Patent ID: 6559168
Filing Date: 2003-05-06
Classification: A61P,C07D

Abstract:
A compound of Formula (1.0.0): g is 0 or 1; j is 0 or 1; provided that when j is 0, n must be 2; k is 0 or 1; m is 0, 1, 2, or 3; n is 1 or 2; W1 is â€”Oâ€”; or â€”S(&boxH;O)tâ€”, where t is 0, 1, or 2; or â€”N(R3)â€” where R3 has the same meaning as defined below; W2 is â€”Oâ€”; S(&boxH;O)tâ€”, where t is 0, 1, or 2; â€”N(R3)â€” where R3 has the same meaning as defined below, or â€”CR29R30â€”; where R29 and R30 are each a member independently selected from the group consisting of â€”H; â€”F; â€”CF3; â€”(C1-C3)alkyl; â€”(C3-C6)cycloalkyl; phenyl; benzyl; and pyridyl; wherein said alkyl, cycloalkyl, phenyl, benzyl, and pyridyl moieties are each independently substituted with 0 to 3 substituents R10, where R10 has the same meaning as defined below; Y is â€”S(&boxH;O)tâ€”, where t is 0, 1, or 2; where R1a is a member selected from the group consisting of â€”H; â€”F; â€”Cl; â€”CN; â€”NO2; â€”(C1-C4)alkyl; â€”(C2-C4)alkynyl; fluorinated-(C1-C3)alkyl; fluorinated-(C1-C3)alkoxy; â€”OR16; and â€”C(&boxH;O)NR22aR22b; where R22a and R22b are each independently â€”H; CH3; â€”CH2CH3; â€”CH2CH2CH3; CH(CH3)2; â€”CH2CH2CH2CH3; â€”CH(CH3)CH2CH3; â€”CH2CH(CH3)2; â€”C(CH3)3; cyclopropyl; cyclobutyl; or cyclopentyl; 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; and benzyl; wherein said cycloalkyl, phenyl, and benzyl moieties are each independently substituted with 0 to 3 substituents R10; where R10 is a member selectedfrom the group consisting of phenyl; pyridyl; â€”F; â€”Cl; â€”CF3; oxo(&boxH;O); â€”OR16; â€”NO2; â€”CN; â€”C(&boxH;O)OR16; â€”Oâ€”C(&boxH;O)R16; â€”C(&boxH;O)NR16R17; â€”Oâ€”C(&boxH;O)NR16R17; â€”NR16R17; â€”NR16C(&boxH;O)R17; â€”NR16C(&boxH;O)OR17; â€”NR16S(&boxH;O)2R17; and â€”S(&boxH;O)2NR16R17; where said phenyl or pyridyl is substituted by 0 to 3 R11; where R11 is â€”F; â€”Cl; â€”CF3; â€”CN; â€”NO2; â€”OH; â€”(C1-C3)alkoxy; â€”(C1-C3)alkyl; or â€”NR16R17; and R16 and R17 are each a member independently selected from the group consisting of â€”H; â€”(C1-C4)alkyl; â€”(C2-C4)alkenyl; â€”(C3-C6)cycloalkyl; phenyl; benzyl; and pyridyl; wherein said alkyl, alkenyl, cycloalkyl, phenyl, benzyl, or pyridyl is substituted by 0 to 3 substituents selected from the group consisting of â€”F, â€”Cl, â€”CF3, â€”CN, and (C1-C3)alkyl; or RA and RB are taken together, but only in the case where m is 1, to form a spiro moiety of.Formula (1.2.0): wherer and s are independently 0 to 4 provided that the sum of r+s is at least 1 but not greater than 5; and XA is selected from â€”CH2â€”, â€”CH(R11)â€”, or C(R11)2â€”, where each R11 is selected independently of the other and each has the same meaning as defined above; â€”NR5â€”, where R15 has the same meaning as defined below; â€”Oâ€”; and â€”S(&boxH;O)tâ€”, where t is 0, 1, or 2; and said spiro moiety of partial Formula (1.2.0) is substituted as to any one or more carbon atoms thereof, other than that defining XA, by 0 to 3 substituents R14, where R14 has the same meaning as defined below; as to a nitrogen atom thereof by 0 or 1 substituent R15, where R15 has the same meaning as defined below; and as to a sulfur atom thereof by 0 or 2 oxygen atoms; RC and RD have the same meaning as defined above for RA and RB except that one of them must be â€”H, and they are selected independently of each other and of RA and RB; R1 and R2 may individually or together appear on any ring or rings within the meaning of the moiety G2 as defined below; and R1 and R2 are each a member independently selected from the-group consisting of â€”H; â€”F; â€”Cl; â€”CN; â€”NO2; â€”(C1-C4)alkyl; â€”(C2-C4)alkynyl; fluorinated â€”(C1-C3)alkyl; â€”OR6; and â€”C(&boxH;O)NR22aR22b; where R16, R22a, and R22b have the same meanings as defined above; R3 is â€”H; â€”(C1-C3)alkyl; phenyl; benzyl; or â€”OR16, where R16 has the same meaning as defined above; R4, R5 and R6 may individually or together appear on any ring or rings within the meaning of the moiety G1 as defined below; and R4, R5 and R6 are each a member independently selected from the group consisting of the following: (a) â€”H; â€”F; â€”Cl; â€”(C2-C4)alkynyl; â€”R16; â€”OR16; â€”S(&boxH;O)pR16; â€”OC(&boxH;O)R16; â€”C(&boxH;O)OR16; â€”C(&boxH;O)R16; â€”CN; â€”NO2; â€”C(&boxH;O)NR16R17; â€”OC(&boxH;O)NR16R17; â€”NR22aC(&boxH;O)NR16R17; â€”NR22aC(&boxH;NR12)NR16R17; â€”NR22aC(&boxH;NCN)NR16R17; â€”NR22aC(&boxH;Nâ€”NO2)NR16R17; â€”C(&boxH;NR22a)NR16R17; â€”CH2C(&boxH;NR22a)NR16R17; â€”OC(&boxH;NR22a)NR16R17; â€”OC(&boxH;Nâ€”NO2)NR16R17; â€”NR16R17; â€”CH2NR16R17; NR22aC(&boxH;O)R16; â€”NR22aC(&boxH;O)OR16; &boxH;NOR16; â€”NR22aS(&boxH;O)pR17; â€”S(&boxH;O)pNR16R17; and â€”CH2C(&boxH;NR22a)NR16R17; where p is 0, 1, or 2; and R22a, R16, and R17 have the same meanings as defined above; (b) â€”(C1-C4)alkyl; and â€”(C1-C4)alkoxy in the case where one or more of R4, R5, or R6 has the meaning of â€”OR16 under (a) above and R16 is defined as â€”(C1-C4)alkyl; wherein said alkyl and 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 (c) an aryl or heterocyclyl moiety selected from the group consisting of phenyl; benzyl; 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 aryl and heterocyclyl moieties are each independently substituted with 0 to 2 substituents R14; where R14 is a member selected from the group consisting of â€”(C1-C4)alkyl; â€”(C3-C7)cycloalkyl; phenyl; benzyl; pyridyl; and quinolinyl; where said alkyl, cycloalkyl, phenyl, benzyl, pyridyl, or quinolinyl is substituted by 0, 1, or 2 substituents â€”F, â€”Cl, â€”CH3, â€”OR16, â€”NO2, â€”CN, or â€”NR16R17; and said R14 group further consists of â€”F; â€”Cl; â€”CF3; oxo(&boxH;O); â€”OR16; â€”NO2; â€”CN; â€”C(&boxH;O)OR16; â€”Oâ€”C(&boxH;O)R16; â€”C(&boxH;O)NR16R17; â€”Oâ€”C(&boxH;O)NR16R17; â€”NR16R17; â€”NR16C(&boxH;O)R17; â€”NR16C(&boxH;O)OR17; â€”NR16S(&boxH;O)R17; or â€”S(&boxH;O)2NR16R17; where R16 and R17 have thesame meanings as defined above; and further where R15 is a member independently selected from the group consisting of â€”H; â€”C(&boxH;O)R16; â€”OR16; â€”(C1-C4)alkylk-OR16; â€”C(&boxH;O)OR16; â€”(C1-C2)alkyl-C(&boxH;O)OR16; â€”C(&boxH;O)NR16R17; â€”(C1-C4)alkyl; â€”(C2-C4)alkenyl; â€”(CH2)uâ€”(C3-C7)cycloalkyl where u is 0, 1 or 2; phenyl; benzyl; pyridyl; and quinolinyl; wherein said alkyl, alkenyl, alkoxy, cycloalkyl, phenyl, benzyl, pyridyl or quinolinyl is substituted with 0 to 3 substituents R12; where R16 and R17 have the same meanings as defined above; and where R12 is a member independently selected from the group consisting of â€”F; â€”Cl; â€”CO2R18; â€”OR16; â€”CN; â€”C(&boxH;O)NR18R19; â€”NR18R19; â€”NR18C(&boxH;O)R19; â€”NR18C(&boxH;O)OR19; â€”NR18S(&boxH;O)pR19; â€”S(&boxH;O)pNR18R19, where p is 1 or 2; â€”(C1-C4)alkyl; and â€”(C1-C4)alkoxy in the case where R12 has the meaning of â€”OR16 above and R16 is defined as â€”(C1-C4)alkyl; wherein said alkyl and alkoxy are each independently substituted with 0 to 3 substituents independently selected from â€”F; â€”Cl; â€”(C1-C2)alkoxycarbonyl; â€”(C1-C2)alkylcarbonyl; and â€”(C1-C2)alkylcarbonyloxy; where R16 has the same meaning as defined above; and where R18 and R19 are independently selected from the group consisting of â€”H; â€”(C1-C4)alkyl; and phenyl; where said alkyl or phenyl is substituted by 0-3 of â€”F; or â€”Cl; or in the case where G1 is phenyl (d) R5 and R6 are taken together to form a moiety which is a member selected from the group consisting of partial Formulas (1.3.1) through (1.3.15): whereinR20 and R21 are each a member independently selected from the group consisting of â€”H; â€”F; â€”Cl; CH3; â€”CH2F; CHF2; CF3; â€”OCH3; and OCF3; R23 and R24 are each independently â€”H; â€”CH3; â€”OCH3; â€”CH2CH3; â€”OCH2CH3; â€”CH2CH2CH3; â€”CH2(CH3)2; â€”CH2CH2CH2CH3; â€”CH(CH3)CH2CH3; â€”CH2CH(CH3)2; â€”C(CH3)3; or absent, in which case the dashed line - - - - represents a double bond; G1 is a saturated or unsaturated carbon ring system that is a 3- to 7-membered monocyclic, or that is a 7- to 12-membered, fused polycyclic; provided that G1 is not a discontinuous or restricted biaryl moiety as defined under G2 below; and wherein optionally one carbon atom of said carbon ring system may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionrally a third carbon atom thereof may be replaced by N; wherein said moiety defining G1 is substituted on any ring or rings thereof by R4, R5 and R6, which have the same meaning as defined above; G2 is a saturated or unsaturated carbon-ring system that is a 3- to 7-membered monocyclic; or that is a 7- to 12-membered, fused polycyclic; or that is a 7- to 18-membered discontinuous or restricted biaryl moiety; wherein for each of the carbon ring systems recited, optionally one carbon atom of said carbon ring system may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; wherein said moiety defining G2 is substituted on any ring or rings thereof by R1 and R2, which have the same meanings as-defined above; E is a member independently selected from the group consisting of the following (a) the group consisting of partial Formulas (1.1.1) through (1.1.15): whereinwhere R16 and R17 have the same meanings as defined above; and R9 has the same meaning as defined below; â€œ*â€  indicates the point of attachment of each partial Formula (1.1.1) through (1.1.15) to the remaining portion of Formula (1.0.0); q is 1, 2, or 3, provided that where q is 2 or 3, R9 has the meaning of â€”H in at least one instance, or two instances, respectively; v is 0 or 1; W3 is â€”Oâ€”; â€”N(R9)â€”, where R9 has the same meaning as defined below; or â€”OC(&boxH;O)â€”; R7A is a member independently selected from the group consisting of the following: (1) â€”H; (2) â€”(C1-C6)alkyl; â€”(C2-C6)alkenyl; or â€”(C2-C6)alkynyl; where said alkyl, alkenyl or alkynyl is substituted by 0 to 3 substituents R10, where R10 has the same meaning as defined above; (3) â€”(CH2)uâ€”(C3-C7)cycloalkyl where u is 0, 1 or 2; and further where said (C3-C7)cycloalkyl is substituted by 0 to 3 substituents R10 where R10 has the same meaning as defined above; and (4) phenyl or benzyl or pyridyl, where said phenyl, benzyl, or pyridyl is independently substituted. by 0 to 3 substituents R10 where R10 has the same meaning as defined above; R7B is a member independently selected from the group consisting of the following: (1) tetrazol-5-yl; 1,2,4-triazol-3-yl; 1,2,4-triazol-3-on-5-yl; 1,2,3-triazol-5-yl; imidazol-2-yl; imidazol-4-yl; imidazolidin-2-on-4-yl; 1,3,4-oxadiazolyl; 1,3,4-oxadiazol-2-on-5-yl; 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-on-3-yl; 1,2,4-oxadiazbl-5-yl; 1,2,4-oxadiazol-3-on-5-yl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; morpholinyl; parathiazinyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; pyrazolyl; succinimidyl; glutarimidyl; pyrrolidonyl; 2-piperidonyl; 2-pyridonyl; 4-pyridonyl; pyridazin-3-onyl; pyridyl; pyrimidinyl; pyrazinyl; pyridazinyl; and (2) indolyl; indolinyl; isbindolinyl; benzo[b]furanyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; 2H-1-benzopyranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzothiazolyl; benzotriazolyl; benzotriazinyl; phthalazinyl; 1,8-naphthyridinyl; quinolinyl; isoquinolinyl; quinazolinyl; quinoxalinyl; pyrazolo[3,4-d]pyrimidinyl; pyrimido[4,5-d]pyrimidinyl; imidazo[1,2-a]pyridinyl; pyridopyridinyl; pteridinyl; and 1H-purinyl; where any moiety recited in (1) or (2) above is optionally substituted with respect to (i) any one or more carbon atoms thereof optionally by a substituent R14 where R14 has the same meaning as defined above; (ii) any one or more nitrogen atoms thereof that is not a point of attachment of said moiety, optionally by a substituent R15 where R15 has the same meaning as defined above, and all tautomer forms thereof; and (iii) any sulfur atom thereof that is not a point of attachment of said moiety, by 0, 1, or 2 oxygen atoms; R9 is a member selected from the group consisting of â€”H; â€”(C1-C4)alkyl; â€”(C3-C7)cycloalkyl; phenyl; benzyl; pyridyl; â€”C(&boxH;O)OR16; â€”C(&boxH;O)R16; â€”OR16; â€”(C1-C2)alkykâ€”OR16; and â€”(C1-C2)alkyl-C(&boxH;O)OR16; where R16 has the same meaning as defined above; R7C is a member independently selected from the group consisting of the meanings of R7A and the meanings of R7B defined above; and further wherein comprises a saturated or unsaturated, 4- to 8-membered monocyclic, or 5- to 10-membered fused or open bicyclic, carbocyclic ring system containing a nitrogen heteroatom as shown in partial Formula (1.1.15); wherein optionally from 1 to 3 carbon atoms of said carbocyclic ring system may be individually replaced by a nitrogen heteroatom; or optionally 1 carbon atom thereof may be replaced by an oxygen heteroatom or by a sulfur heteroatom; or optionally 2 carbon atoms thereof may be individually replaced by a nitrogen heteroatom and an oxygen heteroatom, or by a nitrogen heteroatom and a sulfur heteroatom; whereany moiety of partial Formula (1.1.15) recited above is optionally substituted with respect to (1)any one or more carbon atoms thereof, by a substituent R14 where R14 has the same meaning as defined above; (2) any one or more nitrogen atoms thereof by a substituent R15 where R15 has the same meaning as defined above, and all tautomer forms, and optionally N-oxide forms thereof; or (3) any sulfur atom thereof by 0, 1, or 2 oxygen atoms; and E is further selected from (b) a moiety comprising a member selected from the group consisting of â€”Oâ€”P(&boxH;O)(OH)2(phosphoric); â€”PH(&boxH;O)OH(phosphinic); â€”P(&boxH;O)(OH)2(phosphonic); â€”[P(&boxH;O)(OH)â€”O(C1-C4)alkyl](alkylphosphono); â€”P(&boxH;O)(OH)â€”O(C1-C4)alkyl)(alkylphosphinyl); â€”P(&boxH;O)(OH)NH2(phosphoramido); â€”P(&boxH;O)(OH)NH(C1-C4)alkyl and â€”P(&boxH;O)(OH)NHR25(substituted phosphoramido); â€”P(&boxH;O)(OH)NH(C1-C4)alkyl and â€”P(&boxH;O)(OH)NHR25(substituted phosphoramido); â€”Oâ€”S(&boxH;O)2OH(sulfuric); â€”S(&boxH;O)2OH(sulfonic); â€”S(&boxH;O)2NHR26 or â€”NHS(&boxH;O)2R26(sulfonamido) where R26 is â€”CH3, â€”CF3, or o-toluyl; and acylsulfonamido selected from the group consisting of â€”C(&boxH;O)NHS(&boxH;O)2R25; â€”C(&boxH;O)NHS(&boxH;O)2NH2; â€”C(&boxH;O)NHS(&boxH;O)2(C1-C4)alkyl; â€”C(&boxH;O)NHS(&boxH;O)2NH(C1-C4)alkyl; â€”C(&boxH;O)NHS(&boxH;O)2N[(C1-C4)alkyl]2; â€”S(&boxH;O)2NHC(&boxH;O)(C1-C4)alkyl; â€”S(&boxH;O)2NHC(&boxH;O)NH2; â€”S(&boxH;O)2NHC(&boxH;O)NH(C1-C4)alkyl; â€”S(&boxH;O)2NHC(&boxH;O)N[(C1-C4)alkyl]2; â€”S(&boxH;O)2NHC(&boxH;O)R25; â€”S(&boxH;O)2NHCN; â€”S(&boxH;O)2NHC(&boxH;S)NH2; â€”S(&boxH;O)2NHC(&boxH;S)NH(C1-C4)alkyl; â€”S(&boxH;O)2NHC(&boxH;S)N[(C1-C4)alkyl]2; and â€”S(&boxH;O)2NHS(&boxH;O)2R25; where R25 is â€”H; â€”(C1-C4)alkyl; phenyl; or â€”OR18, where R18 has the same meaning as defined above; or a pharmaceutically acceptable salt thereof.