Polycyclic compounds

A method for treating a cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a polycyclic compound of formula [I],

• 11
• wherein;
• ring A is a nitrogen-containing 5 or 6 membered heteroaromatic ring which may be substituted by R1 and R2;
• R1 and R2 are independently hydrogen, halogen, (C1-C5) alkyl, hydroxy, mercapto, (C1-C5) alkoxy, (C4-C7) cycloalkyloxy, (C3-C7)cycloalkyl(C1-C5)alkyloxy, (C1-C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, amino, mono-(C1-C5)-alkylamino, di-(C1-C5)-alkylamino or —Y′-Z′-N(R6′) (R7′);
• wherein
• Y′ is O, S or N(R9′), wherein R9′ is hydrogen or (C1-C5) alkyl;
• or when Y′ is N(R9′), N(R9′) forms an aliphatic ring together with N(R6′) and Z′;
• Z′ is (C2-C5) alkylene;
• or Z′ forms an aliphatic ring together with N(R6′) and (NR9′);
• or Z′ forms an aliphatic ring together with N(R6′);
• R6′ and R7′ are independently hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C3-C7) cycloalkyl, (C4-C7) cycloalkyl, (C3-C7)cycloalkyl(C1-C5)alkyloxy or aryl(C1-C5)alkyl optionally substituted with one to three substituents selected form the group consisting of hydroxy, (C1-C5) alkoxy, amino, mono-(C1-C5)-alkylamino and di-(C1-C5)-alkylamino;
• or R6′ and R7′ form an aliphatic ring optionally containing one to three heteroatom(s) selected from oxygen, nitrogen and sulfur together with the adjacent nitrogen;
• or R6′ forms an aliphatic ring together with the adjacent nitrogen and Z′;
• or R6′ forms an aliphatic ring together with the adjacent nitrogen, N(R9′) and Z′;
• ring B is a benzene ring, naphthalene ring or benzene ring substituted with (C1-C5) alkylenedioxy group which is optionally substituted by R3, R4 and R5;
• R3, R4 and R5 are independently hydrogen, halogen, hydroxy, mercapto, (C1-C5) alkyl, (C1-C5) halogeno-alkyl, (C1-C5) alkoxy, (C1-C5) halogeno-alkoxy, (C3-C5) alkenyloxy, (C4-C7) cycloalkyloxy, (C3-C7)cycloalkyl(C1-C5) alkyloxy, aryl(C1-C5)alkyloxy, (C1-C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, amino, mono-(C1-C5)-alkylamino or di-(C1-C5)-alkylamino;
• X is O or N—O—R8 wherein R8 is a hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C4-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C5)alkyl, aryl, or aryl(C1-C5)alkyl;
• Y is O, S or N(R9) wherein R9 is hydrogen or (C1-C5) alkyl;
• or when Y is N(R9), N(R9) forms an aliphatic ring together with N(R6) and Z;
• Z is (C2-C5) alkylene optionally substituted with (C1-C5) alkyl radical(s);
• or Z forms an aliphatic ring together with N(R6) and N(R9);
• or Z forms an aliphatic ring together with N(R6);
• and
• R6 and R7 are independently hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C4-C7) cycloalkyl, (C3-C7)cycloalkyl(C1-C5)alkyl or aryl(C1-C5)alkyl optionally substituted with hydroxy, alkoxy, amino, mono-(C1-C5)-alkylamino or di-(C1-C5)-alkylamino;
• or R6 and R7 form an aliphatic ring optionally containing one to three heteroatom(s) selected from the group consisting of oxygen, nitrogen and sulfur together with the adjacent nitrogen;
• or R6 forms an aliphatic ring together with the adjacent nitrogen and Z;
• or R6 forms an aliphatic ring together with the adjacent nitrogen, N(R9) and Z.

A process for producing polycyclic compounds of formula [I],

• 12
• wherein ring A is a nitrogen-containing 5 or 6 membered heteroaromatic ring which may be substituted by R1 and R2;
• R1 and R2 are independently hydrogen, halogen, (C1-C5) alkyl, hydroxy, mercapto, (C1-C5) alkoxy, (C4-C7) cycloalkyloxy, (C3-C7)cycloalkyl(C1-C5)alkyloxy, (C1-C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, amino, mono-(C1-C5)-alkylamino, di-(C1-C5)-alkylamino or —Y′-Z′-N(R6′) (R7′);
• wherein
• Y′ is O, S or N(R9′), wherein R9′ is hydrogen or (C1-C5) alkyl;
• or when Y′ is N(R9′), N(R9′) forms an aliphatic ring together with N(R6′) and Z′;
• Z′ is (C2-C5) alkylene;
• or Z′ forms an aliphatic ring together with N(R6′) and (NR9′);
• or Z′ forms an aliphatic ring together with N(R6′);
• R6′ and R7′ are independently hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C3-C7) cycloalkyl, (C4-C7) cycloalkyl, (C3-C7)cycloalkyl(C1-C5)alkyl or aryl(C1-C5)alkyl optionally substituted with one to three substituents selected form the group consisting of hydroxy, (C1-C5) alkoxy, amino, mono-(C1-C5)-alkylamino and di-(C1-C5)-alkylamino;
• or R6′ and R7′ form an aliphatic ring optionally containing one to three heteroatom(s) selected from oxygen, nitrogen and sulfur together with the adjacent nitrogen;
• or R6′ forms an aliphatic ring together with the adjacent nitrogen and Z′;
• or R6′ forms an aliphatic ring together with the adjacent nitrogen, N(R9′) and Z′;
• ring B is a benzene ring, naphthalene ring or benzene ring substituted with (C1-C5) alkylenedioxy group which is optionally substituted by R3, R4 and R5;
• R3, R4 and R5 are independently hydrogen, halogen, hydroxy, mercapto, (C1-C5) alkyl, (C1-C5) halogeno-alkyl, (C1-C5) alkoxy, (C1-C5) halogeno-alkoxy, (C3-C5) alkenyloxy, (C4-C7) cycloalkyloxy, (C3-C7)cycloalkyl(C1-C5) alkyloxy, aryl(C1-C5)alkyloxy, (C1-C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, amino, mono-(C1-C5)-alkylamino or di-(C1-C5)-alkylamino;
• X is O;
• Y is O, S or N(R9) wherein R9 is hydrogen or (C1-C5) alkyl;
• or when Y is N(R9), N(R9) forms an aliphatic ring together with N(R6) and Z;
• Z is (C2-C5) alkylene optionally substituted with (C1-C5) alkyl radical(s);
• or Z forms an aliphatic ring together with N(R6) and N(R9);
• or Z forms an aliphatic ring together with N(R6);
• and
• R6 and R7 are independently hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C4-C7) cycloalkyl, (C3-C7)cycloalkyl(C1-C5)alkyl or aryl(C1-C5)alkyl optionally substituted with hydroxy, alkoxy, amino, mono-(C1-C5)-alkylamino or di-(C1-C5)-alkylamino;
• or R6 and R7 form an aliphatic ring optionally containing one to three heteroatom(s) selected from the group consisting of oxygen, nitrogen and sulfur together with the adjacent nitrogen;
• or R6 forms an aliphatic ring together with the adjacent nitrogen and Z;
• or R6 forms an aliphatic ring together with the adjacent nitrogen, N(R9) and Z,
• which comprises reacting a compound of the formula [VI],
• 13
• wherein ring A, ring B, R1, R2, R3, R4 and R5 are the same as defined above;
• Hal is halogen;
• with a compound of the formula [VIII],
• 14
• wherein R6, R7, Y and Z are the same as defined above.

A process for producing polycyclic compounds of formula [I],

• 15
• wherein ring A is a nitrogen-containing 5 or 6 membered heteroaromatic ring which may be substituted by R1 and R2;
• R1 and R2 are independently hydrogen, halogen, (C1-C5) alkyl, hydroxy, mercapto, (C1-C5) alkoxy, (C4-C7) cycloalkyloxy, (C3-C7)cycloalkyl(C1-C5)alkyloxy, (C1-C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, amino, mono-(C1-C5)-alkylamino, di-(C1-C5)-alkylamino or —Y′-Z′-N(R6′)(R7′);
• wherein
• Y′ is O, S or N(R9′), wherein R9′ is hydrogen or (C1-C5) alkyl;
• or when Y′ is N(R9′), N(R9′) forms an aliphatic ring together with N(R6′) and Z′;
• Z′ is (C2-C5) alkylene;
• or Z′ forms an aliphatic ring together with N(R6′) and (NR9′);
• or Z′ forms an aliphatic ring together with N(R6′);
• R6′ and R7′ are independently hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C4-C7) cycloalkyl, (C3-C7)cycloalkyl(C1-C5)alkyl or aryl(C1-C5)alkyl optionally substituted with one to three substituents selected from the group consisting of hydroxy, (C1-C5) alkoxy, amino, mono-(C1-C5)-alkylamino and di-(C1-C5)-alkylamino;
• or R6′ and R7, form an aliphatic ring optionally containing one to three heteroatom(s) selected from the group consisting of oxygen, nitrogen and sulfur together with the adjacent nitrogen;
• or R6′ forms an aliphatic ring together with the adjacent nitrogen and Z′;
• or R6′ forms an aliphatic ring together with the adjacent nitrogen, N(R9′) and Z′;
• ring B is a benzene ring, naphthalene ring or benzene ring substituted with (C1-C5) alkylenedioxy group which is optionally substituted by R3, R4 and R5;
• R3, R4 and R5 are independently hydrogen, halogen, hydroxy, mercapto, (C1-C5) alkyl, (C1-C5) halogeno-alkyl, (C1-C5) alkoxy, (C1-C5) halogeno-alkoxy, (C3-C5) alkenyloxy, (C4-C7) cycloalkyloxy, (C3-C7)cycloalkyl(C1-C5)alkyloxy, aryl(C1-C5)alkyloxy, (C1-C5) alkylthio, (C1-C5) alkylsulfinyl, (C1-C5) alkylsulfonyl, amino, mono-(C1-C5)-alkylamino or di-(C1-C5)-alkylamino;
• X is O;
• Y is O, S or N(R9) wherein R9 is hydrogen or (C1-C5) alkyl;
• or when Y is N(R9), N(R9) forms an aliphatic ring together with N(R6) and Z;
• Z is (C2-C5) alkylene optionally substituted with (C1-C5) alkyl radical(s);
• or Z forms an aliphatic ring together with N(R6) and N(R9);
• or Z forms an aliphatic ring together with N(R6);
• and
• R6 and R7 are independently hydrogen, (C1-C5) alkyl, (C3-C5) alkenyl, (C4-C7) cycloalkyl, (C3-C7)cycloalkyl, (C1-C5) alkyl or aryl, (C1-C5)alkyl optionally substituted with hydroxy, alkoxy, amino, mono-(C1-C5)-alkylamino or di-(C1-C5)-alkylamino;
• or R6 and R7 form an aliphatic ring optionally containing one to three heteroatom(s) selected from the group consisting of oxygen, nitrogen and sulfur together with the adjacent nitrogen;
• or R6 forms an aliphatic ring together with the adjacent nitrogen and Z;
• or R6 forms an aliphatic ring together with the adjacent nitrogen, N(R9) and Z,
• which comprises reacting a compound of formula [VII],
• 16
• wherein ring A, ring B, R1, R R3, R4 and R5 are the same as defined above;
• and R12 is (C1-C5) alkyl, (C1-C5) halogenoalkyl or aryl,
• with a compound of formula [VIII],
• 17
• wherein R6, R7, Y and Z are the same as defined above.