초록 ▼

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to phar

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

대표청구항 ▼

[ We claim:] [1.]1. A compound of formula I: a pharmaceutically acceptable salt thereof, wherein:E' is --SO.sub.2 --;A is --R.sup.1 --Ht;R.sup.1 is --O--C(O)--;Ht is a 5-membered saturated or unsaturated heterocycle, containing one or more oxygen; wherein said heterocycle is optionally fused to Q; a

[ We claim:] [1.]1. A compound of formula I: a pharmaceutically acceptable salt thereof, wherein:E' is --SO.sub.2 --;A is --R.sup.1 --Ht;R.sup.1 is --O--C(O)--;Ht is a 5-membered saturated or unsaturated heterocycle, containing one or more oxygen; wherein said heterocycle is optionally fused to Q; and wherein said Ht is optionally substituted with one or more substituents independently selected from oxo, --OR.sup.2, SR.sup.2, --R.sup.2, --N(R.sup.2)(R.sup.2), --R.sup.2 --OH, --CN, --CO.sub.2 R.sup.2, --C(O)--N(R.sup.2).sub.2, --S(O).sub.2 --N(R.sup.2).sub.2, --N(R.sup.2)--C(O)--R.sup.2, --N(R.sup.2)--C(O)O--R.sup.2, --C(O)--R.sup.2, --S(O).sub.n --R.sup.2, --OCF.sub.3, --S(O).sub.n --Q, methylenedioxy, --N(R.sup.2)--S(O).sub.2 (R.sup.2), halo, --CF.sub.3, --NO.sub.2, Q or --OQ;each Q is independently selected from a 3-7 membered saturated, partially saturated or unsaturated carbocyclic ring system; or a 5-7 membered saturated, partially saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from O, N, or S; wherein Q is optionally substituted with one or more groups selected from oxo, --OR.sup.2, --R.sup.2, --SO.sub.2 R.sup.2, --SO.sub.2 --N(R.sup.2).sub.2, --N(R.sup.2).sub.2, --N(R.sup.2)--C(O)--R.sup.2, --R.sup.2 --OH, --CN, --CO.sub.2 R.sup.2, --C(O)--N(R.sup.2).sub.2, halo, --CF.sub.3 ;each R.sup.2 is independently selected from H, or C.sub.1 -C.sub.4 alkyl; and wherein said alkyl, when not a substituent of Q, is optionally substituted with Q or --OR.sup.3 ; wherein when said R.sup.2 is an --OR.sup.3 substituted moiety, said R.sup.3 in --OR.sup.3 may not be --OR.sup.2 substituted;B, when present, is --N(R.sup.2)--C(R.sup.3).sub.2 --C(O)--;each x is independently 0 or 1;each R.sup.3 is independently selected from H, Ht, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.6 cycloalkyl or C.sub.5 -C.sub.6 cycloalkenyl; wherein any member of said R.sup.3, except H, is optionally substituted with one or more substituents selected from --OR.sup.2, --C(O)--NH--R.sup.2, --S(O).sub.n --N(R.sup.2)(R.sup.2), --N(R.sup.2).sub.2, --N(R.sup.2)--C(O)--O(R.sup.2), --N(R.sup.2)--C(O)--N(R.sup.2), --N(R.sup.2)--C(O)--(R.sup.2), Ht, --CN, --SR.sup.2, --CO.sub.2 R.sup.2, or NR.sup.2 --C(O)--R.sup.2 ;each n is independently 1 or 2;G, when present, is selected from R.sup.7 or C.sub.1 -C.sub.4 alkyl, or, when G is C.sub.1 -C.sub.4 alkyl, G and R.sup.7 are optionally bound to one another through a C.sub.1 -C.sub.3 linker to form a heterocyclic ring;D is selected from Q; C.sub.1 -C.sub.6 alkyl optionally substituted with one or more groups selected from C.sub.3 -C.sub.6 cycloalkyl, --OR.sup.2, --S--Ht, --R.sup.3, --O--Q or Q; C.sub.2 -C.sub.4 alkenyl optionally substituted with one or more groups selected from --OR.sup.2, --S--Ht, --R.sup.3, --O--Q or Q; C.sub.3 -C.sub.6 cycloalkyl optionally substituted with or fused to Q; or C.sub.5 -C.sub.6 cycloalkenyl optionally substituted with or fused to Q;D' is selected from C.sub.1 -C.sub.15 alkyl, C.sub.2 -C.sub.15 alkenyl or C.sub.2 -C.sub.15 alkynyl, each of which contains one or more substituents selected from oxo, halo, --CF.sub.3, --OCF.sub.3, --NO.sub.2, azido, --SH, --SR.sup.3, --N(R.sup.3)--N(R.sup.3).sub.2, --O--N(R.sup.3).sub.2, --(R.sup.3)N--O--(R.sup.3), --N(R.sup.3).sub.2, --CN, --CO.sub.2 R.sup.3, --C(O)--N(R.sup.3).sub.2, --S(O).sub.n --N(R.sup.3).sub.2, --N(R.sup.3)--C(O)--R.sup.3, --N(R.sup.3)--C(O)--N(R.sup.3).sub.2, --N(R.sup.3)--C(O)--S(R.sup.3), --C(O)--R.sup.3, --S(O).sub.n --R.sup.3, --N(R.sup.3)--S(O).sub.n (R.sup.3), --N(R.sup.3)--S(O).sub.n --N(R.sup.3).sub.2, --S--NR.sup.3 --C(O)R.sup.3, --C(S)N(R.sup.3).sub.2, --C(S)R.sup.3, --NR.sup.3 --C(O)OR.sup.3, --O--C(O)OR.sup.3, --O--C(O)N(R.sup.3).sub.2, --NR.sup.3 --C(S)R.sup.3, .dbd.N--OH, .dbd.N--OR.sup.3, .dbd.N--N(R.sup.3).sub.2, .dbd.NR.sup.3, .dbd.NNR.sup.3 C(O)N(R.sup.3).sub.2, .dbd.NNR.sup.3 C(O)OR.sup.3, .dbd.NNR.sup.3 S(O).sub.n --N(R.sup.3).sub.2, --NR.sup.3 --C(S)OR.sup.3, --NR.sup.3 --C(S)N(R.sup.3).sub.2, --NR.sup.3 --C[.dbd.N(R.sup.3)]--N(R.sup.3).sub.2, --N(R.sup.3)--C[.dbd.N--NO.sub.2 ]--N(R.sup.3).sub.2, --N(R.sup.3)--C[.dbd.N--NO.sub.2 ]--OR.sup.3, --N(R.sup.3)--C[.dbd.N--CN]--OR.sup.3, --N(R.sup.3)--C[.dbd.N--CN]--(R.sup.3).sub.2, --OC(O)R.sup.3, --OC(S)R.sup.3, --OC(O)N(R.sup.3).sub.2, --C(O)N(R.sup.3)--N(R.sup.3).sub.2, --O--C(O)N(R.sup.3)--N(R.sup.3).sub.2, O--C(O)N(OR.sup.3)(R.sup.3), N(R.sup.3)--N(R.sup.3)C(O)R.sup.3, N(R.sup.3)--OC(O)R.sup.3, N(R.sup.3)--OC(O)R.sup.3, N(R.sup.3)--OC(O)R.sup.3, --OC(S)N(R.sup.3).sub.2, --OC(S)N(R.sup.3)(R.sup.3), or PO.sub.3 --R.sup.3 ;E is benzodioxole, which is optionally substituted with one or more substituents independently selected from oxo, --OR.sup.2, SR.sup.2, --R.sup.2, --N(R.sup.2)(R.sup.2), --R.sup.2 --OH, --CN, --CO.sub.2 R.sup.2, --C(O)--N(R.sup.2).sub.2, --S(O).sub.2 --N(R.sup.2).sub.2, --N(R.sup.2)--C(O)--R.sup.2, --N(R.sup.2)--C(O)O--R.sup.2, --C(O)--R.sup.2, --S(O).sub.n --R.sup.2, --OCF.sub.3, --S(O).sub.n --Q, methylenedioxy, --N(R.sup.2)--S(O).sub.2 (R.sup.2), halo, --CF.sub.3, --NO.sub.2, Q or --OQ; andeach R.sup.7 is hydrogen.