Thiepane compounds
AssigneeGilead Sciences, Inc.
InventorsNorbert W. Bischofberger, Choung U. Kim, Steven H. Krawczyk, Lawrence R. McGee, Michael J. Postich, Wenjin Yang
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Abstract
Tri- and tetra substituted thiepane compositions having use as immunogens, therapeutics, diagnostics and for other industrial purposes are disclosed. The compositions inhibit proteolytic activity of viral enzymes and are useful for the inhibition of such enzymes as well as in assays for the detection of such enzymes. Embodiments in which antigenic polypeptides are bonded to the compositions are useful in raising antibodies against the thiepane haptens or the polypeptide. Labeled thiepanes of this invention are useful as diagnostic reagents.
Claims36
A composition comprising a compound of the formula:
- ##STR515## wherein:
- Y is independently --O--, --S--, --SO--, --SO.sub.2 --, --N(R.sub.1)--, --N(R.sub.1)--SO.sub.2 --, --N(R.sub.1)--CO--, or --O--SO.sub.2 --,
- E and U are independently H, or --CR.sub.1 R.sub.1).sub.m1 --W.sub.1, with the proviso that at least one of E and U is --CR.sub.1 R.sub.1).sub.m1 --W.sub.1 ;
- G and T are independently --CR.sub.1 R.sub.1).sub.m1 --W.sub.1, or --CR.sub.1 R.sub.1).sub.m1 --C(R.sub.1)(W.sub.1)(W.sub.2), with the provisos that:
- when E is --CR.sub.1 R.sub.1).sub.m1 --W.sub.1, then G is --CR.sub.1 R.sub.1).sub.m1 --W.sub.1 ;
- when U is --CR.sub.1 R.sub.1).sub.m1 --W.sub.1, then T is --CR.sub.1 R.sub.1).sub.m1 --W.sub.1 ;
- and G and T may be the same or different;
- J and L are independently H, N.sub.3, --OR.sub.2, --N(R.sub.2)(R.sub.2), or --N(R.sub.2)(R.sub.3), wherein R.sub.2 is H, or PRT, with the proviso that at least one of J and L is --OR.sub.2, or J and L are taken together to form an epoxide, or a cyclic protecting group;
- W.sub.1 is W.sub.2 or W.sub.3 ;
- W.sub.2 is carbocycle or heterocycle, with the proviso that each W.sub.2 is independently substituted with 0 to 3 R.sub.5 groups;
- W.sub.3 is alkyl, alkenyl, or alkynyl, with the proviso that each W.sub.3 is independently substituted with 0 to 3 R.sub.6 groups;
- R.sub.1 is R.sub.3 or R.sub.6 ;
- R.sub.3 is H or R.sub.4 ;
- R.sub.4 is alkyl;
- R.sub.5 is R.sub.6, or R.sub.7, with the proviso that each R.sub.7 is independently substituted with 0 to 3 R.sub.6 groups;
- R.sub.6 is --O-(antigenic polypeptide), --N(R.sub.3)-(antigenic polypeptide), --C(O)O-(antigenic polypeptide), --C(O)N(R.sub.3)-(antigenic polypeptide), --S-- (antigenic polypeptide), --S--S-(antigenic polypeptide), --O-(label), --N(R.sub.3)-(label), --C(O)O-(label), --C(O)N(R.sub.3)-(label), --S-(label), --S--S-(label), F, Cl, Br, I, --CN, N.sub.3, --NO.sub.2, --OR.sub.3, --OPRT, --O--C(O)R.sub.4, .dbd.O, --N(R.sub.3)(R.sub.3), --N(R.sub.3)(PRT), --N(PRT).sub.2, --N(R.sub.3)--C(O)R.sub.4, .dbd.N(R.sub.3), .dbd.N(PRT), --N(OR.sub.3)(R.sub.3), --N(OPRT)(R.sub.3), --N(OR.sub.3)(PRT), --N(OPRT)(R.sub.3), --N(N(R.sub.3)(R.sub.3))(R.sub.3), --N(N(PRT)(R.sub.3))(R.sub.3), --N(N(R.sub.3)(R.sub.3))(PRT), --N(N(PRT)(PRT))(R.sub.3), --N(N(PRT)(R.sub.3))(PRT), --N(N(PRT)(PRT))(PRT), --N(R.sub.3)--C(N(R.sub.3))(N(R.sub.3).sub.2), --N(PRT)--C(N(R.sub.3))(N(R.sub.3).sub.2), --N(R.sub.3)--C(N(PRT))(N(R.sub.3).sub.2), --N(R.sub.3)--C(N(R.sub.3))(N(R.sub.3)(PRT)), --N(PRT)--C(N(PRT))(N(R.sub.3).sub.2), --N(PRT)--C(N(R.sub.3))(N(R.sub.3)(PRT)), --N(R.sub.3)--C(N(PRT))(N(R.sub.3)(PRT)), --N(R.sub.3)--C(N(R.sub.3))(N(PRT).sub.2), --N(PRT)--C(N(PRT))(N(R.sub.3)(PRT)), --N(PRT)--C(N(R.sub.3))(N(PRT).sub.2), --N(R.sub.3)--C(N(PRT))(N(PRT).sub.2), --N(PRT)--C(N(PRT))(N(PRT).sub.2), --C(NR.sub.3)(N(R.sub.3).sub.2), --C(N(R.sub.3))(N(R.sub.3)(PRT)), --C(NPRT)(N(R.sub.3).sub.2), --C(N(PRT))(N(R.sub.3)(PRT)), --C(N(R.sub.3))(N(PRT).sub.2), --C(N(PRT))(N(PRT).sub.2), --SR.sub.3, --S(PRT), .dbd.S, --S(O)--R.sub.3, --S(O)--OR.sub.3, --S(O)--OPRT, --O--S(O)--R.sub.3, --S(O).sub.2 --R.sub.3, --S(O).sub.2 --OR.sub.3, --S(O).sub.2 --OPRT, --O--S(O).sub.2 --R.sub.3, --C(O)OR.sub.3, --C(O)OPRT, --C(O)N(R.sub.3).sub.2, --C(O)N(R.sub.3)(PRT), --C(O)N(PRT).sub.2, --C(S)N(R.sub.3).sub.2, --C(S)N(R.sub.3)(PRT), --C(S)N(PRT).sub.2, --N(R.sub.3)--S(O).sub.2 --R.sub.3, --N(PRT)--S(O).sub.2 --R.sub.3, --S(O).sub.2 --N(R.sub.3)--R.sub.3, --S(O)2--N(PRT)--R.sub.3, carbocycle, or heterocycle;
- R.sub.7 is alkyl, alkenyl, or alkynyl;
- each m1 is independently an integer from 0 to 3;
- and with the proviso that the compound, taken as a whole, contains 0 to 16 R.sub.6 groups, and that each E, G, T, and U, taken individually, contain 0 to 8 R.sub.6 groups.
Dependencies are inferred from the claim text.