Pharmaceutical Compounds

A method for the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase, which method comprises administering to a subject in need thereof a compound of the formula (I):

• or a salt, tautomer, N-oxide or solvate thereof;
• wherein
• A is a bond, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;
• Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;
• Q is S or CR2;
• J is S or CH;
• provided that one of Q and J is S, and the other of Q and J is not S;
• when Q is S, there is a double bond between the ring carbon atoms “a” and “b” and a double bond between the ring nitrogen N and J;
• and when J is S, there is a double bond between Q and the ring carbon atom “a” and a double bond between the ring nitrogen N and the ring carbon atom “b”;
• R1 is hydrogen;
• a carbocyclic or heterocyclic group having from 3 to 12 ring members;
• or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2;
• R2 is hydrogen;
• halogen;
• C1-4 alkoxy;
• or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy;
• R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members;
• and
• R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy.

A compound of the formula (Ia):

• and salts, tautomers, N-oxides and solvates thereof;
• wherein
• A is a bond, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;
• Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;
• Q is S or CR2;
• J is S or CH;
• provided that one of Q and J is S, and the other of Q and J is not S;
• when Q is S, there is a double bond between the ring carbon atoms “a” and “b” and a double bond between the ring nitrogen N and J;
• and when J is S, there is a double bond between Q and the ring carbon atom “a” and a double bond between the ring nitrogen N and the ring carbon atom “b”;
• R1 is (i) a carbocyclic or heterocyclic group having from 3 to 12 ring members;
• or (ii) a C1-4 hydrocarbyl group substituted by a carbocyclic or heterocyclic group having from 3 to 12 ring members, the hydrocarbyl group being optionally further substituted by one or more substituents selected from halogen, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO and SO2;
• R2 is hydrogen;
• halogen;
• C1-4 alkoxy;
• or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxy or C1-4 alkoxy;
• R3 is selected from carbocyclic and heterocyclic groups having from 3 to 12 ring members;
• and
• R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxy or C1-4 alkoxy;
• but excluding:
• (A) the compound wherein the ring containing the moiety Q-J is a thiazole ring, A is a bond, R4 is hydrogen, R1 is cyclohexyl, Y is a bond and R3 is a methoxy-substituted dibenzofuran group;
• and
• (B) a compound wherein the ring containing the moiety Q-J is a thiazole ring, A is a bond, R4 is hydrogen and R1 is 4-pyridylmethyl or 5-quinolinyl, and Y—R3 is selected from 3,4-dichlorophenyl, 4-phenoxyphenyl, 4-biphenyl, 4-cyclohexylphenyl and 3-isoquinolinyl.

A composition comprising a pharmaceutically acceptable carrier and a compound of the formula (Ia):

• or a salt, tautomer, N-oxide or solvate thereof;
• wherein
• A is a bond, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;
• Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;
• Q is S or CR2;
• J is S or CH;
• provided that one of Q and J is S, and the other of Q and J is not S;
• when Q is S, there is a double bond between the ring carbon atoms “a” and “b” and a double bond between the ring nitrogen N and J;
• and when J is S, there is a double bond between Q and the ring carbon atom “a” and a double bond between the ring nitrogen N and the ring carbon atom “b”;
• R1 is (i) a carbocyclic or heterocyclic group having from 3 to 12 ring members;
• or (ii) a C1-4 hydrocarbyl group substituted by a carbocyclic or heterocyclic group having from 3 to 12 ring members, the hydrocarbyl group being optionally further substituted by one or more substituents selected from halogen, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO and SO2;
• R2 is hydrogen;
• halogen;
• C1-4 alkoxy;
• or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxy or C1-4 alkoxy;
• R3 is selected from carbocyclic and heterocyclic groups having from 3 to 12 ring members;
• and
• R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxy or C1-4 alkoxy;
• but excluding:
• (A) the compound wherein the ring containing the moiety Q-J is a thiazole ring, A is a bond, R4 is hydrogen, R1 is cyclohexyl, Y is a bond and R3 is a methoxy-substituted dibenzofuran group;
• and
• (B) a compound wherein the ring containing the moiety Q-J is a thiazole ring, A is a bond, R4 is hydrogen and R1 is 4-pyridylmethyl or 5-quinolinyl, and Y—R3 is selected from 3,4-dichlorophenyl, 4-phenoxyphenyl, 4-biphenyl, 4-cyclohexylphenyl and 3-isoquinolinyl.

A method for treating a disease or condition comprising or arising from abnormal cell growth in a mammal, which method comprises administering to the mammal, in an amount effective in inhibiting abnormal cell growth, a compound of the formula (I):

• or a salt, tautomer, N-oxide or solvate thereof;
• wherein
• A is a bond, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;
• Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;
• Q is S or CR2;
• J is S or CH;
• provided that one of Q and J is S, and the other of Q and J is not S;
• when Q is S, there is a double bond between the ring carbon atoms “a” and “b” and a double bond between the ring nitrogen N and J;
• and when J is S, there is a double bond between Q and the ring carbon atom “a” and a double bond between the ring nitrogen N and the ring carbon atom “b”;
• R1 is hydrogen;
• a carbocyclic or heterocyclic group having from 3 to 12 ring members;
• or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2;
• R2 is hydrogen;
• halogen;
• C1-4 alkoxy;
• or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy;
• R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members;
• and
• R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy.

A method for the diagnosis and treatment of a disease state or condition mediated by a cyclin dependent kinase, which method comprises (i) screening a patient to determine whether a disease or condition from which the patient is or may be suffering is one which would be susceptible to treatment with a compound having activity against cyclin dependent kinases;

• and (ii) where it is indicated that the disease or condition from which the patient is thus susceptible, thereafter administering to the patient a compound of the formula (I):
• or a salt, tautomer, N-oxide or solvate thereof;
• wherein
• A is a bond, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy;
• Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length;
• Q is S or CR2;
• J is S or CH;
• provided that one of Q and J is S, and the other of Q and J is not S;
• when Q is S, there is a double bond between the ring carbon atoms “a” and “b” and a double bond between the ring nitrogen N and J;
• and when J is S, there is a double bond between Q and the ring carbon atom “a” and a double bond between the ring nitrogen N and the ring carbon atom “b”;
• R1 is hydrogen;
• a carbocyclic or heterocyclic group having from 3 to 12 ring members;
• or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2;
• R2 is hydrogen;
• halogen;
• C1-4 alkoxy;
• or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy;
• R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members;
• and
• R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy.