Patent ID: 6251912
Filing Date: 2001-06-26
Classification: C07D

Abstract:
A compound of formula 1 having the structure ##STR31##wherein:X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring 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, 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, carboalkoxyalky of 3-8 carbon atoms, aminomethyl, N-alkylaminomethyl of 2-7 carbon atoms, N,N-dialkylaminomethyl of 3-7 carbon atoms, mercapto, methylmercapto, and benzoylamino;Z is --NH--, --O--, --S--, or --NR--;R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms;R.sub.1, R.sub.3, and R.sub.4 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 1-6 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, 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,R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-W--(C(R.sub.6).sub.2).sub.k --Y--Y is a divalent radical selected from the group consisting of ##STR32##R.sub.7 is --NR.sub.6 R.sub.6, or --OR.sub.6 ;M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.p NR.sub.6 R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p --OR.sub.6 ;W is >NR.sub.6, --O-- or is a bond;Het is a heterocycle, optionally mono- or di-substituted on carbon or nitrogen with R.sub.6 and optionally mono-substituted on carbon with --CH.sub.2 OR.sub.6 ; wherein the heterocycle is selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, piperazine, tetrahydrofuran, and tetrahydropyran;R.sub.6 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, 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;R.sub.2, is selected from the group consisting of ##STR33## ##STR34##R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-W--(C(R.sub.6).sub.2).sub.r --;R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.r NR.sub.6 R.sub.6, or --(C(R.sub.6).sub.2).sub.r OR.sub.6 ;J is independently hydrogen, chlorine, fluorine, or bromine;Q is alkyl of 1-6 carbon atoms or hydrogen;a=0 or 1;g=1-6;k=0-4;n is 0-1;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 that when:Z is NH;n is 0;R.sub.2 is selected from the group consisting of ##STR35##R.sub.5 is independently and exclusively hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, or carboalkyl of 2-7 carbon atoms;R.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, or alkoxy of 1-6 carbon atoms;R.sub.4 is hydrogen, halogen, alkyl of 1-6 carbon atoms, or alkoxy of 1-6 carbon atoms; andR.sub.3 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, or trifluoromethyl;X is not an unsubstituted phenyl ring, or a phenyl ring exclusively substituted with one or more substitutents selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, amino, and alkanoylamino of 1-6 carbon atoms;further provided that when R.sub.2 is ##STR36##and R.sub.5 is hydrogen or alkyl of 1-6 carbon atoms,R.sub.3 is not halogen;and still further provided thatwhen R.sub.6 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 finally provided thatwhen Y is --NR.sub.6 -- or R.sub.7 is --NR.sub.6 R.sub.6 then g=2-6;when M is --O-- and R.sub.7 is --OR.sub.6 then p=1-4;when Y is --NR.sub.6 -- then k=2-4;when Y is --O-- and M or W is --O-- then k=1-4and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6 -- then k=2-4.