Patent ID: 6548496
Filing Date: 2003-04-15
Classification: A61K,A61P,C07D

Abstract:
A compound of formula I having the structure wherein:X is the radical E is Ph; T is substituted on E at carbon and is â€”NH(CH2)mâ€”, â€”NR(CH2)mâ€”, â€”CH2)mNHâ€”, or â€”(CH2)mNRâ€”; L is a 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S; wherein the heteroaryl ring may be optionally mono- or di-substituted with a substituent selected from the group consisting of halogen, oxo, thio, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Ph is phenyl, which may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is â€”NHâ€”; Aâ€³ is a diavalent moiety selected from the group G1, G2, G3, and G4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 2-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, R2NH, â€ƒR7â€”(C(R6)2)gâ€³Yâ€”, R7â€”(C(R6)2)pâ€”Mâ€”(C(R6)2)kâ€”Yâ€”, Het-(C(R6)2)qâ€”Wâ€”(C(R6)2)kâ€”Yâ€”, with the proviso that G3 and G4 are not R2NH; Y is a divalent radical selected from the group consisting of R7 is â€”NR6R6, â€”OR6, â€”J, â€”N(R6)3+, or â€”NR6(OR6); M is >NR6, â€”Oâ€”, >Nâ€”(C(R6)2)pNR6R6, or >Nâ€”(C(R6)2)pâ€”OR6; W is >NR6, â€”Oâ€” or is a bond; Het is a heterocyclic radical selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane tetrahydropyran, and which may be optionally mono- or di-substituted on carbon with R6, hydroxy, â€”N(R6)2, â€”OR6â€”(C(R6)2)sOR6 or â€”(C(R6)2)sN(R6)2; optionally mono-substituted on nitrogen with R6; and optionally mono or di-substituted on a saturated carbon with divalent radicals â€”Oâ€” or â€”O(C(R6)2)sOâ€”; R6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl 2-7 carbon atoms, phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; R2, is selected from the group consisting of R3 is hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, â€ƒR7â€”(C(R6)2)sâ€”, R7(C(R6)2)pâ€”Mâ€”(C(R6)2)râ€”, â€ƒR8R9â€”CHâ€”Mâ€”(C(R6)2)râ€”, or Het-(C(R6)2)qâ€”Wâ€”(C(R6)2)râ€”; R5 is hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, â€ƒR7â€”(C(R6)2)sâ€”, R7â€”(C(R6)2)pâ€”Mâ€”(C(R6)2)râ€”, â€ƒR8R9â€”CHâ€”Mâ€”(C(R6)2)râ€”, or Het-(C(R8)2)qâ€”Wâ€”(C(R6)2)râ€”; R8, and R9 are each, independently, â€”(C(R6)2)rNR6R6, or â€”(C(R6)2)rOR6; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0-1; g=1-6; k=0-4; n is 0-1; m is 0-3; p=2-4; q=0-4; r=1-4; s=1-6; u=0-4 and v=0-4, wherein the sum of u+v is 2-4; or a pharmaceutically acceptable salt thereof,provided thatwhen R6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and provided thatwhen R3 is bound to sulfur, it cannot be hydrogen, carboxy, carboalkoxy, or carboalkyl; and provided thatwhen Y is â€”NR6â€” and R7 is â€”NR6R6, â€”N(R6)3+, or â€”NR6(OR6), then g=2-6; when M is â€”Oâ€” and R7 is â€”OR6 then p=1-4; when Y is â€”NR6â€” then k=2-4; when Y is â€”Oâ€” and M or W is â€”Oâ€” then k=1-4 when W is not a bond with Het bonded through a nitrogen atom then q=2-4 and when W is a bond with Het bonded through a nitrogen atom and Y is â€”Oâ€” or â€”NR6â€” then k=2-4; and finally provided thatwhen Aâ€³ is the moiety n=0, Z is NH, G1 is hydrogen, halogen, alkyl, alkoxy, hydroxy, alkanoyloxy of 2-6 carbon atoms, or phenoxy, and G2 is hydrogen, halogen, alkyl, hydroxy, carboxyalkyl, carboalkoxyalkyl, hydroxyalkyl, alkoxy, halomethyl, carboxyl, carboalkoxy, alkanoylamino, or alkenoylamino, then X can not be a phenyl ring that is substituted with a hydroxy or alkoxy group.