Claims
- 1. A method for providing immunomodulation comprising administering to a human in need of such treatment a therapeutically effective amount of 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]tri(aryl-C.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=, --CH=, --NH(CH.sub.2)(CH.sub.2)N= and --NH(CH.sub.2)(CH.sub.2)(CH.sub.2)N=;
- 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=and --N=;
- 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, =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, =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= and --O--(CH.sub.2)2--N=;
- 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=;
- R.sup.20 and R.sup.20.degree. 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.degree. 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 ;
- (xii) --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)--,
- (iv) --(CH.sub.2).sub.m "O-- where m" is an integer between zero and six, inclusive,
- (v) --O(CH.sub.2).sub.m "-- 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) [[mono-- or dialkylamino]]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)NHO(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,
- (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 -thioalkoxy-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 the group consisting of pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, cytosinyl, thiocytosinyl. imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, xanthenyl, xanthonyl, xanthopterinyl, oxazoyl, oxazolidinyl, thiouracilyl, isoxazolyl, isoxazolidinyl, morpholinyl, indolyl, quinolinyl, uracilyl, urazolyl, uricyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, isoquinolinyl, thyminyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl and benzothienyl wherein any carbon or heteroatom with suitable valence may bear a substituent selected at each occurrence from R.sup.301,R.sup.302 and R.sup.303 independently as defined above.
- 2. A method according to claim 1 wherein R.sup.100 is hydrogen.
- 3. A method according to claim 1 wherein R.sup.101 is ethyl.
- 4. A method according to claim 1 wherein R.sup.102 is hydrogen.
- 5. A method according to claim 1 wherein R.sup.103 is hydroxy.
- 6. A method according to claim 1 wherein R.sup.104 is hydrogen.
- 7. A method according to claim 1 wherein R.sup.105 is a radical having the formula ##STR9## where X is --N=, and W, Y, Z, R.sup.1, R.sup.2, m, p and q are as defined therein.
- 8. A method according to claim 7 wherein W is --CH=.
- 9. A method according to claim 8 wherein Z is --(CH.sub.2).sub.3 --.
- 10. A method for providing immunomodulation comprising administering to a human in need of such treatment a therapeutically effective amount of a compound having 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 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =tert-butyldimethylsilyloxy; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (b) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; R.sup.1 =H; Z=(CH.sub.2)2; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (c) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)2; W=CH; X=--CH=; R.sup.2 =H; m=2; p=0; q=0; and Y=NMe;
- (d) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =CH3; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (e) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; p=2; q=0; and Y=N(benzyl);
- (f) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (g) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=2; p=2; q=0; and Y=CH.sub.2 ;
- (h) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (i) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=NCH.sub.3 ;
- (j) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; p=1; q=0; and Y=N(benzyl);
- (k) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 and Y taken together=--N--CH.sub.2 CH.sub.2 --; m=2; and p=1;
- (k) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)2; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (l) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)1; W=CH; X=--CH=; R.sup.2 =H; m=2; p=0; q=0; and Y=NEt;
- (m) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.3 ; W=CH; X=--N=; R.sup.2 =H; m=0; p=2; q=1; and Y=O;
- (n) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=NH;
- (o) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=0; p=0; q=2; and CH.sub.2 ;
- (p) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=2; p=1; q=0; and Y=NEt;
- (q) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=0; p=0; q=0; and Y=CH.sub.2 ;
- (r) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=2; p=2; q=0; and Y=CH.sub.2 ;
- (s) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--NH--CH2CH2N=; R.sup.2 =H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (t) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--NH--CH2CH2N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (u) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--NH--CH2CH2N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (v) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =Me; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; p=2; q=0; and Y=NMe;
- (w) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =Me; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; p=1; q=0; and Y=NMe;
- (x) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =Et; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; q=0; and Y=NEt;
- (y) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =--CH2-(3-pyridyl); Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=NH;
- (z) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =--(CH2)2--OH; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (aa) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =--(CH2)2--NH2; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (bb) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =--(CH2)2--NH2; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (cc) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =--(CH2)2--NH2; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (dd) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =--(CH2)2--CO2H; Z=(CH.sub.2).sub.3 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (ee) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =CO2H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (ff) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)2; W=CH; X=--CO--N=; R.sup.2 =H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (gg) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)2; W=CH; X=--O--(CH2)2N=; R.sup.2 =H; m=1; p=1; q=0; and Y=CH.sub.2 ;
- (hh) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=N(acetyl);
- (ii) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=S;
- (jj) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; p=2; q=0; and Y=N--(CH2)3-NH-(t-butyloxycarbonyl);
- (kk) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 =H; m=1; p=2; q=0; and Y=N--(CH2)3--NH.sub.2 ;
- (ll) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH--NHBoc;
- (mm) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH--NH.sub.2 ;
- (nn) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.105 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (oo) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 and R.sub.103 taken together form a bond; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (pp) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =H; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (qq) R.sub.100 =H; R.sub.101 =propyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (rr) R.sub.100 =H; R.sub.101 =methyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (ss) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)1; W=N; X=--CH=; R.sup.2 =benzyl; m=2; p=0; q=1; and Y=O;
- (tt) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)1; W=N; X=--CH=; R.sup.2 =benzyl; m=3; p=0; q=1; and Y=O;
- (uu) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 and Y taken together are --(CH.sub.2)3--N--; m=1; p=1; and q=0 (exo isomer);
- (vv) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; X=--CH=; R.sup.2 and Y taken together are --(CH.sub.2)3--N--; m=1; p=1; and q=0 (endo isomer);
- (ww) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)0; W=CH; x=--CH=; 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 =OH; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =H; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (yy) R.sub.100 =F; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =H; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (zz) R.sub.100 =OC(O)CH.sub.3 ; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =H; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ; and
- (aaa) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
- 11. A method for providing immunomodulation comprising administering to a human in need of such treatment a therapeutically effective amount of a compound having the formula: ##STR12## 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 ##STR13## wherein (a) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =tert-butyldimethylsilyloxy; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (b) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (e) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.0 ; W=CH; X=--CH=; R.sup.2 =H; m=1; p=2; q=0; and Y=N(benzyl);
- (f) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.3 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- (i) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=NCH.sub.3 ;
- (m) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.3 ; W=CH; X=--N=; R.sup.2 =H; m=0; p=2; q=1; and Y=O;
- (n) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=NH;
- (o) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=0; p=0; q=2; and Y=CH.sub.2 ;
- (z) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; --(CH2)2--OH; Z=(CH.sub.2).sub.2 ; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=O;
- (mm) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.105 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ; and
- (zz) R.sub.100 =H; R.sub.101 =ethyl; R.sub.102 =H; R.sub.103 =OH; R.sub.104 =H; R.sup.1 =H; Z=(CH.sub.2)3; W=CH; X=--N=; R.sup.2 =H; m=1; p=2; q=0; and Y=CH.sub.2 ;
- or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
Parent Case Info
This application is a division of U.S. patent application Ser. No. 08/343,266, filed Nov. 21, 1994, which is a continuation of U.S. patent application Ser. No. 08/100,512, filed Jul. 30, 1993, which 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 (1)
Number |
Name |
Date |
Kind |
5457111 |
Luly et al. |
Oct 1995 |
|
Divisions (1)
|
Number |
Date |
Country |
Parent |
343266 |
Nov 1994 |
|
Continuations (1)
|
Number |
Date |
Country |
Parent |
100512 |
Jul 1993 |
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Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
32958 |
Mar 1993 |
|