Phenylalkyloxy-phenyl derivatives

A compound of the general formula (I)

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• and stereo and optical isomers and racemates thereof as well as pharmaceutically acceptable salts, prodrugs, solvates and crystalline forms thereof, in which formula a is situated in the ortho, meta or para position and represents
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• wherein r is cyano, when x is 0, and when x is I then r is:
• —BRa, OCORa or SCORa, wherein B is O, S, SO or SO2 wherein Ra represents hydrogen, alkyl, aryl, alkylaryloxy or alkylaryl and wherein the alkyl, aryl or alkylaryl group is optionally substituted one or more times by Rb, wherein Rb represents alkyl, aryl, alkylaryl, cyano, —NRcRc, ═O, halogen, —OH, —SH, -Oalkyl, -Oaryl, -Oalkylaryl, —CORc, —SRd, —SORd, or —SO2Rd (preferably Rb is selected from alkyl, aryl, alkylaryl, cyano, —NH2, ═O, halogen and —OH), wherein Rc represents hydrogen, alkyl, aryl or alkylaryl and Rd represents alkyl, aryl or alkylaryl;
• —BB1Ra, wherein B1 is O when B is S, SO or SO2 or B1 is S, SO or SO2 when B is O, and wherein B and Ra are as defined above;
• or alternatively R is —NRaRa, wherein each Ra is the same or different and wherein Ra is defined above;
• R2 represents alkyl, halogen, aryl, alkylaryl, alkenyl, alkynyl, nitro or cyano and wherein the alkyl, aryl, alkenyl, alkylaryl and alkynyl group is optionally substituted by Rb, wherein Rb is as defined above;
• —BRa wherein B and Ra are as defined above;
• —SO2NRaRf, wherein Rf represents hydrogen, alkyl, acyl, aryl or alkylaryl and Ra is as defined above;
• —SO2ORa, wherein Ra is as defined above;
• —OCONRfRa, wherein Rf and Ra are as defined above;
• —NRcCOORd, wherein Rc and Rd are as defined above;
• —NRcCORa, wherein Rc and Ra are as defined above;
• —CONRcRa, wherein Rc and Ra are as defined above;
• —NRcSO2Rd, wherein Rc and Rd are as defined above;
• —NRcCONRaRk, wherein Ra and Rc are as defined above and Rk represents hydrogen, alkyl, aryl, or alkylaryl;
• alternatively R2 is —NRcRa, wherein Rc and Ra are as defined above;
• R1, R3 and R4 are the same or different and each represents hydrogen, alkyl, aryl, alkenyl, alkynyl, cyano, halogen or alkylaryl wherein the alkyl, aryl, alkenyl or alkynyl group is optionally substituted by Rb;
• x is an integer 0 or 1 (preferably x is 1);
• E represents a group of formula i
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• or a group of formula ii
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• wherein X is S, O, NRZ wherein RZ is as defined below, CH═N or N═CH and Y represents CH or N;
• or X represents —CH═CH— and Y represents N;
• or E represents a group of formula iii
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• wherein X is S, O, NRz, —CH═N or —N═CH and Y represents CH or N;
• or X represents —CH═CH— and Y represents N wherein Rz represents hydrogen, alkyl, aryl, alkyloxyaryl, alkylbiphenylyl, alkoxyalklylaryl, acylbiphenylyl, alkylphthalimido, SO2RZ, CORd or alkylaryl (preferably RZ is selected from hydrogen, alkyl and alkyaryl) and wherein the alkyl, aryl, alkyloxyaryl or alkylaryl group is optionally substituted one or more times by Rb, wherein Rb represents alkyl, aryl, alkylaryl, cyano, —NRcRc, ═O, halogen, —OH, —SH, -Oalkyl, -Oaryl, -Oalkylaryl, —CORc, —SRd, —SORd, or —SO2Rd (preferably Rb is selected from alkyl, aryl, alkylaryl, cyano, —NH2, ═O, halogen and —OH), wherein Rc represents hydrogen, alkyl, aryl or alkylaryl and Rd represents alkyl, aryl or alkylaryl;
• or E represents a group of formula iv
• C3-C8cycloalkyl iv
• or E represents a group of formula v
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• which is linked to L through the nitrogen atom;
• or E represents a group of formula vi
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• or E represents a group of formula vii
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• wherein D represents H, alkyl, acyl, aryl, alkylaryl, halogen, —CN and NO2, wherein the alkyl, aryl, or alkylaryl group is optionally substituted by Rb;
• —NRcCOORa, wherein Rc and Ra are as defined above;
• —NRcCORa, wherein Rc and Ra are as defined above;
• —NRcRa, wherein Rc and Ra are as defined above;
• —NRcSO2Rd, wherein Rc and Rd are as defined above;
• —NRcCONRkRc, wherein Ra, Rc and Rk are as defined above;
• —NRcCSNRaRk, wherein Ra, Rc and Rk are as defined above;
• —ORa, wherein Ra is as defined above;
• —OSO2Rd, wherein Rd is as defined above;
• —SO2Rd, wherein Rd is as defined above;
• —SORd, wherein Rd is as defined above;
• —SRc, wherein Rc is as defined above;
• —SO2NRaRf, wherein Rf and Ra are as defined above;
• —SO2ORa, wherein Ra is as defined above;
• —CONRcRa, wherein Rc and Ra are as defined above;
• —OCONRfRa, wherein Rf and Ra are as defined above;
• m is an integer 0 or 1 (preferably m is 1);
• D′ represents hydrogen, alkyl, acyl, aryl, alkylaryl, halogen, —CN, —NO2, —NRfRb, wherein Rf and Rb are as defined above;
• —ORf, wherein Rf is as defined above;
• —OSO2Rd, wherein Rd is as defined above;
• CH═CH—COORc wherein Rc is as defined above;
• D″ is represents hydrogen, alkyl, acyl, aryl, alkylaryl, halogen;
• —CN, —NO2, —NRfRb wherein Rf and Rb are as defined above;
• —ORf, wherein Rf is as defined above;
• —OSO2Rd, wherein Rd is as defined above;
• L represents O or an alkylene chain having from 1 to 6 carbon atoms optionally interrupted or terminated by one or more of the following O, S, SO, SO2, CO, NRt, CONRt, NRtCO, OC(O)NRt, NRtC(O)O, SO2NRt, RtNSO2 or RtN—CO—NRt provided that they are not attached to each other and wherein the alkylene chain carbons may be substituted by one or more alkyl, hydroxy, aryl, aryloxy, arylthio, alkylaryl, cyano, NRcRc, halo, SH, Oalkylaryl, CORc, —CORc, —SRd, —SORd, or —SO2Rd, or alkoxy and with the proviso that when E is a group of formula i then L does not represent [CH2]n—CH2—O in which n is an integer from 1 to 6;
• and Rt represents H, alkyl, aryl, alkylaryl, alkylcycloalkyl, or alkylbiphenylyl wherein each alkyl chain may be substituted by one or more hydroxy or alkoxy and is optionally interrupted by one or more O provided that two hetero atoms are not attached to the same carbon atom.