US 5,475,110 AGranted

Fused Pyrrolocarbazoles

AssigneeCephalon, Inc.

InventorsRobert L. Hudkins, Ernest Knight, Jr.

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Abstract

Disclosed herein are compounds referred to as "fused pyrrolocarbazoles" which possess a variety of functional activities. The disclosed compounds are represented by the following general formula: ##STR1## Methodologies for the synthetic production of fused pyrrolocarbazoles are also disclosed, as well as exemplary uses of the compounds.

Claims18

Dependent claims

A fused pyrrolocarbazole represented by the following general formula:

##STR14## wherein:
a) R.sup.1 is selected from the group consisting of H, alkyl of 1-4 carbons aryl, arylalkyl, heteroaryl, heteroarylalkyl, COR.sup.9, where R.sup.9 is selected from the group consisting of alkyl of 1-4 carbons, and aryl;
--OR.sup.10, where R.sup.10 is selected from the group consisting of H and alkyl of 1-4 carbons;
--CONH.sub.2, --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n NR.sup.7 R.sup.8, where n is an integer selected from the group consisting of 1, 2, 3, and 4;
and --O(CH.sub.2).sub.n NR.sup.7 R.sup.8 wherein either
1) R.sup.7 and R.sup.8 independently are selected from the group consisting of H and alkyl of 1-4 carbons;
or
2) R.sup.7 and R.sup.8 are combined together to form a linking group of the general formula --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 --, where X.sup.1 is selected from the group consisting of O, S and CH.sub.2 ;
c) R.sup.2 is selected from the group consisting of H, --SO.sub.2 R.sup.9, --CO.sub.2 R.sup.9, COR.sup.9, alkyl of 1-8 carbons, alkenyl of 1-8 carbons, alkynyl of 1-8 carbons, and a monosaccharide of 5-7 carbons wherein each hydroxyl group of said monosaccharide is independently selected from the group consisting of unsubstituted hydroxyl group and a replacement moiety replacing said hydroxyl group, said replacement moiety selected from the group consisting of H, alkyl of 1-4 carbons, alkylcarbonyloxy of 2-5 carbons and alkoxy of 1-4 carbons;
wherein either
1 ) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is unsubstituted;
or
2) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is independently substituted with a moiety selected from the group consisting of 1-3 aryl of 6-10 carbons, heteroaryl, F, Cl, Br, I, --CN, --NO.sub.2, OH, --OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, O-tetrahydropyranyl, NH.sub.2, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CO.sub.2 R.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, --NHC(.dbd.NH)NH.sub.2, --NR.sup.10 SO.sub.2 R.sup.9, --S(O).sub.y R.sup.11, where R.sup.11 is selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl, wherein y is an integer selected from the group consisting of 1 and 2;
--SR.sup.11 , --CO.sub.2 R.sup.9, --CONR.sup.7 R.sup.8, --CHO, COR.sup.9, --CH.sub.2 OR.sup.7, --CH.dbd.NNR.sup.11 R.sup.12, --CH.dbd.NOR.sup.11, --CH.dbd.NR.sup.9, --CH.dbd.NNHC(N.dbd.NH)NH.sub.2, --SO.sub.2 NR.sup.12 R.sup.13 and --PO(OR.sup.11).sub.2 ;
and wherein either
i) R.sup.12 and R.sup.13 are each independently selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl;
or
ii) R.sup.12 and R.sup.13 are combined together to form a linking group of the general formula --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 ;
d) R.sup.3, R.sup.4, R.sup.5 and R.sup.6, are each independently selected from the group consisting of H, aryl, heteroaryl;
F, Cl, Br, I, --CN, CF.sub.3, --NO.sub.2, OH, --OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, NH.sub.2, --CH.sub.2 OH, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, --SR.sup.11, --S(O).sub.y R.sup.11 wherein y is an integer selected from the group consisting of 1 and 2;
--CO.sub.2 R.sup.9, --COR.sup.9, --CONR.sup.7 R.sup.8, --CHO, --CH.dbd.NOR.sup.11, --CH.dbd.NR.sup.9, --CH.dbd.NNR.sup.11 R.sup.12, --(CH.sub.2).sub.n SR.sup.9, wherein n is an integer selected from the group consisting of 1, 2, 3 and 4 --(CH.sub.2).sub.n S(O).sub.y R.sup.9, --CH.sub.2 SR.sup.14 where R.sup.14 is alkyl of 1-4 carbons;
--CH.sub.2 S(O).sub.y R.sup.14, --(CH.sub.2).sub.n NR.sup.7 R.sup.8, alkyl of 1-8 carbons;
preferably alkyl of 1-4 carbons;
alkenyl of 1-8 carbons, preferably alkenyl of 1-4 carbons;
alkynyl of 1-8 carbons, preferably alkynyl of 1-4 carbons;
wherein either
1) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is unsubstituted;
or
2) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is independently substituted with a moiety selected from the group consisting of 1-3 aryl of 6-10 carbons, heteroaryl, F, Cl, Br, I, --CN, --NO.sub.2, OH, --OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, O-tetrahydropyranyl, NH.sub.2, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CO.sub.2 R.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, --NHC(.dbd.NH)NH.sub.2, --NR.sup.10 SO.sub.2 R.sup.9, --S(O).sub.y R.sup.11, wherein R.sup.11 is selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl, wherein y is an integer selected from the group consisting of 1 and 2;
--SR.sup.11 , --CO.sub.2 R.sup.9, --CONR.sup.7 R.sup.8, -- CHO, COR.sup.9, --CH.sub.2 OR.sup.7, --CH.dbd.NNR.sup.11 R.sup.12, --CH.dbd.NOR.sup.11, --CH.dbd.NR.sup.9, --CH.dbd.NNHC(N.dbd.NH)NH.sub.2, --SO.sub.2 NR.sup.12 R.sup.13 and --PO(OR.sup.11).sub.2 ;
and wherein either
i) R.sup.12 and R.sup.13 are each independently selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl;
or
ii) R.sup.12 and R.sup.13 are combined together to form a linking group of the general formula --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 ;
d) X is selected from the group consisting of
1 ) an unsubstituted alkylene of 1-3 carbons;
or
2) an alkylene of 1-3 carbons substituted by R.sup.2, OR.sup.10, --SR.sup.10, R.sup.14, where R.sup.14 is an alkyl of 1-4 carbons;
phenyl, naphthyl, arylalkyl of 7-14 carbons;
or ##STR15## ##STR16## --CH.sub.2 Z--, --ZCH.sub.2 --, --CH.sub.2 ZCH.sub.2 --, where Z is selected from the group consisting of ##STR17## e) A.sup.1 and A.sup.2 are selected from the group consisting of H,H, H, --OR.sup.11, H, --SR.sup.11, H.sup.1 --N(R.sup.11).sub.2 ;
and a group wherein A.sup.1 and A.sup.2 together form a moiety selected from the group consisting of:
.dbd.O, .dbd.S;
and .dbd.NR.sup.11 ;
and
g) B.sup.1 and B.sup.2 are selected from the group consisting of H,H, H, --OR.sup.11, H, --SR.sup.11, H.sup.1 --N(R.sup.11).sub.2 ;
and a group wherein B.sup.1 and B.sup.2 together form a moiety selected from the group consisting of:
.dbd.O, .dbd.S;
and .dbd.NR.sup.11
with the proviso that at least one of the pairs A.sup.1, A.sup.2 or B.sup.1, B.sup.2 is .dbd.O.

46 more elements

Dependencies are inferred from the claim text.

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Abstract

A fused pyrrolocarbazole represented by the following general formula:

##STR14## wherein:
a) R.sup.1 is selected from the group consisting of H, alkyl of 1-4 carbons aryl, arylalkyl, heteroaryl, heteroarylalkyl, COR.sup.9, where R.sup.9 is selected from the group consisting of alkyl of 1-4 carbons, and aryl;
--OR.sup.10, where R.sup.10 is selected from the group consisting of H and alkyl of 1-4 carbons;
--CONH.sub.2, --NR.sup.7 R.sup.8, --(CH.sub.2).sub.n NR.sup.7 R.sup.8, where n is an integer selected from the group consisting of 1, 2, 3, and 4;
and --O(CH.sub.2).sub.n NR.sup.7 R.sup.8 wherein either
1) R.sup.7 and R.sup.8 independently are selected from the group consisting of H and alkyl of 1-4 carbons;
or
2) R.sup.7 and R.sup.8 are combined together to form a linking group of the general formula --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 --, where X.sup.1 is selected from the group consisting of O, S and CH.sub.2 ;
c) R.sup.2 is selected from the group consisting of H, --SO.sub.2 R.sup.9, --CO.sub.2 R.sup.9, COR.sup.9, alkyl of 1-8 carbons, alkenyl of 1-8 carbons, alkynyl of 1-8 carbons, and a monosaccharide of 5-7 carbons wherein each hydroxyl group of said monosaccharide is independently selected from the group consisting of unsubstituted hydroxyl group and a replacement moiety replacing said hydroxyl group, said replacement moiety selected from the group consisting of H, alkyl of 1-4 carbons, alkylcarbonyloxy of 2-5 carbons and alkoxy of 1-4 carbons;
wherein either
1 ) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is unsubstituted;
or
2) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is independently substituted with a moiety selected from the group consisting of 1-3 aryl of 6-10 carbons, heteroaryl, F, Cl, Br, I, --CN, --NO.sub.2, OH, --OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, O-tetrahydropyranyl, NH.sub.2, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CO.sub.2 R.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, --NHC(.dbd.NH)NH.sub.2, --NR.sup.10 SO.sub.2 R.sup.9, --S(O).sub.y R.sup.11, where R.sup.11 is selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl, wherein y is an integer selected from the group consisting of 1 and 2;
--SR.sup.11 , --CO.sub.2 R.sup.9, --CONR.sup.7 R.sup.8, --CHO, COR.sup.9, --CH.sub.2 OR.sup.7, --CH.dbd.NNR.sup.11 R.sup.12, --CH.dbd.NOR.sup.11, --CH.dbd.NR.sup.9, --CH.dbd.NNHC(N.dbd.NH)NH.sub.2, --SO.sub.2 NR.sup.12 R.sup.13 and --PO(OR.sup.11).sub.2 ;
and wherein either
i) R.sup.12 and R.sup.13 are each independently selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl;
or
ii) R.sup.12 and R.sup.13 are combined together to form a linking group of the general formula --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 ;
d) R.sup.3, R.sup.4, R.sup.5 and R.sup.6, are each independently selected from the group consisting of H, aryl, heteroaryl;
F, Cl, Br, I, --CN, CF.sub.3, --NO.sub.2, OH, --OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, NH.sub.2, --CH.sub.2 OH, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, --SR.sup.11, --S(O).sub.y R.sup.11 wherein y is an integer selected from the group consisting of 1 and 2;
--CO.sub.2 R.sup.9, --COR.sup.9, --CONR.sup.7 R.sup.8, --CHO, --CH.dbd.NOR.sup.11, --CH.dbd.NR.sup.9, --CH.dbd.NNR.sup.11 R.sup.12, --(CH.sub.2).sub.n SR.sup.9, wherein n is an integer selected from the group consisting of 1, 2, 3 and 4 --(CH.sub.2).sub.n S(O).sub.y R.sup.9, --CH.sub.2 SR.sup.14 where R.sup.14 is alkyl of 1-4 carbons;
--CH.sub.2 S(O).sub.y R.sup.14, --(CH.sub.2).sub.n NR.sup.7 R.sup.8, alkyl of 1-8 carbons;
preferably alkyl of 1-4 carbons;
alkenyl of 1-8 carbons, preferably alkenyl of 1-4 carbons;
alkynyl of 1-8 carbons, preferably alkynyl of 1-4 carbons;
wherein either
1) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is unsubstituted;
or
2) each alkyl of 1-8 carbons, alkenyl of 1-8 carbons, or alkynyl of 1-8 carbons is independently substituted with a moiety selected from the group consisting of 1-3 aryl of 6-10 carbons, heteroaryl, F, Cl, Br, I, --CN, --NO.sub.2, OH, --OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, O-tetrahydropyranyl, NH.sub.2, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CO.sub.2 R.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, --NHC(.dbd.NH)NH.sub.2, --NR.sup.10 SO.sub.2 R.sup.9, --S(O).sub.y R.sup.11, wherein R.sup.11 is selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl, wherein y is an integer selected from the group consisting of 1 and 2;
--SR.sup.11 , --CO.sub.2 R.sup.9, --CONR.sup.7 R.sup.8, -- CHO, COR.sup.9, --CH.sub.2 OR.sup.7, --CH.dbd.NNR.sup.11 R.sup.12, --CH.dbd.NOR.sup.11, --CH.dbd.NR.sup.9, --CH.dbd.NNHC(N.dbd.NH)NH.sub.2, --SO.sub.2 NR.sup.12 R.sup.13 and --PO(OR.sup.11).sub.2 ;
and wherein either
i) R.sup.12 and R.sup.13 are each independently selected from the group consisting of H, alkyl of 1-4 carbons, aryl of 6-10 carbons, and heteroaryl;
or
ii) R.sup.12 and R.sup.13 are combined together to form a linking group of the general formula --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 ;
d) X is selected from the group consisting of
1 ) an unsubstituted alkylene of 1-3 carbons;
or
2) an alkylene of 1-3 carbons substituted by R.sup.2, OR.sup.10, --SR.sup.10, R.sup.14, where R.sup.14 is an alkyl of 1-4 carbons;
phenyl, naphthyl, arylalkyl of 7-14 carbons;
or ##STR15## ##STR16## --CH.sub.2 Z--, --ZCH.sub.2 --, --CH.sub.2 ZCH.sub.2 --, where Z is selected from the group consisting of ##STR17## e) A.sup.1 and A.sup.2 are selected from the group consisting of H,H, H, --OR.sup.11, H, --SR.sup.11, H.sup.1 --N(R.sup.11).sub.2 ;
and a group wherein A.sup.1 and A.sup.2 together form a moiety selected from the group consisting of:
.dbd.O, .dbd.S;
and .dbd.NR.sup.11 ;
and
g) B.sup.1 and B.sup.2 are selected from the group consisting of H,H, H, --OR.sup.11, H, --SR.sup.11, H.sup.1 --N(R.sup.11).sub.2 ;
and a group wherein B.sup.1 and B.sup.2 together form a moiety selected from the group consisting of:
.dbd.O, .dbd.S;
and .dbd.NR.sup.11
with the proviso that at least one of the pairs A.sup.1, A.sup.2 or B.sup.1, B.sup.2 is .dbd.O.

46 more elements