US5502068A
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Cyclopropylpyrroloindole-oligopeptide anticancer agents
Assignee: University of Alberta
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Filing: 1995-01-31
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Granted: 1996-03-26
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Expires: 2015-01-31
Abstract
Abstract The invention is directed to novel cyclopropylpyrroloindole-oligopeptide compounds which are useful as anticancer agents. The novel cyclopropylpyrroloindole-oligopeptide compounds have the following general structure: <IMAGE> wherein, Het1 and Het2 are individually selected from the group consisting of pyrrole, imidazole, triazole, thiophene, furan, thiazole, oxazole and pyrazole, R is selected from the group consisting of a valence bond; a C1-C6 alkyl; a C2-C6 alkenyl; a C2-C6 alkynyl; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C1-C6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3.
Inventors
- 👤 J. William Lown
- 👤 Yuqiang Wang
- 👤 Weide Luo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 03:06
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/02; C07D487/10; A; A61; A61P; A61P35/00
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
138 words
Compounds of the formula: ##STR23## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, thiophene, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3.
Claim 2
Dependent Claim
138 words
Compounds of the formula: ##STR23## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, thiophene, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3.
Claim 3
Dependent Claim
25 words
The compounds according to claim 1, wherein R is selected from the group consisting of (CH 2 ) 1-6 --CH═CH--, E or Z; and --C.tbd.C--.
Claim 4
Dependent Claim
20 words
The compound according to claim 1, wherein said aromatic group is selected from the group consisting of phenyl and naphthyl.
Claim 5
Dependent Claim
24 words
The compounds according to claim 1, wherein R is a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7.
Claim 6
Dependent Claim
24 words
The compounds according to claim 1, wherein Het 1 and Het 2 are both N-alkylpyrrole, wherein the alkyl contains 1 to 4 carbon atoms.
Claim 7
Dependent Claim
24 words
The compounds according to claim 1, wherein Het 1 and Het 2 are both N-alkoxymethylpyrrole, wherein the alkoxy contains 1 to 4 carbon atoms.
Claim 8
Dependent Claim
24 words
The compounds according to claim 1, wherein Het 1 and Het 2 are both N-alkylimidazole, wherein the alkyl contains 1 to 4 carbon atoms.
Claim 9
Dependent Claim
24 words
The compounds according to claim 1, wherein Het 1 and Het 2 are both N-alkoxymethylimidazole, wherein the alkoxy contains 1 to 4 carbon atoms.
Claim 10
Dependent Claim
39 words
The compounds according to claim 1, wherein Het 1 and Het 2 are individually selected from the group consisting of thiophene, furan, thiazole, oxazole, N-alkylpyrrole, imidazole, pyrazole and triazole, wherein said alkyl group contains 1 to 4 carbon atoms.
Claim 11
Dependent Claim
39 words
The compounds according to claim 1, wherein Het 1 and Het 2 are individually selected from the group consisting of thiophene, furan, thiazole, oxazole, N-alkoxymethylpyrrole, imidazole, pyrazole, and triazole, wherein said alkoxy group contains 1 to 4 carbon atoms.
Claim 12
Dependent Claim
20 words
The compounds according to claim 1, wherein A is a straight chain alkyl group of 1 to 6 carbon atoms.
Claim 13
Dependent Claim
53 words
The compounds according to claim 1, wherein A is an amidine, with an aliphatic chain, of the formula ##STR24## wherein r is 0 to 5 and X is selected from the group consisting of --H, --OH, --NH 2 , --CH 3 , --CH 2 CH 3 , and C 3 H 7 .
Claim 14
Dependent Claim
25 words
The compounds according to claim 1, wherein A is an amidine, wherein at least one nitrogen atom is a member of a five-membered heterocyclic structure.
Claim 15
Dependent Claim
45 words
The compounds according to claim 1, wherein A is a guanidine of formula ##STR25## wherein r=0 to 5 and X is selected from the group consisting of --H, --OH, --NH 2 , --CH 3 , C 2 H 5 and C 3 H 7 .
Claim 16
Dependent Claim
45 words
The compounds according to claim 1, wherein A is a quaternary, tertiary or secondary ammonium salt of the formula ##STR26## wherein r=0 to 5 and q is 0, 1, 2, 3, and X is an alkyl or alkenyl group of 1 to 3 carbon atoms.
Claim 17
Dependent Claim
38 words
The compounds according to claim 1, wherein A is a sulfonium salt of formula CrH 2r --SXY, wherein r is 0 to 5 and X and Y are alkyl or alkenyl groups of 1 to 3 carbon atoms.
Claim 18
Dependent Claim
150 words
A pharmaceutical composition comprising a compound of the formula: ##STR27## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, triazole, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3, in combination with a pharmaceutically acceptable carrier.
Claim 19
Dependent Claim
150 words
A pharmaceutical composition comprising a compound of the formula: ##STR27## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, triazole, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3, in combination with a pharmaceutically acceptable carrier.
Claim 20
Independent Claim
167 words
A method for alkylating specific DNA sequences in vivo, comprising administering to a patient in need of such alkylating, an amount of a compound of the formula: ##STR28## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, triazole, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3, effective to alkylate specific DNA sequences.
Claim 21
Independent Claim
167 words
A method for alkylating specific DNA sequences in vivo, comprising administering to a patient in need of such alkylating, an amount of a compound of the formula: ##STR28## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, triazole, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3, effective to alkylate specific DNA sequences.
Claim 22
Dependent Claim
14 words
The method according to claim 18, wherein said DNA sequences are oncogene DNA sequences.
Claim 23
Independent Claim
179 words
A method of treating solid and blood-borne cancers selected from the group consisting of nasopharyngeal tumors and lymphocytic leukemia comprising administering to a patient in need of such treatment, an amount of a compound of the formula: ##STR29## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, triazole, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3, effective to treat said solid and blood-borne cancers.
Claim 24
Independent Claim
179 words
A method of treating solid and blood-borne cancers selected from the group consisting of nasopharyngeal tumors and lymphocytic leukemia comprising administering to a patient in need of such treatment, an amount of a compound of the formula: ##STR29## wherein, Het 1 and Het 2 are individually selected from the group consisting of pyrrole, imidazole, N-alkylimidazole, N-alkoxymethylimidazole, triazole, thiophene, furan, thiazole, oxazole, N-alkylpyrrole, N-alkoxymethylpyrrole and pyrazole, R is selected from the group consisting of a valence bond; a divalent C 1 -C 6 alkyl; a divalent C 2 -C 6 alkenyl; a divalent C 2 -C 6 alkynyl; a divalent cycloalkane of formula C p H 2p-2 wherein p is 3 to 7; and an ortho, meta or para linked aromatic group, A is selected from the group consisting of a C 1 -C 6 alkyl group; an amidine or derivative thereof; a guanidine; a secondary, tertiary or quaternary ammonium salt; and a sulfonium salt, n is 0 to 3, and m is 0 to 3, wherein when n=0, m is 1-3, effective to treat said solid and blood-borne cancers.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-03-26 | 1999-09-25 | 2000-03-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-03-26 | 2003-09-25 | 2004-03-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-03-26 | 2007-09-25 | 2008-03-26 | $7700.00 | Window Closed / Lapsed |