[미국특허]
Sulfonamide inhibitors of aspartyl protease
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07D-040/712
C07C-030/300
A61K-031/34
출원번호
US-0477937
(1995-06-07)
발명자
/ 주소
Tung Roger D.
Murcko Mark A.
Bhisetti Govinda R.
출원인 / 주소
Vertex Pharmaceuticals, Incorporated
대리인 / 주소
Fish & NeaveHaley, Jr.
인용정보
피인용 횟수 :
22인용 특허 :
4
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.] A compound of formula I: [ STR 610 ] wherein: A is selected from the group consisting of Het; --R.sup.1 --Het; --R.sup.1 --C.sub.1 -C.sub.6 alkyl, which is substituted with one to two groups selected from the group consisting of Het and --O--Het; and --R.sup.1 --C.sub.2 -C.sub.6 al
[ We claim:] [1.] A compound of formula I: [ STR 610 ] wherein: A is selected from the group consisting of Het; --R.sup.1 --Het; --R.sup.1 --C.sub.1 -C.sub.6 alkyl, which is substituted with one to two groups selected from the group consisting of Het and --O--Het; and --R.sup.1 --C.sub.2 -C.sub.6 alkenyl, which is substituted with one to two groups selected from the group consisting of Het and --O--Het;each R.sup.1 is independently selected from the group consisting of --C(O)--, --S(O).sub.2, --C(O)--C(O)--, --O--C(O)--, --O--S(O).sub.2, --NR.sup.2 --S(O).sub.2 --, --NR.sup.2 --C(O)-- and --NR.sup.2 --C(O)--C(O)--;each Het is independently selected from the group consisting of 5-7 membered saturated or unsaturated heterocycle, containing one or more heteroatoms selected from O, S and S(O).sub.n, wherein said heterocycle may optionally be benzofused; and wherein any member of said Het may be optionally substituted with one to two substituents selected from the group consisting of oxo, --OR.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) (R.sup.2), --S(O).sub.2 --N(R.sup.2) (R.sup.2), --N(R.sup.2)--C(O)--R.sup.2, --C(O)--R.sup.2, --S(O).sub.n --R.sup.2, --OCF.sub.3, --S(O).sub.n --Ar, methylenedioxy, --N(R.sup.2)--S(O).sub.2 (R.sup.2), halo, --CF.sub.3, --NO.sub.2, Ar and --O--Ar;each R.sup.2 is independently selected from the group consisting of H and C.sub.1 -C.sub.3 alkyl optionally substituted with Ar; with the proviso that when R.sup.2 is C.sub.1 -C.sub.3 alkyl substituted with Ar, said Ar may not be substituted with an Ar-containing moiety;B, when present, is --N(R.sup.2)--C(R.sup.3) (R.sup.3)--C(O)--;x is 0 or 1;each R.sup.3 is independently selected from the group consisting of H, Het, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 cycloalkyl and C.sub.5 -C.sub.6 cycloalkenyl, wherein any member of said R.sup.3, except H, may be optionally substituted with one to two substituents selected from the group consisting of --OR.sup.2, --C(O)--NH--R.sup.2, --S(O).sub.n --N(R.sup.2) (R.sup.2), Het, --CN, --SR.sup.2, --CO.sub.2 R.sup.2, NR.sup.2 --C(O) --R.sup.2 ;each n is independently 1 or 2;D and D' are independently selected from the group consisting of Ar; C.sub.1 -C.sub.4 alkyl, which may be optionally substituted with one to two groups selected from C.sub.3 -C.sub.6 cycloalkyl, --OR.sup.2, --R.sup.3, --O--Ar and Ar; C.sub.2 -C.sub.4 alkenyl, which may be optionally substituted with one to two groups selected from the group consisting of C.sub.3 -C.sub.6 cycloalkyl, --OR.sup.2, --R.sup.3, --O--Ar and Ar; C.sub.3 -C.sub.6 cycloalkyl, which may be optionally substituted with or fused with Ar; and C.sub.5 -C.sub.6 cycloalkenyl, which may be optionally substituted with or fused with Ar;each Ar is independently selected from the group consisting of phenyl; 3-6 membered carbocyclic ring and 5-6 membered heterocyclic ring containing one or more heteroatoms selected from O, S, and S(O).sub.n, wherein said carbocyclic or heterocyclic ring may be saturated or unsaturated and optionally substituted with one to two groups selected from the group consisting of oxo, --OR.sup.2, --R.sup.2, --N(R.sup.2) (R.sup.2), --N(R.sup.2)--C(O)--R.sup.2, C.sub.1 -C.sub.3 alkyl substituted with --OH and optionally substituted with Ar, --CN, --CO.sub.2 R.sup.2, --C(O)--N(R.sup.2) (R.sup.2), halo and --CF.sub.3 ;E is selected from the group consisting of Het; O--Het; Het--Het; C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 saturated carbocycle and C.sub.5 -C.sub.6 unsaturated carbocycle, each of which is substituted with one to two Het groups.
Kempf Dale J. (Libertyville IL) Norbeck Daniel W. (Lindenhurst IL) Codacovi Lynn M. (Antioch IL) Plattner Jacob J. (Libertyville IL) Sham Hing L. (Gurnee IL) Zhao Chen (Gurnee IL), Retroviral protease inhibiting compounds.
Michael L Vazquez ; Richard A Mueller ; John J Talley ; Daniel P Getman ; Gary A DeCrescenzo ; Eric T Sun, .alpha.- and .beta.-amino acid hydroxyethylamino sulfamic acid derivatives useful as retroviral protease inhibitors.
Vazquez Michael L. ; Mueller Richard A. ; Talley John J. ; Getman Daniel P. ; DeCrescenzo Gary A. ; Freskos John N. ; Bertenshaw Deborah E. ; Heintz Robert M., .alpha.- and .beta.-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Michael L. Vazquez ; Richard A. Mueller ; John J. Talley ; Daniel P. Getman ; Gary A. DeCrescenzo ; John N. Freskos ; Deborah E. Bertenshaw ; Robert M. Heintz, .alpha.-and .beta.-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Vazquez Michael L ; Mueller Richard A ; Talley John J ; Getman Daniel P ; DeCrescenzo Gary A ; Sun Eric T, Alpha- and beta-amino acid hydroxyethylamino sulfamic acid derivatives useful as retroviral protease inhibitors.
Tung, Roger Dennis; Hale, Michael Robin; Baker, Christopher Todd; Furfine, Eric Steven; Kaldor, Istvan; Kazmierski, Wieslaw Mieczylaw; Spaltenstein, Andrew, Sulphonamide derivatives as prodrugs of aspartyl protease inhibitors.
Tung, Roger Dennis; Hale, Michael Robin; Baker, Christopher Todd; Furfine, Eric Steven; Kaldor, Istvan; Kazmierski, Wieslaw Mieczylaw; Spaltenstein, Andrew, Sulphonamide derivatives as prodrugs of aspartyl protease inhibitors.
Vazquez, Michael L.; Mueller, Richard A.; Talley, John J.; Getman, Daniel P.; DeCrescenzo, Gary A.; Freskos, John N.; Heintz, Robert M.; Bertenshaw, Deborah E., α- and β- amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Vazquez, Michael L.; Mueller, Richard A.; Talley, John J.; Getman, Daniel P.; DeCrescenzo, Gary A.; Freskos, John N.; Bertenshaw, Deborah E.; Heintz, Robert M., α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Vazquez, Michael L.; Mueller, Richard A.; Talley, John J.; Getman, Daniel P.; DeCrescenzo, Gary A.; Freskos, John N.; Bertenshaw, Deborah E.; Heintz, Robert M., α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Vazquez, Michael L.; Mueller, Richard A.; Talley, John J.; Getman, Daniel P.; DeCrescenzo, Gary A.; Freskos, John N.; Bertenshaw, Deborah E.; Heintz, Robert M., α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Vazquez, Michael L.; Mueller, Richard A.; Talley, John J.; Getman, Daniel P.; DeCrescenzo, Gary A.; Freskos, John N.; Heintz, Robert M.; Bertenshaw, Deborah E., α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
Vazquez, Michael L.; Mueller, Richard A.; Talley, John J.; Getman, Daniel P.; DeCrescenzo, Gary A.; Freskos, John N.; Bertenshaw, Deborah E.; Heintz, Robert M., α-and β-Amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.