Derivatives of naphthalene with COMT inhibiting activity

A pharmaceutical composition which comprises as an active agent a compound of formula I′:

• wherein the two OH— substituents in the phenyl moiety are in a position ortho to one another and R1 is in a position ortho to one of the hydroxy groups;
• and
• wherein
• “A” is a fused ring moiety selected from a benzo ring and a 6-membered heteroaromatic ring which contains one or two N heteroatoms;
• R1 is NO2, CN, CHO, CF3 or (C1-C6)alkyl-CO—;
• t is 0, 1,2,3 or 4;
• each R2 is selected independently from OH, halogen, NO2, SH, NH2, (C1-C6)alkyl, (C2C5)alkenyl, (C1-C6)alkoxy, OH—(C1-C6)alkyl, NH2—(C1-C6)alkyl, halo-(C1-C6)alkyl, mono- or di(C1-C6)alkylamino, SO2R4, (C1-C20)alkyl-CO—, halo-(C1-C6)alkyl-CO—, phenyl-N═N— optionaliy substituted with one to three substituents R6, —(Y)n—(B)m—COOH and —(Y)n—(B)m—R5;
• R3 is H, NO2, CN, CHO, halogen, CF3 or (C1-C6)alkyl;
• and
• R4 is (C1-C6)alkyl, NH2, OH or mono- or di(C1-C6)alkylamino;
• m is 0 or 1;
• n is 1;
• Y is —CO— or —CHOH—;
• B is (C1-C6)alkylene or (C2-C6)alkenylene;
• R5 is phenyl, naphthyl, (C3-C7)cycloalkyl or 5- to 10-membered heterocyclyl with one to four heteroatoms each selected independently from N, O and S, wherein the said phenyl, naphthyl, (C3-C7)cycloalkyl or 5- to 10-membered heterocyclyl is optionally substituted with one to five substituents R6;
• or R5 is
• each R6 is selected independently from OH, halogen, COOH, 5-tetrazolyl, NO2, SH, NH2, CN, CHO, ═O, (C1-C6)alkyl, (C1-C6)alkoxy, halo-(C1-C6)alkyl, mono- or di(C1-C6)alkylamino, CO—(C1-C6)alkyl, CO—NH2, mono- or di(C1-C6)alkylamino-CO—, NHOH, CONHOH and SO2R4;
• or a pharmaceutically acceptable salt or pharmaceutically acceptable ester or pharmaceutically acceptable amide thereof, and a pharmaceutically acceptable excipient.

A method for treating Parkinson's Disease, which comprises administering to a mammal in need of the treatment an effective amount of levodopa and an effective amount of the compound of formula I′:

• wherein the two OH— substituents in the phenyl moiety are in a position ortho to one another and R1 is in a position ortho to one of the hydroxy groups;
• and
• wherein
• “A” is a fused ring moiety selected from a benzo ring and a 6-membered heteroaromatic ring which contains one or two N heteroatoms;
• R1 is NO2, CN, CHO, CF3 or (C1-C6)alkyl-CO—;
• t is 0, 1,2,3 or 4;
• each R2 is selected independently from OH, halogen, NO2, SH, NH2, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkoxy, OH—(C1-C6)alkyl, NH2—(C1-C6)alkyl, halo-(C1-C6)alkyl, mono- or di(C1-C6)alkylamino, SO2R4,(C1-C20)alkyl-CO—, halo-(C1-C6)alkyl-CO—, phenyl-N═N- optionally substituted with one to three substituents R6,—(Y)n—(B)m—COOH and —(Y)n—(B)m—R5;
• R3 is H, NO2, ON, CHO, halogen, CF3 or (C1-C6)alkyl;
• and
• R4 is (C1-C6)alkyl, NH2, OH or mono- or di(C1-C6)alkylamino;
• m is 0 or 1;
• n is 1;
• Y is —CO— or —CHOH—;
• B is (C1-C6)alkylene or (C2-C6)alkenylene;
• R5 is phenyl, naphthyl, (C3-C7)cycloalkyl or 5- to 10-membered heterocyclyl with one to four heteroatoms each selected independently from N, O and S, wherein the said phenyl, naphthyl, (C3-C7)cycloalkyl or 5- to 10-membered heterocyclyl is optionally substituted with one to five substituents R6
• or R5 is
• each R6 is selected independently from OH, halogen, COOH, 5-tetrazolyl, NO2,SH, NH2, CN, CHO, ═O , (C1-C6)alkyl, (C1-C6)alkoxy, halo-(C1-C6)alkyl, mono- or di(C1-C6)alkylamino, CO—(C1-C6)alkyl, CO—NH2, mono- or di(C1-C6)alkylamino-CO—, NHOH, CONHOH and SO2R4;
• or pharmaceutically acceptable salt or pharmaceutically acceptable ester or pharmaceutically acceptable amide thereof to potentiate the levodopa therapy.