSO2R3, —COHNSO2R3, and —CONR3CN;
• R2 is selected from the group consisting of hydrogen, C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, aryl, heteroaryl, carbocycle, and heterocycle, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocycle, and heterocycle is unsubstituted or substituted with one or more substituents selected from R3;
• R3 is selected from the group consisting of hydrogen, C1-C9 alkyl, C2-C9 straight or branched chain alkenyl, C2-C9 straight or branched chain alkynyl, C1-C9 alkoxy, C2-C9 alkenyloxy, aryloxy, phenoxy, benzyloxy, hydroxy, carboxy, C1-C9 thioalkyl, C2-C9 thioalkenyl, C1-C9 alkylamino, C2-C9 alkenylamino, cyano, nitro, imino, sulfonyl, suithydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocycle, and heterocycle,
• wherein said alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryloxy, thioalkyl, thioalkenyl, alkylamino, alkenylamino, aryl, heteroaryl, carbocycle, or heterocycle group is optionally substituted with a hydroxy, carboxy, cyano, nitro, imino, sulfonyl, sulfhydryl, halo, haloalkyl, trifluoromethyl, aryl, heteroaryl, carbocyle, or heterocycle group;
• and
• X is O or S,
• wherein the heteroaryl, carbocycle, and heterocycle are selected from cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, indolyl, isoindolyl, indolinyl, benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzthiazolyl, tetrahydrofuranyl, tetrahydropyranyl, pyridyl, pyrrolyl, pyrrolidinyl, pyridinyl, pyrimidinyl, purinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinolizinyl, furyl, thiophenyl, imidazolyl, oxazolyl, benzoxazolyl, thiazolyl, isoxazolyl, isotriazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, trithianyl, indolizinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thienyl, tetrahydroisoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, adamantly, pyrrole groups, thiophene groups, pyridine groups, and isoxazole groups.