Sulphonamido-substituted bridged bicycloalkyl derivatives

A compound of formula IIA:

• wherein:
• w is 1 or 2;
• and
• A2 represents —CH2—NR13—CXY—CH2— or
• R12 represents C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl;
• or two R12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1 ]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO2, C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl, OR11, NHR11, and COR11;
• R13 represents R9, —COR10, —CO2R10, —SO2R10, —CON(R9)2 or —SO2N(R9)2;
• Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF3, NO2, CN, OCF3, C1-6alkyl and C1-6alkoxy;
• “heterocyclyl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein none of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• and
• “heteroaryl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• or a pharmaceutically acceptable salt thereof.

A compound of formula III:

• wherein w is 1 or 2;
• Z completes an aromatic ring;
• R1 represents H, C1-4alkyl, or C2-4alkenyl;
• R2 represents H;
• R3 represents C1-16alkyl, C3-10cycloalkyl, C2-16alkenyl, C2-16alkynyl, C6-10arylC1-6alkyl, heteroarylC1-6alkyl, C6-10arylC2-6alkenyl, heteroarylC2-6alkenyl, C6-10aryl, bi(C6-10aryl), heteroaryl, bi(heteroaryl) or heterocyclyl;
• wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups represented by R3 or forming part of a group represented by R3 optionally bear up to 3 substituents independently selected from halogen, CN, NO2, —OR7, —SR7, —S(O)tR8 where t is 1 or 2, —N(R7)2, —COR7, —CO2R7, —OCOR8, —CON(R7)2, —NR7COR8, —C1-6alkylNR7COR8, —NR7CO2R8 and —NR7SO2R8;
• and the aryl, heteroaryl and heterocyclic groups representented by R3 or forming part of a group represented by R3 optionally bear up to 5 substituents independently selected from R8, halogen, CN, NO2, —OR7, —SR7, —S(O)tR8 where t is 1 or 2, —N(R7)2, —COR7, —CO2R7, —OCOR8, —CON(R7)2, —NR7COR8, —C1-6alkylNR7COR8, —NR7CO2R8 and —NR7SO2R8, wherein the R3 heteroaryl group is a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• R4, R5 and R6 independently represent R9, halogen, CN, NO2, —OR9, —SR9, —S(O)tR10 where t is 1 or 2, —N(R9)2, —COR9, —CO2R9, —OCOR10, —CON(R9)2, —SO2N(R9)2, —NR9COR10, —NR9CO2R10, —NR9SO2R10, —CH═CHCH2N(R16)2, —CH2OR10, —CH2N(R16)2, —NHCOCH2OR10 or —NHCOCH2N(R16)2;
• R7 represents H or R8;
• or two R7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
• R8 represents C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10alkenyl, C2-10alkynyl, Ar or —C1-6alkylAr;
• R9 represents H or R10;
• or two R9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R12, —COR12 or —SO2R12;
• R10 represents C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10alkenyl, C2-10alkynyl, C6-10aryl, heteroaryl, heterocyclyl, C6-10arylC1-6alkyl, heteroarylC1-6alkyl, C6-10arylC2-6alkenyl, or heteroarylC2-6alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF3, NO2, CN, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO2, CN, R12, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12, wherein the R10 heteroaryl group is selected from the group consisting of pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, 1,2,4-triazine, 1,3,5-triazine, 1,2,3,4-tetrahydroisoquinoline, imidazor[2,1-b]thiazole and benzo[1,4]dioxin;
• R11 represents H, C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl;
• R12 represents C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl;
• or two R12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO2, C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl, OR11, NHR11, and COR11;
• each R16 independently represents H or R10, or two R16 groups together with the nitrogen to which they are mutually attached complete a mono- or bicyclic heterocyclic ring system of 5-10 ring atoms selected from C, N, O and S, said ring system optionally having an additional aryl or heteroaryl ring fused thereto, said heterocyclic system and/or additional fused ring bearing 0-3 substituents independently selected from halogen, NO2, CN, R12, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF3, NO2, CN, OCF3, C1-6alkyl and C1-6alkoxy;
• “heterocyclyl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein none of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• and
• or a pharmaceutically acceptable salt thereof.

A compound of formula IIIC:

• wherein
• X represents halogen, R9, —OR9, —SR9, —S(O)tR10 where t is 1 or 2, —OSO2R9, —N(R9)2, —COR9, —CO2R9, —OCOR10, —OCO2R10, —CON(R9)2, —SO2N(R9)2, —OSO2N(R9)2, —NR9COR10, —NR9CO2R10 or —NR9SO2R10;
• Y represents H or C1-6alkyl;
• or X and Y together represent ═O, ═S, ═N—OR11 or ═CHR11;
• R1 represents H, C1-4alkyl, or C2-4alkenyl;
• R2 represents H;
• R3 represents C1-16alkyl, C3-10cycloalkyl, C2-16alkenyl, C2-16alkynyl, C6-10arylC1-6alkyl, heteroarylC1-6alkyl, C6-10arylC2-6alkenyl, heteroarylC2-6alkenyl, C6-10aryl, bi(C6-10aryl), heteroaryl, bi(heteroaryl) or heterocyclyl;
• wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups represented by R3 or forming part of a group represented by R3 optionally bear up to 3 substituents independently selected from halogen, CN, NO2, —OR7, —SR7, —S(O)tR8 where t is 1 or 2, —N(R7)2, —COR7, —CO2R7, —OCOR8, —CON(R7)2, —NR7COR8, —C1-6alkylNR7COR8, —NR7CO2R8 and —NR7SO2R8;
• and the aryl, heteroaryl and heterocyclic groups represented by R3 or forming part of a group represented by R3 optionally bear up to 5 substituents independently selected from R8, halogen, CN, NO2, —OR7, —SR7, —S(O)tR8 where t is 1 or 2, —N(R7)2, —COR7, —CO2R7, —OCOR8, —CON(R7)2, —NR7COR8, —C1-6alkylNR7COR8, —NR7CO2R8 and —NR7SO2R8, wherein the R3 heteroaryl group is a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
• R4 represents halogen, CN, NO2, —OR9, —SR9, —S(O)tR10 where t is 1 or 2, —N(R9)2, —COR9, —CO2R9, OCOR10, —CON(R9)2, —SO2N(R9)2, —NR9COR10, —NR9CO2R10, —NR9SO2R10, —CH═CHCH2N(R16)2, —CH2OR10, —CH2N(R16)2, —NHCOCH2OR10, or —NHCOCH2N(R16)2;
• R7 represents H or R8;
• or two R7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
• R8 represents C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10alkenyl, C2-10alkynyl, Ar or —C1-6alkylAr;
• R9 H or R10;
• or two R9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R12, —COR12 or —SO2R12;
• R10 represents C1-10alkyl, perfluoroC1-6alkyl, C3-10cycloalkyl, C3-6cycloalkylC1-6alkyl, C2-10alkenyl, C2-10alkynyl, C6-10aryl, heteroaryl, heterocyclyl, C6-10arylC1-6alkyl, heteroarylC1-6alkyl, C6-10arylC2-6alkenyl, or heteroarylC2-6alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF3, NO2, CN, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO2, CN, R12, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12, wherein the R10 heteroaryl group is selected from the group consisting of pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, 1,2,4-triazine, 1,3,5-triazine, 1,2,3,4-tetrahydroisoquinoline, imidazo[2,1-b]thiazole and benzo[1,4]dioxin;
• R11 represents H, C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl;
• R12 represents C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl;
• or two R12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO2, C1-6alkyl, perfluoroC1-6alkyl, C3-7cycloalkly, C2-6alkenyl, C2-6alkynyl, Ar, —C1-6alkylAr or ArOC1-6alkyl, OR11, NHR11, and COR11
• R13 represents R9, —COR10, —CO2R10, —SO2R10, —CON(R9)2 or —SO2N(R9)2;
• each R16 independently represents H or R10, or two R16 groups together with the nitrogen to which they are mutually attached complete a mono- or bicyclic heterocyclic ring system of 5-10 ring atoms selected from C, N, O and S, said ring system optionally having an additional aryl or heteroaryl ring fused thereto, said heterocyclic system and/or additional fused ring bearing 0-3 substituents independently selected from halogen, NO2, CN, R12, —OR11, —SR11, —SO2R12, —COR11, —CO2R11, —CON(R11)2, —OCOR12, —N(R11)2 and —NR11COR12;
• V represents CR4 or N;
• W represents CH or N;
• a is 0 or 1;
• b is 0;
• and
• w is 1 or 2;
• or a pharmaceutically acceptable salt thereof.