Phthalazine derivatives for treating inflammatory diseases

A compound of formula I,

• wherein
• r is 0 to 2,
• n is 0 to 2,
• R1 and R2
• a) are independently in each case a lower alkyl;
• b) together form a bridge of subformula 1*,
• wherein the bond is achieved via the two terminal C atoms and
• m is 0 to 4, or
• c) together form a bridge of subformula 1**,
• wherein one or two of the ring members T1, T2, T3 and T4 are nitrogen, and the others are in each case CH, and the bond is achieved via atoms T1 and T4;
• G represents
• i) C2-C6alkenylene, C2-C6alkylene or C3-C6alkenylene substituted by acyloxy or hydroxy, —CH2—O—, —CH2—S—, —CH2—NH—, —CH2—O—CH2—, —CH2—S—CH2—, —CH2—NH—CH2—, oxa (—O—), thia (—S—), imino (—NH—), —C(═O)—, —CHF— or —CF2—;
• or
• ii) C2-C6alkylene if Q is lower alkyl, or
• iii) C1-C6alkylene if Q is lower alkoxy or halogen;
• A, B, D, E and T are independently N or CH subject to the proviso that at least one and not more than three of these radicals are N, and that T is only N when α) G is C2-C6alkenylene or C3-C6alkenylene substituted by acyloxy or hydroxy, or β) when Q is lower alkoxy or halogen;
• Q is lower alkyl, lower alkoxy or halogen;
• Ra and Ra′ are each independently H or lower alkyl;
• X is imino, oxa, or thia;
• Y is hydrogen, aryl, heteroaryl, or unsubstituted or substituted cycloalkyl;
• and
• Z is mono- or disubstituted amino, halogen, alkyl, substituted alkyl, hydroxy, etherified or esterified hydroxy, nitro, cyano, carboxy, esterified carboxy, alkanoyl, carbamoyl, N-mono- or N,N-disubstituted carbamoyl, amidino, guanidino, mercapto, sulfo, phenylthio, phenyl lower alkylthio, alkylphenylthio, phenylsulfinyl, phenyl-lower alkylsulfinyl, alkylphenylsulfinyl, phenylsulfonyl, phenyl-lower alkylsulfonyl, or alkylphenylsulfonyl, wherein—if more than 1 radical Z (m≧2) is present—the substituents Z are selected independently of each other,
• and wherein the bonds characterized in subformula 1* by a wavy line are either single or double bonds;
• or an N-oxide of said compound, wherein 1 or more N atoms carry an oxygen atom;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula IA

• wherein
• r is 0 to 2, especially 0 or 1;
• n is 0 to 3;
• R1 and R2 together form a bridge as shown in subformula 1***,
• wherein either each of Z1 and Z2 is hydrogen, or one is hydrogen, the other methyl;
• the binding being achieved via the two terminal CH groups in subformula 1*** and to the two adjacent carbon atoms binding R1 and R2 in formula IA, so that a six-membered ring is formed;
• A, B, D and E are CH and T is N,
• Q is methyl (preferably bound to A and/or D);
• G is —C(═O)—, —CHF— or —CF2—;
• each of Ra and Ra′ is hydrogen;
• X is imino;
• Y is 4-chlorophenyl, 4-tert-butyl-phenyl, 3,5-dimethyl-phenyl, 2-methyl-6-ethyl-phenyl, 3-isopropyl-5-methyl-phenyl, 3-ureido-phenyl, 3-chloro-4-methoxy-phenyl, 4-chloro-3-methoxy-phenyl, 3-methoxy-4-methyl-phenyl, 3-methoxy-4-ethyl-phenyl, 3-(trifluoro-methylthio)-phenyl, 6-chloro-3-(trifluoromethylsulfonyl)-phenyl, 3-(N-methylcarbamoyl)-phenyl, 4-(N-tert-butylcarbamoyl)-phenyl, 3-(pyrazol-3-yl)-phenyl, 3-([1-methyl-pyrazol]-3-yl)-phenyl, 4-tert-butoxycarbonyl)-phenyl, 3,5-bis(methoxycarbonyl)-phenyl, 3-vinyl-phenyl, 3,4- or 3,5-bis(trifluoromethyl)-phenyl, 3-chloro-4-methyl-phenyl, 3-bromo-4-methyl-phenyl, bromo-4-ethyl-phenyl, 4-bromo-3-isopropyl-phenyl, 4-bromo-3-n-propyl-phenyl, 3-iodo-4-methylphenyl, 4-iodo-3-isopropyl-phenyl, 4-fluoro-3-trifluoromethyl-phenyl, 3-chloro-5-trifluoromethyl-phenyl, 4-chloro-3-trifluoromethyl-phenyl, 3-bromo-5-trifluoromethyl-phenyl, 4-bromo-3-trifluoromethyl-phenyl, 4-iodo-3-trifluormethyl-phenyl, 3-bromo-5-(2,2,2-trifluoroethyl)-phenyl, 3-iodo-5-trifluoromethyl-phenyl, 3-methyl-5-trifluoromethylphenyl or sulfamoyl-phenyl,
• or (especially if n is other than 0) is 4-methylphenyl, 3-methylphenyl, 4-ethyl-phenyl, 3-ethyl-phenyl, 2-methylphenl, 3- or 4-trifluoromethyl-phenyl, 2-chlorophenyl, 3-chlorophenyl or 3-fluoro-5-trifloromethyl-phenyl,
• or is 2-naphthyl;
• quinolin-6-yl;
• 5-ethyl-pyridin-2-yl;
• 6-methyl-pyridin-2-yl;
• 4-methylpyrimidin-2-yl;
• 6-tert-butyl-pyrimidin-4-yl;
• 5-trifluoromethyl-pyridin2-yl;
• 5-methoxy-pyridin-2-yl;
• 2,6-dimethyl-pyridin-4- or 4,6-dimethyl-pyridin-2-yl;
• 2,6-dimethyl-pyrimidin-4-yl;
• 5-bromo-pyridin-2-yl or 6-chloro-pyridin-3-yl;
• or is 4-tertbutylcyclohexyl;
• or an N-oxide thereof, wherein 1 or more nitrogen atoms carry an oxygen atom;
• or a salt thereof.