Claims
- 1. A compound having the formula ##STR7## or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein:
- R.sup.100 is selected from the group consisting of hydrogen, hydroxy, halogen and --OR.sup.8 ;
- R.sup.101 is selected from the group consisting of methyl, ethyl, allyl and propyl;
- R.sup.102 is hydrogen and R.sup.103 is selected from the group consisting of (a) hydrogen,
- (b) hydroxy, and (c) hydroxy protected by a hydroxy-protecting group selected from tri(C.sub.1 -C.sub.8 -loweralkyl)silyl, C.sub.1 -C.sub.8 -loweralkyldiarylsilyl, triarylsilyl, tri(arylC.sub.1 -C.sub.12 -alkyl)silyl, triphenylmethyl-dimethylsilyl, trimethylsilylethoxycarbonyl, methylthiomethyoxyethoxycarbonyl, benzenesulfonylethoxycarbonyl, trimethylsilylethoxymethyl and aryl-C(O)-- or, taken together, R.sup.102 and R.sup.103 form a bond; and
- one of R.sup.104 and R.sup.105 is hydrogen, and the other of R.sup.104 and R.sup.105 is a radical having the formula ##STR8## where X is selected from the group consisting of --N.dbd., --CH.dbd., --NH(CH.sub.2)(CH.sub.2)N.dbd. and --NH(CH.sub.2)(CH.sub.2)(CH.sub.2)N.dbd.;
- m, p, and q are integers independently selected from the group consisting of zero, one, two and three, such that the sum (m+p+q) is between zero and six;
- W is selected from the group consisting of --CH.dbd. and --N.dbd.;
- Y is selected from the group consisting of oxygen; --S(O).sub.s -- where s is an integer selected from the group consisting of zero, one and two; --N(R.sup.8)-- and --C(R.sup.20)(R.sup.20')-- wherein R.sup.8, R.sup.20 and R.sup.20' are as defined below;
- Z is selected from the group consisting of --(CH.sub.2).sub.n -- and (C.sub.2 -to-C.sub.6 alkylidene) substituted with between one and three radicals independently selected from selected from the group consisting of --OR.sup.8, --S(O).sub.s R.sup.8, --S(O).sub.2 NR.sup.8 R.sup.8', --NR.sup.8 R.sup.8', --SO.sub.3 H, .dbd.NOR.sup.8, --R.sup.399 and --R.sup.400 wherein R.sup.8, R.sup.8', R.sup.399 and R.sup.400 are independently as defined below; and
- R.sup.1 and R.sup.2 are independently selected from the group consisting of (i) hydrogen; (ii) aryl substituted by R.sup.301, R.sup.302 and R.sup.303 wherein R.sup.301, R.sup.302 and R.sup.303 are as defined below; (iii) heterocyclic substituted by R.sup.301, R.sup.302 and R.sup.303 wherein R.sup.301, R.sup.302 and R.sup.303 are as defined below; and (iv) alkyl having j carbon atoms, where j is an integer between 1 and 10, substituted with between zero and 5 but no more than j radicals selected from the group consisting of --OR.sup.8, --S(O).sub.s R.sup.8 wherein s is independently defined as above, --S(O).sub.2 NR.sup.8 R.sup.8', --NR.sup.8 R.sup.8', --SO.sub.3 H, .dbd.NOR.sup.8, --R.sup.399 and --R.sup.400 wherein R.sup.8, R.sup.8', R.sup.399 and R.sup.400 are independently as defined below;
- or, taken together, Y and R.sup.2 form a trivalent radical selected from the group consisting of --(CH.sub.2).sub.3 --N.dbd. and --O--(CH.sub.2).sub.2 --N.dbd.;
- and where n is an integer between zero and five, inclusive, with the proviso that when Z is --(CH.sub.2).sub.n -- and n is one, X is --CH.dbd.;
- R.sup.20 and R.sup.20' are independently selected from the group consisting of hydrogen, hydroxy, hydroxy-C.sub.1 -C.sub.8 -alkyl, R.sup.402 --C(O)--N(R.sup.401)-C.sub.1 -C.sub.8 -alkyl wherein R.sup.401 and R.sup.402 are Independently selected from hydrogen, C.sub.1 -C.sub.8 -alkyl, aryl, aryl-C.sub.1 -C.sub.12 -alkyl and halosubstituted-C.sub.1 -C.sub.12 -alkyl and N,N-di-(C.sub.1 -C.sub.12 -alkyl)amino, or, taken together, R.sup.20 and R.sup.20' are selected from the group consisting of oxo, thiooxo and --O(CH.sub.2).sub.i O--, where i is selected from the group consisting of two, three and four;
- R.sup.399 is selected from the group consisting of
- (i) hydroxy;
- (ii) --C(O)OH;
- (iii) --C(O)OR.sup.8 wherein R.sup.8 is independently defined as below;
- (iv) --(C.sub.3 -to-C.sub.7 cycloalkyl);
- (v) oxo;
- (vi) thiooxo;
- (vii) epoxy;
- (viii) halogen;
- (ix) --CN;
- (x) --N.sub.3 ;
- (xi) --NO.sub.2 ;
- (xxi) --OR.sup.11' wherein R.sup.11' is independently defined as below;
- (xiii) --OR.sup.12' wherein R.sup.12' is independently defined as below;
- (xiv) --OR.sup.12" wherein R.sup.12" is independently defined as below; and
- (xv) guanidino substituted by a radical selected from the group consisting of hydrogen, C.sub.1 -C.sub.8 -loweralkyl, aryl, C.sub.1 -C.sub.12 -alkyl-C(O)-- or aryl-C(O)--, arylsulfonyl, C.sub.1 -C.sub.8 -alkoxycarbonyl, aryl-C.sub.1 -C.sub.12 -alkoxycarbonyl, aryloxycarbonyl and C.sub.1 -C.sub.12 -alkylsulfonyl;
- R.sup.400 is selected from the group consisting of
- (i) aryl substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (ii) --Q-aryl where aryl is substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (iii) heterocyclic substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (iv) --Q-heterocyclic where heterocyclic is substituted by R.sup.301, R.sup.302 and R.sup.303,
- (v) biaryl substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (vi) --Q-biaryl where biaryl is substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (vii) --aryl-Q-aryl' where aryl and aryl' are the same or different and are independently substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (viii) --aryl-Q-heterocyclic where heterocyclic and aryl are independently substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (ix) --heterocyclic-Q-aryl where heterocyclic and aryl are independently substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (x) --heterocyclic-aryl where heterocyclic and aryl are independently substituted by R.sup.301, R.sup.302 and R.sup.303 ; and
- (xi) --aryl-heterocyclic where heterocyclic and aryl are independently substituted by R.sup.301, R.sup.302 and R.sup.303 wherein R.sup.301, R.sup.302 and R.sup.303 are independently defined as below;
- --Q-- is selected from the group consisting of
- (i) --(C.sub.1 -to-C.sub.6 alkyl)--,
- (ii) --(C.sub.2 -to-C.sub.6 alkenyl)--,
- (iii) --(C.sub.2 -to-C.sub.6 alkynyl)--,
- (vi) --(CH.sub.2).sub.m" O-- where m" is an integer between zero and six, inclusive,
- (v) --O(CH.sub.2).sub.n" -- wherein m" is defined as above,
- (vi) --N(R.sup.8)C(O)-- wherein R.sup.8 is independently defined as below,
- (vii) --C(O)N(R.sup.8)-- wherein R.sup.8 is independently defined as below,
- (viii) --S(O).sub.s -- wherein s is independently defined as above,
- (ix) --N(R.sup.8)-- wherein R.sup.8 is independently defined as below,
- (x) --N(R.sup.8)S(O).sub.2 -- wherein R.sup.8 is independently defined as below,
- (xi) --S(O).sub.2 N(R.sup.8)-- wherein R.sup.8 is independently defined as below,
- (xii) --C(O)--,
- (xiii) --NN--,
- (xiv) --CHN--,
- (xv) --NCH--,
- (xvi) --ONCH--, and
- (xvii) --CHNO--;
- R.sup.8 and R.sup.8' are independently selected from the group consisting of
- (i) hydrogen;
- (ii) aryl substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (iii) heterocyclic substituted by R.sup.301, R.sup.302 and R.sup.303 ;
- (iv) --(C.sub.1 -to-C.sub.6 alkyl) substituted by R.sup.331, R.sup.332 and R.sup.333 ;
- (v) --(C.sub.3 -to-C.sub.6 alkenyl) substituted by R.sup.331, R.sup.332 and R.sup.333 ; and
- (vi) --(C.sub.3 -to-C.sub.6 alkynyl) substituted by R.sup.331, R.sup.332 and R.sup.333 wherein R.sup.301, R.sup.302, R.sup.303, R.sup.331, R.sup.332 and R.sup.333 are independently defined as below;
- R.sup.331, R.sup.332 and R.sup.333 are independently selected from the group consisting of
- (A) hydrogen,
- (A') halogen,
- (B) hydroxy,
- (C) C.sub.1 -C.sub.12 -alkylamino, di-(C.sub.1 -C.sub.12 -alkyl)amino, C.sub.3 -C.sub.8 -cycloalkylamino, di-(C.sub.3 -C.sub.8 -cycloalkyl)amino or (C.sub.3 -C.sub.8 -cycloalkyl)(C.sub.1 -C.sub.12 -alkyl)amino,
- (D) carboxyl,
- (E) carboxamido,
- (F) thiol,
- (G) C.sub.1 -C.sub.8 -alkylthioether,
- (H) C.sub.1 -C.sub.8 -alkylether,
- (I) guanidino,
- (J) C.sub.1 -C.sub.8 -alkoxycarbonyl,
- (K) aryl-C.sub.1 -C.sub.12 -alkoxycarbonyl,
- (L) C.sub.1 -C.sub.8 -alkoxycarbonylamino,
- (M) C.sub.1 -C.sub.12 -alkyl-C(O)--NH-- or aryl-C(O)--NH--,
- (N) aryl-C.sub.1 -C.sub.12 -alkoxycarbonylamino,
- (O) aryloxycarbonylamino,
- (P) acylguanidino wherein acyl is C.sub.1 -C.sub.12 -alkyl-C(O)-- or aryl-C(O)--,
- (Q) arylsulfonylguanidino,
- (R) C.sub.1 -C.sub.8 -alkoxycarbonylguanidino,
- (S) amino,
- (T) aryl-C.sub.1 -C.sub.12 -alkoxycarbonylguanidino,
- (U) aryloxycarbonylguanidino,
- (V) (C.sub.1 -C.sub.12 -alkyl)NHC(O)--,
- (X) (C.sub.1 -C.sub.12 -alkyl)(C.sub.1 -C.sub.12 -alkyl)NHC(O)--,
- (Y) N-arylcarboxamido,
- (z) N,N-diarylcarboxamido,
- (AA) OSO.sub.2 R.sup.11, where R.sup.11 is independently selected from the group consisting of C.sub.1 -C.sub.8 -loweralkyl, aryl-C.sub.1 -C.sub.12 -alkyl substituted by R.sup.301, R.sup.302 and R.sup.303, and aryl substituted by R.sup.301, R.sup.302 and R.sup.303 wherein R.sup.301, R.sup.302 and R.sup.303 are independently defined as below;
- (BB) oxo,
- (CC) epoxy,
- (DD) arylether,
- (EE) arylthioether,
- (FF) aryl-C.sub.1 -C.sub.12 -alkylether,
- (GG) aryl-C.sub.1 -C.sub.12 -alkylthioether,
- (HH) (heterocyclic)ether,
- (II) (heterocyclic)thioether,
- (JJ) (heterocylic)-C.sub.1 -C.sub.12 -alkylether,
- (KK) (heterocyclic)-C.sub.1 -C.sub.12 -alkylthioether,
- (LL) aryl,
- (MM) heterocyclic,
- (NN) --SO.sub.3 H,
- (OO) --S(O).sub.2 NR.sup.16' R.sup.16" wherein R.sup.16 and R.sup.16' are independently defined as below, and
- (PP) --S(O).sub.s R.sup.14',
- where each aryl and heterocyclic moiety is independently substituted by R.sup.301, R.sup.302 and R.sup.303,
- R.sup.14' is selected from the group consisting of hydrogen, C.sub.1 -C.sub.8 -loweralkyl, aryl-C.sub.1 -C.sub.12 -alkyl, C.sub.3 -C.sub.8 -cycloalkyl and C.sub.3 -C.sub.8 -cycloalkyl-C.sub.1 -C.sub.8 -alkyl, and
- R.sup.16' and R.sup.16" are independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.8 -loweralkyl, hydroxy-C.sub.1 -C.sub.8 -loweralkyl, carboxy-C.sub.1 -C.sub.8 -alkyl, C.sub.1 -C.sub.8 -thioloweralkyl, C.sub.1 -C.sub.8 -thioalkoxyl-C.sub.1 -C.sub.8 -alkyl, guanidino-C.sub.1 -C.sub.8 -alkyl, aminoalkyl of the formula (R.sup.403)(R.sup.404)N-C.sub.1 -C.sub.8 -alkyl wherein R.sup.403 and R.sup.404 are independently selected from hydrogen, C.sub.1 -C.sub.8 -alkyl, aryl and aryl-C.sub.1 -C.sub.12 -alkyl or R.sup.403 and R.sup.404, taken together, are --(CH.sub.2).sub.bb -- wherein bb is 2-6 and aryl-C.sub.1 -C.sub.12 -alkyl,
- or, when appended to a nitrogen atom, R.sup.8 and R.sup.8' and the nitrogen atom to which they are connected form a 3- to 7-membered heterocyclic ring;
- R.sup.301, R.sup.302 and R.sup.303 are independently selected from the group consisting of
- (i) hydrogen;
- (ii) --(C.sub.1 -to-C.sub.7 alkyl);
- (iii) --(C.sub.2 -to-C.sub.6 alkenyl);
- (iv) halogen;
- (v) --(CH.sub.2).sub.m NR.sup.8 R.sup.8' wherein m, R.sup.8 and R.sup.8' are independently defined as above where m is an integer between zero and six, inclusive;
- (vi) --CN;
- (vii) --CHO;
- (viii) mono-, di-, tri-, or perhalogenated-C.sub.1 -C.sub.12 -alkyl;
- (ix) --S(O).sub.s R.sup.8 wherein s and R.sup.8' are independently defined as above;
- (x) --C(O)NR.sup.8 R.sup.8' wherein R.sup.8 and R.sup.8' are independently defined as above;
- (xi) --(CH.sub.2).sub.m OR.sup.8 wherein m and R.sup.8 are independently defined as above;
- (xii) --CH(OR.sup.12')(OR.sup.12"), where R.sup.12' and R.sup.12" are independently --(C.sub.1 -to-C.sub.3 alkyl) or, taken together, form an ethylene or propylene bridge;
- (xiii) --(CH.sub.2).sub.m OC(O)R.sup.8 wherein m and R.sup.8 are independently defined as above;
- (xiv) --(CH.sub.2).sub.m C(O)OR.sup.8 wherein m and R.sup.8 are independently defined as above;
- (xv) --OR.sup.11', where R.sup.11' is selected from the group consisting of
- (A) --PO(OH)OH,
- (B) --SO.sub.3 H, and
- (C) --C(O)(CH.sub.2).sub.m C(O)OH wherein m is independently defined as above;
- (xvi) --S(O).sub.2 NR.sup.8 R.sup.8', where t is one or two and R.sup.8 and R.sup.8' are independently defined as above;
- (xvii) --NO.sub.2 ;
- (xviii) --N.sub.3 ; and
- (xviv) guanidino optionally substituted by a radical selected from the group consisting of C.sub.1 -C.sub.8 -loweralkyl, aryl, C.sub.1 -C.sub.12 -alkyl-C(O)-- or aryl-C(O)--, arylsulfonyl, C.sub.1 -C.sub.8 -alkoxycarbonyl, aryl-C.sub.1 -C.sub.12 -alkoxycarbonyl, aryloxycarbonyl and C.sub.1 -C.sub.12 -alkylsulfonyl,
- subject to the proviso that each of substituents R.sup.301, R.sup.302 and R.sup.303 may comprise no more than twenty non-hydrogen atoms;
- or, taken together, any two adjacent R.sup.301, R.sup.302 and R.sup.303 and the atoms to which they are attached may form a carbocyclic or heterocyclic ring;
- wherein at each occurrence aryl is independently selected from phenyl, 1-naphthyl, 2-naphthyl, fluorenyl, (1,2)-dihydronaphthyl, (1,2,3,4-)-tetrahydronaphthyl, indenyl and indanyl; and at each occurrence heterocyclic is independently selected from (I) an aromatic or non-aromatic 5-, 6- or 7-membered ring having one, two or three heteroatoms independently selected from oxygen, sulfur and nitrogen, (II) a bi- or tri-cyclic group comprising six-membered rings and having one, two or three heteroatoms independently selected from oxygen, sulfur and nitrogen or (III) a 5-membered or 7-membered ring heterocycle fused to a benzene ring; wherein in any heterocycle any of the nitrogen, sulfur and carbon atoms can be substituted with hydroxy, thiol, oxo or thioxo or any of the nitrogen atoms can be quaternized.
- 2. A compound according to claim 1 wherein R.sup.100 is hydrogen.
- 3. A compound according to claim 1 wherein R.sup.101 is ethyl.
- 4. A compound according to claim 1 wherein R.sup.102 is hydrogen.
- 5. A compound according to claim 1 wherein R.sup.103 is hydroxy.
- 6. A compound according to claim 1 wherein R.sup.104 is hydrogen.
- 7. A compound according to claim 1 wherein R.sup.105 is a radical having the formula ##STR9## where X is --N.dbd., and W, Y, Z, R.sup.1, R.sup.2, m, p and q are as defined therein.
- 8. A compound according to claim 7 wherein W is --CH.dbd..
- 9. A compound according to claim 8 wherein Z is --(CH.sub.2).sub.3 --.
- 10. A compound of the formula ##STR10## wherein one of R.sup.104 and R.sup.105 is hydrogen, and the other of R.sup.104 and R.sup.105 is a radical having the formula ##STR11## wherein (a) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.tert-butyldimethylsilyloxy; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (b) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)2; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (c) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=2; p=0; q=0; and Y.dbd.NMe;
- (d) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.CH3; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (e) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.N(benzyl);
- (f) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (g) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=2; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (h) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (i) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.NCH.sub.3 ;
- (j) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.N(benzyl);
- (k) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 and Y taken together=--N--CH.sub.2 CH.sub.2 --; m=2; and p=1;
- (k) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (l) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)1; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=2; p=0; q=0; and Y.dbd.NEt;
- (m) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.3 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=0; p=2; q=1; and Y.dbd.O;
- (n) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.NH;
- (o) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=0; p=0; q=2; and Y.dbd.CH.sub.2 ;
- (p) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=2; p=1; q=0; and Y.dbd.NEt;
- (q) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=0; p=0; q=0; and Y.dbd.CH.sub.2 ;
- (r) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=2; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (s) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--NH--CH2CH2N.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (t) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--NH--CH2CH2N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (u) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--NH--CH2CH2N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (v) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.Me; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.NMe;
- (w) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.Me; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.NMe;
- (x) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.Et; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.NEt;
- (y) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--CH2-(3-pyridyl); Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.NH;
- (z) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--(CH2)2--OH; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (aa) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--(CH2)2--NH2; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (bb) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--(CH2)2--NH2; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (cc) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--(CH2)2--NH2; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (dd) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--CH2--CO2H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (ee) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--H.dbd.; R.sup.2 .dbd.--CO2H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (ff) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--CO--N.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (gg) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--O--(CH2)2N.dbd.; R.sup.2 .dbd.H; m=1; p=1; q=0; and Y.dbd.CH.sub.2 ;
- (hh) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.N(acetyl);
- (ii) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.S;
- (jj) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.N--(CH2)3--NH-(t-butyloxycarbonyl);
- (kk) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.N--(CH2)3--NH.sub.2 ;
- (ll) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH--NHBoc;
- (mm) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH--NH.sub.2 ;
- (nn) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.105 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (oo) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 and R.sub.103 taken together form a bond; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (pp) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.H; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (qq) R.sub.100 .dbd.H; R.sub.101 .dbd.propyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (rr) R.sub.100 .dbd.H; R.sub.101 .dbd.methyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (ss) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)1; W.dbd.N; X.dbd.--CH.dbd.; R.sup.2 .dbd.benzyl; m=2; p=0; q=1; and Y.dbd.O;
- (tt) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)1; W.dbd.N; X.dbd.--CH.dbd.; R.sup.2 .dbd.benzyl; m=3; p=0; q=1; and Y.dbd.O;
- (uu) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 and Y taken together are --(CH.sub.2).sub.3 --N--; m=1; p=1; and q=0 (exo isomer);
- (vv) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 and Y taken together are --(CH.sub.2).sub.2 --N--; m=1; p=1; and q=0 (endo isomer);
- (ww) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 and Y taken together are --O--(CH.sub.2).sub.2 --N--; m=1; p=2; and q=0 (endo isomer);
- (xx) R.sub.100 .dbd.OH; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.H; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (yy) R.sub.100 .dbd.F; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.H; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (zz) R.sub.100 .dbd.OC(O)CH.sub.3 ; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.H; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ; and
- (aaa) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
- 11. A compound of the formula ##STR12## wherein one, of R.sup.104 and R.sub.105 is hydrogen, and the other of R.sub.104 and R.sub.105 is a radical having the formula ##STR13## wherein (a) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.tert-butyldimethylsilyloxy; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (b) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)2; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (e) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)0; W.dbd.CH; X.dbd.--CH.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.N(benzyl);
- (f) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ;
- (l) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.NCH.sub.3 ;
- (m) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.3 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=0; p=2; q=1; and Y.dbd.O;
- (n) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.NH;
- (o) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2).sub.2; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=0; p=0; q=2; and Y.dbd.CH.sub.2 ;
- (z) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.--(CH2)2--OH; Z.dbd.(CH.sub.2).sub.2 ; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.O;
- (mm) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.105 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sub.2 .dbd.H; m=1; p=2; q=0; and Y.dbd.CH.sub.2 ; and
- (zz) R.sub.100 .dbd.H; R.sub.101 .dbd.ethyl; R.sub.102 .dbd.H; R.sub.103 .dbd.OH; R.sub.104 .dbd.H; R.sup.1 .dbd.H; Z.dbd.(CH.sub.2)3; W.dbd.CH; X.dbd.--N.dbd.; R.sup.2 .dbd.H; m=1; p=2; q.dbd.0; and Y.dbd.CH.sub.2 ;
- or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
Parent Case Info
This application is a continuation of U.S. patent application Ser. No. 08/100,512, filed Jul. 30, 1993, which abandoned is a continuation-in-part of the U.S. patent application Ser. No. 08/032,958, filed on Mar. 17, 1993, now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5250678 |
Goulet et al. |
Oct 1993 |
|
5262533 |
Sinclair et al. |
Nov 1993 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
428365 |
May 1991 |
EPX |
WO9220688 |
Nov 1992 |
WOX |
Continuations (1)
|
Number |
Date |
Country |
Parent |
100512 |
Jul 1993 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
32958 |
Mar 1993 |
|