Fused heterocyclic compounds

A compound having serotonin receptor modulating activity of formula (II)

• wherein
• m is 0, 1 or 2;
• p is 1, 2 or 3, with the proviso that where m is 1 or 2, p is not 1;
• m+p is less than or equal to 4;
• q is 0 or 1;
• R3)r is H;
• Ar is an aryl or heteroaryl ring selected from the group consisting of:
• a) phenyl, optionally mono-, di- or tri-substituted with Rr or di-substituted on adjacent carbons with —OC1-4alkyleneO—, —(CH2)2-3NH—, —(CH2)1-2NH(CH2)—, —(CH2)2-3N(C1-4alkyl)- or —(CH2)1-2N(C1-4alkyl)(CH2)—;
• Rr is selected from the group consisting of —OH, —C1-6alkyl, —OC1-6alkyl, —C2-6alkenyl, —OC3-6alkenyl, —C2-6alkynyl, —OC3-6alkynyl, —CN, —NO2, —N(Ry)Rz (wherein Ry and Rz are independently selected from H or C1-6alkyl), —(C═O)N(Ry)Rz, —(N—Rt)CORt, —(N—Rt)SO2C1-6alkyl (wherein Rt is H or C1-6alkyl), —(C═O)C1-6alkyl, —(S═(O)n)—C1-6alkyl (wherein n is selected from 0, 1 or 2), —SO2N(Ry)Rz, —SCF3, halo, —CF3, —OCF3, —COOH and —COOC1-6alkyl;
• b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C1-4alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N═, the fused rings optionally mono- , di- or tri-substituted with Rr;
• c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N═, the fused rings optionally mono-, di- or tri-substituted with Rr;
• d) naphthyl, optionally mono- , di- or tri-substituted with Rr;
• e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C1-4alkyl), having up to one additional carbon atoms optionally replaced by —N═, optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rr;
• and
• f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N═, optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Rr;
• g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono- , di- or tri-substituted with Rr;
• ALK is a branched or unbranched C1-8alkylene, C2-8alkenylene, C2-8alkynylene or C3-8cycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of:
• —OH, —OC1-6alkyl, —OC3-6cycloalkyl, —CN, —NO2, —N(Ra)Rb (wherein Ra and Rb are independently selected from H, C1-6alkyl or C2-6alkenyl), —(C═O)N(Ra)Rb, —(N—Rc)CORc, —(N—Rc)SO2C1-6alkyl (wherein Rc is H or C1-6alkyl), —(C═O)C1-6alkyl, —(S═(O)d)—C1-6alkyl (wherein d is selected from 0, 1 or 2), —SO2N(Ra)Rb, —SCF3, halo, —CF3, —OCF3, —COOH and —COOC1-6alkyl;
• CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of:
• i) phenyl, optionally mono-, di- or tri-substituted with Rq or di-substituted on adjacent carbons with —OC1-4alkyleneO—, —(CH2)2-3NH—, —(CH2)1-2NH(CH2)—, —(CH2)2-3N(C1-4alkyl)- or —(CH2)1-2N(C1-4alkyl)(CH2)—;
• Rq is selected from the group consisting of —OH, —C1-6alkyl, —OC1-6alkyl, —C3-6cycloalkyl, —OC3-6cycloalkyl, phenyl, —Ophenyl, benzyl, —Obenzyl, —CN, —NO2, —N(Ra)Rb (wherein Ra and Rb are independently selected from H, C1-6alkyl or C2-6alkenyl, or Ra and Rb may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, ═N—, >NH or >N(C1-4alkyl), optionally having one carbon substituted with —OH, and optionally having one or two unsaturated bonds in the ring), —(C═O)N(Ra)Rb, —(N—Rc)CORc, —(N—Rc)SO2C1-6alkyl (wherein Rc is H or C1-6alkyl or two Rc in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), —N—(SO2C1-6alkyl)2, —(C═O)C1-6alkyl, —(S═(O)d)—C1-6alkyl (wherein d is selected from 0, 1 or 2), —SO2N(Ra)Rb, —SCF3, halo, —CF3, —OCF3, —COOH and —COOC1-6alkyl;
• ii) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C1-4alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N═, the fused rings optionally mono-, di- or tri-substituted with Rq;
• iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N═, the fused rings optionally mono-, di- or tri-substituted with Rq;
• iv) naphthyl, optionally mono-, di- or tri-substituted with Rq;
• v) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C1-4alkyl), having up to one additional carbon atoms optionally replaced by —N═, optionally mono- or di-substituted with Rq and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rq;
• vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N═, optionally mono- or di-substituted with Rq and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Rq;
• vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, —N═, >NH or >NRq, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents Rq and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents Rq;
• and
• viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, —N═, >NH or >NRq, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from O, S, —N═, >NH or >NRq, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents Rq;
• R1 is selected from the group consisting of H, C1-7alkyl, C2-7alkenyl, C2-7alkynyl, C3-7cycloalkyl, C3-7cycloalkylC1-7alkyl, C3-7cycloalkenyl, C3-7cycloalkenylC1-7alkyl and benzo-fusedC4-7cycloalkyl, each optionally mono-, di-, or tri-substituted with Rp;
• Rp is selected from the group consisting of —OH, —OC1-6alkyl, —C3-6cycloalkyl, —OC3-6cycloalkyl, —CN, —NO2, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, —N(Rs)Ru (wherein Rs and Ru are independently selected from H or C1-6alkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, ═N—, >NH or >N(C1-4alkyl) and optionally having one or two unsaturated bonds in the ring), —(C═O)N(Rs)Ru, —(N—Rv)CORv, —(N—Rv)SO2C1-6alkyl (wherein Rv is H or C1-6alkyl or two Rv in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), —(C═O)C1-6alkyl, —(S═(O)n)—C1-6alkyl (wherein n is selected from 0, 1 or 2), —SO2N(Rs)Ru, —SCF3, halo, —CF3, —OCF3, —COOH and —COOC1-6alkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of:
• —OH, —C1-6alkyl, —OC1-6alkyl, —CN, —NO2, —N(Ra)Rb (wherein Ra and Rb are independently selected from H, C1-6alkyl or C2-6alkenyl), —(C═O)N(Ra)Rb, —(N—Rc)CORc, —(N—Rc)SO2C1-6alkyl (wherein Rc is H or C1-6alkyl), —(C═O)C1-6alkyl, —(S═(O)d)—C1-6alkyl (wherein d is selected from 0, 1 or 2), —SO2N(Ra)Rb, —SCF3, halo, —CF3, —OCF3, —COOH and —COOC1-6alkyl;
• and enantiomers, diastereomers, and pharmaceutically acceptable salts, thereof.