Patent ID: 6747024
Filing Date: 2004-06-08
Classification: A61P,C07D

Abstract:
A compound of the formula in racemic, enantiomeric or diastereoisomeric form and all combinations of these forms, whereinR1 is selected from the group consisting of hydrogen, â€”OR3, â€”SR3, oxo and cyclic acetal, R3 is selected from the group consisting of hydrogen, alkyl, aralalkyl, heterocycloalkylcarbonyl, alkylcarbonyl, arylcarbonyl and aralkylcarbonyl, the akyl, aryl or heterocycloalkyl unsubstituted or substituted by at least one member selected from the group consisting of alkyl, â€”OH, alkoxy, nitro, cyano, halogen and â€”NR4R5; R4 and R5 are independently selected from the group consisting of hydrogen or alkyl, or R4 and R5 together with the nitrogen atom to which they are attached form an optionally substituted heterocycle, R2 is selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl, the aryl group being unsubstituted or substituted by at least one member selected from the group consisting of â€”OR6, â€”NR7R8, halogen, cyano, nitro and alkyl, R6, R7, and R8 are independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, arylcarbonyl and aralkylcarbonyl, A is wherein R9, R10, R11, R12, R13 are independently selected from the group consisting of hydrogen, halogen, â€”OH, alkyl, alkoxy, cyano, nitro and â€”NR15R16, R15 and R16 are independently selected from the group consisting of hydrogen, alkyl and â€”COR17, or R15 and R16 together with the nitrogen atom to which they are attached form an optionally substituted heterocycle, R17 is selected from the group consisting of hydrogen, alkyl, alkoxy and â€”NR18R19, R18 and R19 are independently selected from the group consisting of hydrogen or alkyl, or R18 and R19 together with the nitrogen atom to which they are attached form an optionally substituted heterocycle, R14 is hydrogen, alkyl and â€”COR20, R20 is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aralkyl, heterocycloalkyl and â€”NR21R22, in which the alkyl, aryl or heterocycloalkyl are unsubstituted or substituted by at least one member selected from the group consisting of alkyl, â€”OH, alkoxy, nitro, cyano, halogen, and â€”NR4R5; R21 and R22 are independently selected from the group consisting of hydrogen and alkyl, or R21 or R22 together with the nitrogen atom to which they are attached form an optionally substituted heterocycle, W is S, X is selected from the group consisting of â€”(CH2)nâ€”, â€”(CH2)nâ€”COâ€”, â€”N(R45)â€”COâ€”(CH2)nâ€”COâ€”, â€”N(R45)â€”COâ€”Dâ€”COâ€”, â€”COâ€”N(R45)â€”Dâ€”COâ€”, â€”COâ€”Dâ€”COâ€”, â€”CH&boxH;CHâ€”(CH2)nâ€”COâ€”, â€”N(R45)â€”(CH2)nâ€”COâ€”, â€”N(R45)â€”COâ€”Câ€”(R46R47)â€”COâ€”, â€”Oâ€”(CH2)nâ€”COâ€”, â€”N(R45)â€”COâ€”NHâ€”C(R46R47) â€”COâ€”,â€”COâ€”N(R45)â€”C(R46R47)â€”COâ€”, â€”Sâ€”(CH2)nâ€”COâ€” and â€”Zâ€”COâ€”; D is phenylene unsubstituted or substituted by at least one member of the group consisting of alkyl, alkoxy, â€”OH, nitro, halogen, cyano, and carboxyl optionally esterified by alkyl; Z is heterocycle, R45 is hydrogen or alkyl, R46 and R47 are independently selected from the group consisting of the group consisting of hydrogen, alkyl, aryl and aralkyl, the alkyl and aryl groups are unsubstituted or substituted by at least one member selected from the group consisting of â€”OH, â€”SH, halogen, nitro, alkyl, alkoxy, alkylthio, aralkoxy, aryl-alkylthio, â€”NR48R49 and carboxyl optionally esterified by alkyl; R48 and R49 are independently selected from the group consisting of hydrogen, alkyl, and â€”COR50, R48 and R49 together with the nitrogen atom to which they are attached form an optionally substituted heterocycle; R50 is hydrogen, alkyl, alkoxy and â€”NR51R52. R51 and R52 are independently hydrogen or alkyl, or R51 and R52 together with the nitrogen atom to which they are attached, form an optionally substituted heterocycle; n is an integer between 0 and 6; Y is â€”(CH2)pâ€”; P is O; Het is a heterocycle or a pharmaceutically acceptable addition salt with acids or bases thereof, with the exception of the compounds of formula (I) wherein Het is tetrahydrofuran or tetrahydropyran, R1 is OR3, R3 is selected from the group consisting of hydrogen, alkyl, arylalkyl, heterocycloalkylcarbonyl, the heterocycloalkyl being connected by a carbon atom, alkylcarbonyl, arylcarbonyl or aralkylcarbonyl, R2 is hydrogen and Y is â€”(CH2)pâ€” with p=0, the X is â€”COâ€”N(R45)â€”Câ€”(R46R47)â€”COâ€” with R45=R46=H and with the exclusion of the compound wherein i) X represents â€”CH2â€”C(O)â€” and Het 4-oxo-4H-1-benzopyran-2-yl; ii) X represents â€”NHâ€”C(O)â€”C(O)â€” and Het phenothiazin-1-yl; iii) X represents â€”CH2â€” and Het 1-azabicyclo[2.2.2] oct-3yl.