Patent ID: 6441015
Filing Date: 2002-08-27
Classification: A61P,C07D

Abstract:
A compound of Formula I or a stereoisomer, or a pharmaceutically acceptable salt thereof wherein:W is O, S, SO, SO2, CH2, CF2, CHF, C(&boxH;O), CH(OH), NRa, or X is O, CH2, CH2CH2, S, SO, SO2, CH2NRa, NRa or a bond; each Ra is independently hydrogen, C1-C6alkyl, or C1-C6alkyl substituted with one substituent selected from C3-C6cycloalkyl or methoxy; R1, R2, R3 and R6 are independently hydrogen, halogen, C1-C8alkyl, â€”CF3, â€”OCF3, â€”OC1-C8alkyl, or â€”CN; R4 is hydrogen, C1-C12alkyl, C1-C12alkyl that is substituted with from one to three substituents independently selected from Group V, C2-C12 alkenyl, C2-C12 alkynyl, halogen, â€”CN, â€”ORb, â€”SRc, â€”S(&boxH;O)Rc, â€”S(&boxH;O)2Rc, aryl, heteroaryl, C3-C10 cycloalkyl, heterocycloalkyl, â€”S(&boxH;O)2NRcRd, â€”C(&boxH;O)NRcRd, â€”C(&boxH;O)ORc, â€”NRaC(&boxH;O)Rd, â€”NRaC(&boxH;O)NRcRd, â€”NRaS(&boxH;O)2Rd, â€”NRaRd, â€”C(&boxH;O)Rc, or R3 and R4 are taken together with the carbon atoms to which they are attached to form an unsubstituted or substituted carbocyclic ring of formula â€”(CH2)iâ€” or an unsubstituted or substituted heterocyclic ring selected from the group consisting of â€”Qâ€”(CH2)jâ€” and â€”(CH2)kâ€”Qâ€”(CH2)lâ€” wherein Q is O, S or NRa; i is 3, 4, 5, 6 or 7; j is 2, 3, 4, 5, or 6; k and l are each independently 1, 2, 3, 4, or 5, and any substituents up to four are selected from C1-C4alkyl, â€”ORb, oxo, â€”CN, phenyl, or â€”NRaRg; Rb is hydrogen, C1-C12alkyl, C1-C12alkyl substituted with one to three substituents independently selected from Group V, aryl, heteroaryl, C3-C10 cycloalkyl, heterocycloalkyl, â€”C(&boxH;O)NRcRd, or â€”C(&boxH;O)Rf; Rc and Rd are each independently selected from hydrogen, C1-C12alkyl, C1-C12alkyl substituted with one to three substituents independently selected from Group VI, C2-C12alkenyl, C2-C12alkynyl, aryl, heteroaryl, C3-C10 cycloalkyl, heterocycloalkyl, or Rc and Rd may together along with the atom(s) to which they are attached form a 3-10 membered unsubstituted or substituted heterocyclic ring, which may contain a second heterogroup selected from O, NRe, or S, wherein any substitutents up to four are selected from C1-C4alkyl, â€”ORb, oxo, â€”CN, phenyl, or â€”NR Rg; R5 is â€”OH, â€”OC1-C6alkyl, â€”OC(&boxH;O)Rf, â€”F, â€”C(&boxH;O)ORc, or R4 and R5 may together with the atom(s) to which they are attached form a heterocyclic ring selected from the group consisting of â€”CRc&boxH;CRaâ€”NHâ€”, â€”N&boxH;CRaâ€”NHâ€”, â€”CRc&boxH;CRaâ€”Oâ€”, â€”CRc&boxH;CRaâ€”Sâ€”, â€”CRc&boxH;Nâ€”NHâ€”, or â€”CRa&boxH;CRaâ€”CRa&boxH;Nâ€”; Group V is halogen; â€”CF3; â€”OCF3; hydroxy; oxo; C1-C6alkoxy; â€”CN; aryl; heteroaryl; C3-C10cycloalkyl; heterocycloalkyl; â€”SR5; â€”S(&boxH;O)Rf; â€”S(&boxH;O)2Rf; â€”S(&boxH;O)2NRaRf, wherein Ra and Rf may together along with the atom(s) to which they are attached form a 3-8 membered heterocyclic ring, which may contain a second heterogroup selected from O, NRe or S; â€”NRaRg; or â€”C(&boxH;O)NRaRf, wherein Ra and Rf may together along with the atom(s) to which they are attached form a 3-8 membered heterocyclic ring, which may contain a second heterogroup selected from O, NRe or S; Group VI is halogen, hydroxy, oxo, C1-C6alkoxy, aryl, heteroaryl, C3-C8cycloalkyl, heterocycloalkyl, â€”CN, or â€”OCF3; Re is hydrogen, â€”CN, C1-C10alkyl, C1-C10alkyl substituted with one to three substitutents independently selected from Group V, C2-C10alkenyl, C2-C10alkoxy, C3-C10cycloalkyl, aryl, heteroaryl, â€”C(&boxH;O)Rf, â€”C(&boxH;O)ORf, â€”C(&boxH;O)NRaRf â€”S(&boxH;O)2NRaRf, or â€”S(&boxH;O)2Rf; Rf is hydrogen, C1-C10alkyl, C1-C10alkyl substituted with from one to three substituents selected from Group VI, C2-C10alkenyl, C2-C10alkoxy, C3-C10cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and Rg is hydrogen, C1-C6alkyl, C3-C8cycloalkyl, C2-C6 alkenyl, aryl, â€”C(&boxH;O)Rf, â€”C(&boxH;O)ORf, â€”C(&boxH;O)NRaRf, or â€”S(&boxH;O)2Rf, provided that R1 and R2 are not both hydrogen, further provided that when X is CH2, W is NRa, R3 is hydrogen and R5 is â€”OH, then R6 and R4 are not both â€”C(H3)3, further provided that when X is CH2 or CH2CH2, W is O, and R3 and R6 are hydrogen, then R4 is not halogen, â€”CF3, C1-C6alkyl or C3-C7cycloalkyl, and further provided that when R3 and R4 are hydrogen and W is O then R6 is not halogen, â€”CF3, C1-C6alkyl or C3-C7cycloalkyl.