Patent ID: 6740655
Filing Date: 2004-05-25
Classification: A61K,A61P,C07D

Abstract:
A compound of Formula (1.0.0): or a pharmaceutically acceptable salt thereof;wherein -jis 0 or 1;-kis 0 or 1;-mis 0 or 1;-nis 1 or 2;-Wis â€”Oâ€”; or  â€”S(&boxH;O)tâ€”, where t is 0, 1, or 2;whereR3 is â€”H; â€”(C1-C3) alkyl; â€”OR12; phenyl; or benzyl; RA and RB are each a member independently selected from the group consisting of â€”H; â€”F; â€”CF3; â€”(C1-C4) alkyl; â€”(C3-C7) cycloalkyl; phenyl; or benzyl; wherein said alkyl, cycloalkyl, phenyl, or benzyl moiety is each independently substituted with 0 to 3 substituents R10; provided thatfor the above and all other applicable meanings of RA and RB, when R10 as a substituent of RA or RB has the meaning of â€”OR12, â€”OC(&boxH;O)R12, or â€”OC(&boxH;O)NR12R13, the positional relationship of said â€”OR12, â€”OC(&boxH;O)R12, or â€”OC(&boxH;O)NR12R13 to â€”OR12 as a meaning of E, is other than a vicinal one; whereR10 is a member selected from the group consisting of â€”F; â€”Cl; â€”CF3; â€”CN; â€”OR12; (C1-C2) alkyl; hydroxy(C1-C2) alkyl; â€”Oâ€”C(&boxH;O)R13; â€”Oâ€”C(&boxH;O)NR12R13; â€”NR12R13; â€”NR12C(&boxH;O)R13; â€”NR12C(&boxH;O)OR13; â€”NR12C(&boxH;O)2R13; and â€”S(&boxH;O)2NR12R13; whereR12 and R13 are each a member independently selected from the group consisting of â€”H; â€”(C1-C4) alkyl; phenyl; or benzyl; wherein said alkyl, phenyl, or benzyl is substituted by 0 to 3 substituents selected from the group consisting of F and Cl; orRA and RB are taken together, provided that m is 1, to form a spiro moiety of Formula (1.1.0): wherer and s are independently 0 to 4 provided that the sum of r+s is at least 1 but not greater than 5; andQA is selected from the group consisting of â€”CH2â€”, â€”CHF, â€”CF2, â€”N(R3)â€”, â€”Oâ€”; and â€”S(&boxH;O)tâ€”, where t is 0, 1, or 2; and said spiro moiety is substituted as to any one or A more carbon atoms thereof, including the carbon atom of the group â€”CH2â€” defining QA, by 0 to 3 substituents R10, where R3 and R10 have the same meanings as defined above; provided thatfor the above and all other applicable meanings of RA and RB, when R10 as a substituent of RA or RB has the meaning of â€”OR12, â€”OC(&boxH;O)R12, or â€”OC(&boxH;O)NR12R13, the positional relationship of said â€”OR12, â€”OC(&boxH;O)R12, or â€”OC(&boxH;O)NR12R13 to â€”OR12 as a meaning of E, is other than a vicinal one; RC and RD have the same meaning as defined above for RA and RB, except that at least one of RC and RD must be â€”H, and they are selected independently of each other and of RA and RB; AA is a member independently selected from the group consisting of the following(a) a saturated or unsaturated cyclic or bicyclic (C3-C9) heterocyclic group which is a member selected from the group consisting of furanyl; thienyl; pyrrolyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrazolyl; oxadiazolyl; thiadiazolyl; imidazolyl; pyrazinyl; pyrimidinyl; pyridazinyl; triazolyl; tetrazolyl; 2,3-benzofuranyl; 2,3-dihydrobenzo-furanyl; 1,3-dihydroiso-benzofuranyl; benzo[b]thienyl; indolyl; indolinyl; isoindolinyl; 2H-1-benzopyranyl; 4H-1-benzopyranyl; 1H-2-benzopyranyl; chromanyl; isochromanyl; quinolinyl; isoquinolinyl; 1,2,3,4-tetrahydro-quinolinyl; 1,2,3,4-tetrahydro-isoquinolinyl; 1,3-benzodioxolyl; 3H-2, 1-benzoxathiolyl; benzoxazolyl; 1,2-benzisoxazolyl; 2,1-benzisoxazolyl; 1,2-benzodithiolyl; 1,3-benzodithiolyl; benzothiazolyl; 1,2-benzisothiazolyl; benzimidazolyl; indazolyl; 1,4-benzodioxanyl; 4H-3,1-benzoxazinyl; 2H-1,4-benzoxazinyl; 1,4-benzothiazinyl; 1,2-benzothiazinyl; quinazolinyl; quinoxalinyl; phthalazinyl; cinnolinyl; 1,2,3-benzothiadiazolyl; 2H-1,2,4-benzo-thiadiazinyl; 2H-1,2,4-benzo-oxadiazinyl; benzoxtriazinyl; 1,2,3-benzotriazinyl; 1,2,4-benzotriazinyl; and benzotetrazinyl; wherein said heterocyclic group is substituted as to any one or more nitrogen atoms thereof by 0 or 1 R9 substitutent, whereR9 is independently selected from the group consisting of â€”H; and â€”(C1-C4) alkyl; further wherein said heterocyclic group is substituted as to any one or more carbon atoms thereof by 0-3 R16 substitutents, whereR16 is independently selected from the group consisting of â€”F; â€”Cl; â€”CN; â€”OR12; (C1-C4) alkyl; (C3-C7) cycloalkyl; â€”CF3; â€”C(&boxH;O)OR12; â€”NO2; â€”NR12R13; hydroxy(C1-C4) alkylamino; phenyl; and benzyl; where R12 and R13 have the same meaning as defined above; and where said alkyl, alkoxy or cycloalkyl is each independently substituted by 0-3 R18 substituents, whereR18 is independently selected from the group consisting of â€”F; â€”Cl; â€”CN; â€”OR12; â€”CF3; â€”NR12R13 and phenyl; where R12 and R13 have the same meanings as defined above; and further ZA (b) is (C3-C7) cycloalkyl independently substituted by 0-3 R16 substituents where R16 has the same meaning as defined above; and still further ZA (c) is phenyl or pyridyl substituted by 0 to 3 substituents R4, whereR4 is a member independently selected from the group consisting of the following(1) â€”F; â€”Cl; â€”CN; â€”OR12; â€”S(&boxH;O)pR12; â€”C(&boxH;O)OR12; â€”OC(&boxH;O)R12; â€”NO2; â€”C(&boxH;O)NR12R13; â€”OC(&boxH;O)NR12R13; â€”NR12R13; â€”NR14C(&boxH;O)R12; â€”NR14C(O)OR12; â€”NR14S(&boxH;O)pR12; and â€”S(&boxH;O)pNR12R13; where p is 0, 1, or 2; and R12 and R13 have the same meaning as defined above; whereR14 is selected from the group consisting of â€”H; â€”CH3; and â€”CH2CH3; and further R4 (2) is independently â€”(C1-C4) alkyl; or â€”(C1-C4) alkoxy where R12 of â€”OR12 in the above definition of R4 has the meaning of â€”(C1-C4) alkyl; wherein said alkyl or alkoxy are each independently substituted with 0 to 3 substituents â€”F or â€”Cl; or 0 or 1 substituent (C1-C2) alkoxycarbonyl-; (C1-C2) alkylcarbonyl-; or (C1-C2) alkylcarbonyloxy-; and still further R4 (3) is independently phenyl; benzyl; or a heterocyclyl moiety selected from the group consisting of furanyl; tetrahydrofuranyl; oxetanyl; thienyl; tetrahydrothienyl; pyrrolyl; pyrrolidinyl; oxazolyl; oxazolidinyl; isoxazolyl; isoxazolidinyl; thiazolyl; thiazolidinyl; isothiazolyl; isothiazolidinyl; pyrazolyl; pyrazolidinyl; oxadiazolyl; thiadiazolyl; imidazolyl; imidazolidinyl; pyridinyl; pyrazinyl; pyrimidinyl; pyridazinyl; piperidinyl; piperazinyl; triazolyl; triazinyl; tetrazolyl; pyranyl; azetidinyl; morpholinyl, parathiazinyl; indolyl; indolinyl; benzo[b]furanyl; 2,3-dihydrobenzofuranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1-H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzthiazolyl; quinolinyl; isoquinolinyl; phthalazinyl; quinazolinyl; quinoxalinyl; and purinyl; wherein said phenyl, benzyl, or heterocyclyl moiety is each independently substituted with 0 to 2 substituents R10 where R10 has the same meaning as defined above; oron adjacent carbon atoms, where ZA is selected as phenyl, are taken together with the carbon atoms to which they are attached and the phenyl ring of which they are a part, to form a benzofused heterocyclyl moiety comprising a member selected from the group consisting of 2,3-benzofuranyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; benzo[b]thienyl; indolyl; indolinyl; isoindolinyl; 2H-1-benzopyranyl; 4H-1-benzopyranyl; 1H-benzopyranyl; chromanyl; isochromanyl; quinolinyl; isoquinolinyl; 1,2,3,4-tetrahydroquinolinyl; 1,2,3,4-tetrahydroisoquinolinyl; 1,3-benzodioxolyl; 3H-2,1-benzoxathiolyl; benzoxazolyl; 1,2-benzisoxazolyl; 2,1-benzisoxazolyl; 1,2-benzodithiolyl; 1,3-benzodithiolyl; benzothiazolyl; 1,2-benzisothiazolyl; benzimidazolyl; indazolyl; 1,4-benzodioxanyl; 4H-3,1-benzoxazinyl; 2H-1,4-benzoxazinyl; 1,4-benzothiazinyl; 1,2-benzothiazinyl; quinazolinyl; quinoxalinyl; phthalazinyl; cinnolinyl; 1,2,3-benzothiadiazolyl; 2H-1,2,4-benzothiadiazinyl; 2H-1,2,4-benzoxadiazinyl; benzoxtriazinyl; 1,2,3-benzotriazinyl; 1,2,4-benzotriazinyl; and benzotetrazinyl; ZB is phenyl; pyridyl; pyrimidinyl; imidazolyl; oxazolyl; furanyl; thienyl; thiazolyl; indonin-2-onyl; pyrazinyl; cyclopentyl; cyclohexyl; cyclopentenyl, cyclohexenyl, norbornanyl, norbornenyl, bicyclo[2.2.2]octanyl, bicyclo[3.2.1]octanyl, bicyclo[3.3.0]octanyl, bicyclo[2.2.2]oct-5-enyl, bicyclo[2.2.2]oct-7-enyl, bicyclo[3.3.1]nonanyl, or adamantanyl; R1 and R2 are each a member independently selected from the group consisting of â€”H; â€”F; â€”Cl; â€”OR12; â€”S(&boxH;O)pR12; â€”C(&boxH;O)OR12; â€”OC(&boxH;O)R12; â€”CN; â€”NO2; â€”C(&boxH;O)NR12R13; â€”NR12R13; and â€”S(&boxH;O)pNR12R13; where p is 0, 1, or 2; and R12 and R13 have the same meanings as defined above; E is selected from the group consisting of â€”H; â€”F; â€”Cl; â€”CN; â€”OR12; (C1-C4) alkyl; hydroxy(C1-C4) alkyl; â€”CF3; â€”NO2; â€”NR12R13; â€”NR12S(&boxH;O)2R13; and â€”S(&boxH;O)2NR12R13; where R12 and R13 have the same meanings as defined above; andR7 and R8 are each independently selected from the group consisting of â€”H; â€”F; â€”Cl; â€”OR12; (C1-C4) alkyl; hydroxy(C1-C4) alkyl; â€”CF3; â€”C(&boxH;O)OR12; â€”NR12R13; hydroxy(C1-C4) alkylamino; phenyl; benzyl; or a heterocyclyl moiety selected from the group consisting of pyrrolyl; oxazolyl; thiazolyl; oxadiazolyl; thiadiazolyl; imidazolyl; pyridinyl; tetrazolyl; indolyl; and benzimidazolyl; wherein said phenyl, benzyl, or heterocyclyl moiety is each independently substituted with 0 to 2 substituents R10 where R10 has the same meaning as defined above; in the event thatj or k is 1, or both j and k are 1 at the same time, a compound of Formula (1.0.0) is in the form of a N-oxide.