CA2470515A1 - Dna minor groove binding compounds - Google Patents
Dna minor groove binding compounds Download PDFInfo
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- CA2470515A1 CA2470515A1 CA002470515A CA2470515A CA2470515A1 CA 2470515 A1 CA2470515 A1 CA 2470515A1 CA 002470515 A CA002470515 A CA 002470515A CA 2470515 A CA2470515 A CA 2470515A CA 2470515 A1 CA2470515 A1 CA 2470515A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
There is provided an oligopeptide compound comprising: (a) at least one nitrogen-containing basic group attached to at least one end of the oligopeptide; and (b) two or mor heterocyclic monomers, at least one of which is substituted in the heterocyclic part by a branched, cyclic or part cyclic C3-5 alkyl group, or a pharmaceutically acceptable salt or solvate thereof; which compound, salt or solvate binds to the minor groove of DNA.
Claims (43)
1. An oligopeptide compound comprising:
(a) at least one nitrogen-containing basic group attached to at least one end of the oligopeptide; and (b) two or more heterocyclic monomers, at least one of which is substituted in the heterocyclic part by a branched, cyclic or part cyclic C3-5 alkyl group, or a pharmaceutically acceptable salt or solvate thereof;
which compound, salt or solvate binds to the minor groove of DNA.
(a) at least one nitrogen-containing basic group attached to at least one end of the oligopeptide; and (b) two or more heterocyclic monomers, at least one of which is substituted in the heterocyclic part by a branched, cyclic or part cyclic C3-5 alkyl group, or a pharmaceutically acceptable salt or solvate thereof;
which compound, salt or solvate binds to the minor groove of DNA.
2. An oligopeptide compound comprising:
(a) at least one nitrogen-containing basic group attached to at least one end of the oligopeptide; and (b) two or more heterocyclic monomers, at least one of which is substituted on a ring C-atom in the heterocyclic part by a branched, cyclic or part cyclic C3-5 alkyl group, or a pharmaceutically acceptable salt or solvate thereof;
which compound, salt or solvate binds to the minor groove of DNA.
(a) at least one nitrogen-containing basic group attached to at least one end of the oligopeptide; and (b) two or more heterocyclic monomers, at least one of which is substituted on a ring C-atom in the heterocyclic part by a branched, cyclic or part cyclic C3-5 alkyl group, or a pharmaceutically acceptable salt or solvate thereof;
which compound, salt or solvate binds to the minor groove of DNA.
3. A compound as claimed in Claim 1 or Claim 2, wherein the nitrogen-containing basic group, in its neutral state, has a pK a in water of at least
4.
4. A compound as claimed in Claim 3, wherein the nitrogen-containing basic group is an amidino, guanidino or amino group, any of which may be cyclic or acyclic.
4. A compound as claimed in Claim 3, wherein the nitrogen-containing basic group is an amidino, guanidino or amino group, any of which may be cyclic or acyclic.
5. A compound as claimed in any one of the preceding claims, wherein each heterocyclic group is a 4- to 12-membered heterocyclic group containing one or more heteroatoms selected from N, O and S.
6. A compound as claimed in Claim 5, wherein each heterocyclic group is independently aromatic or part-aromatic.
7. A compound as claimed in Claim 6, wherein each heterocyclic group that is present is independently selected from the group consisting of pyrrolyl, imidazolyl, thiazolyl, oxazolyl, benzoxazolyl, furanyl, thienyl, pyridyl and coumarinyl.
8. A compound as claimed in Claim 7, wherein at least one heterocyclic group that is present is a thiazolyl group.
9. A compound as claimed in Claim 8, wherein the thiazolyl group is a 1,3-thiazolyl group that is substituted in the 5-position by, as appropriate, the branched, cyclic or part cyclic C3-5 alkyl group.
10. A compound as claimed in any one of the preceding claims, wherein the branched, cyclic or part cyclic C3-5 alkyl group is isopropyl.
11. A compound as claimed in any one of the preceding claims, which has a molecular weight of below 2000 g mol-1.
12. A compound as claimed in any one of the preceding claims, which is bioavailable.
13. A compound as claimed in any one of the preceding claims, which has a high affinity for DNA sequences.
14. A compound as claimed in Claim 12 that binds to the minor groove of a DNA oligomer or polymer with a dissociation constant of less than 10-5 M.
15. A compound as claimed in Claim l, wherein each essential branched, cyclic or part cyclic C3-5 alkyl substituent on a heterocyclic monomer is other than cyclopropyl.
16. A compound of formula I, wherein Rl represents Hetl, RIaC(O)- or D-A-N(H)-[Q]n- C(O)-E-C(O)-;
Rla represents H, aryl (which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy), aromatic or part-aromatic C13-14 tricyclic carbocyclyl (which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and Cl-4 alkoxy, and which latter group, if part-aromatic, is optionally substituted in the non-aromatic part by one or two oxo groups) or C1-12 alkyl (which latter group is optionally substituted and/or terminated by one or more substituents selected from halo and aryl (which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy));
A represents, at each occurrence when used herein, C2-6 alkylene or Al-C(O)N(H)-A2, wherein A2 is attached to the group D;
A1 represents C1-4 alkylene;
A2 represents C2-5 alkylene;
D represents, at each occurrence when used herein, -N(R2a)R2b, -C (=NR2c)N(R2d)R2e or -N(R2f)C(=NR2g)N(H)R2h;
R2a and R2b independently represent H, C1-6 alkyl, Het2 or R2a and R2b together represent (CH2)3-6, which alkylene group is optionally interrupted by NR4 and/or is optionally substituted by one or more C1-4 alkyl groups;
R4 represents H, Cl-6 alkyl or Het3;
R2c to R2h independently represent H or Cl-6 alkyl;
E represents -E1-Het4-, E2a, -(CH2)0-3N(H)C(O)-E2b-C(O)N(H)(CH2)0-3- or a structural fragment of the formula wherein E3 represents (CH2)1-2, CH=CH, CH=N, CH2-N(Ra), (CH2)0-1C(O), (CH2)0-1O or (CH2)0-1S;
Ra represents H or Cl-6 alkyl;
El represents (CH2)0-2 or CH=CH;
E2a and E2b independently represent C2-4 alkenylene, C3-6 cycloalkylene, phenylene or naphthylene;
Hetl to Het4 independently represent four- to twelve-membered heterocyclic groups containing one or more heteroatoms selected from N, O and S, which heterocyclic groups are optionally substituted by one or more substituents selected from =O, OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy;
R3a and R3b independently represent, at each occurrence when used herein, H or C1-4 alkyl, or R3a represents -C(O)R5;
R5 represents H or C1-4 alkyl;
n represents, at each occurrence when used herein, 2, 3, 4 or 5;
each individual Q independently represents a structural fragment of formula Ia, Ib, Ic, Id, Ie or If wherein R6 represents H or C1-6 alkyl;
R7 represents C1-12 alkyl;
R8, R9, R10 and R11 independently represent H or C1-12 alkyl;
G represents CH or N;
L represents O or S;
p,q and r independently represent 0, 1, 2 or 3; and provided that the compound comprises at least one structural fragment of formula Ib, Ic, Id, Ie or If in which R6 or R7, R8, R9, R10 or R11, respectively, represents branched, cyclic or part cyclic C3-5 alkyl;
or a pharmaceutically acceptable derivative thereof.
Rla represents H, aryl (which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy), aromatic or part-aromatic C13-14 tricyclic carbocyclyl (which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and Cl-4 alkoxy, and which latter group, if part-aromatic, is optionally substituted in the non-aromatic part by one or two oxo groups) or C1-12 alkyl (which latter group is optionally substituted and/or terminated by one or more substituents selected from halo and aryl (which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy));
A represents, at each occurrence when used herein, C2-6 alkylene or Al-C(O)N(H)-A2, wherein A2 is attached to the group D;
A1 represents C1-4 alkylene;
A2 represents C2-5 alkylene;
D represents, at each occurrence when used herein, -N(R2a)R2b, -C (=NR2c)N(R2d)R2e or -N(R2f)C(=NR2g)N(H)R2h;
R2a and R2b independently represent H, C1-6 alkyl, Het2 or R2a and R2b together represent (CH2)3-6, which alkylene group is optionally interrupted by NR4 and/or is optionally substituted by one or more C1-4 alkyl groups;
R4 represents H, Cl-6 alkyl or Het3;
R2c to R2h independently represent H or Cl-6 alkyl;
E represents -E1-Het4-, E2a, -(CH2)0-3N(H)C(O)-E2b-C(O)N(H)(CH2)0-3- or a structural fragment of the formula wherein E3 represents (CH2)1-2, CH=CH, CH=N, CH2-N(Ra), (CH2)0-1C(O), (CH2)0-1O or (CH2)0-1S;
Ra represents H or Cl-6 alkyl;
El represents (CH2)0-2 or CH=CH;
E2a and E2b independently represent C2-4 alkenylene, C3-6 cycloalkylene, phenylene or naphthylene;
Hetl to Het4 independently represent four- to twelve-membered heterocyclic groups containing one or more heteroatoms selected from N, O and S, which heterocyclic groups are optionally substituted by one or more substituents selected from =O, OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy;
R3a and R3b independently represent, at each occurrence when used herein, H or C1-4 alkyl, or R3a represents -C(O)R5;
R5 represents H or C1-4 alkyl;
n represents, at each occurrence when used herein, 2, 3, 4 or 5;
each individual Q independently represents a structural fragment of formula Ia, Ib, Ic, Id, Ie or If wherein R6 represents H or C1-6 alkyl;
R7 represents C1-12 alkyl;
R8, R9, R10 and R11 independently represent H or C1-12 alkyl;
G represents CH or N;
L represents O or S;
p,q and r independently represent 0, 1, 2 or 3; and provided that the compound comprises at least one structural fragment of formula Ib, Ic, Id, Ie or If in which R6 or R7, R8, R9, R10 or R11, respectively, represents branched, cyclic or part cyclic C3-5 alkyl;
or a pharmaceutically acceptable derivative thereof.
17. A compound as claimed in Claim 16, wherein:
R1a represents H or C1-12 alkyl, which latter group is optionally substituted and/or terminated by one or more substituents selected from halo and aryl, which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy; and the compound comprises at least one structural fragment of formula Ib, Ic, Id, Ie or If in which R7, R8, R9, R10 or R11, respectively, represents branched, cyclic or part cyclic C3-5 alkyl.
R1a represents H or C1-12 alkyl, which latter group is optionally substituted and/or terminated by one or more substituents selected from halo and aryl, which latter group is optionally substituted by one or more substituents selected from OH, halo, cyano, nitro, N(R3a)R3b, C1-4 alkyl and C1-4 alkoxy; and the compound comprises at least one structural fragment of formula Ib, Ic, Id, Ie or If in which R7, R8, R9, R10 or R11, respectively, represents branched, cyclic or part cyclic C3-5 alkyl.
18. A compound as claimed in Claim 16 or Claim 17, wherein aryl is phenyl or naphthyl.
19. A compound as claimed in any one of Claims 16 to 18, wherein alkyl and alkoxy groups are, where appropriate:
(a) straight-chain;
(b) branched-chain and/or cyclic; or (c) part cyclic/acyclic.
(a) straight-chain;
(b) branched-chain and/or cyclic; or (c) part cyclic/acyclic.
20. A compound as claimed in any one of Claims 16 to 19, wherein alkyl and alkoxy groups are, where appropriate:
(a) saturated or unsaturated;
(b) interrupted by one or more oxygen and/or sulfur atoms; and/or (c) unless otherwise specified, substituted by one or more halo atoms.
(a) saturated or unsaturated;
(b) interrupted by one or more oxygen and/or sulfur atoms; and/or (c) unless otherwise specified, substituted by one or more halo atoms.
21. A compound as claimed in any one of Claims 16 to 20, which is a compound of formula II, wherein Rl represents Het1, R1aC(O)- or D-A-N(H)-Q3-Q2-Q1-C(O)-E-C(O)-;
Q1 is absent or represents a structural fragment of formula Ia, Ib, Ic, Id, Ie or If;
Q2 represents a structural fragment of formula Ib, Ie or If;
Q3 represents a structural fragment of formula Ib, Id, Ie or If; and Hetl, Rla, D, A, E, R2a, R2b, A and the structural fragments of formulae Ia, Ib, Ic, Id, Ie and If are as defined in any one of Claims 16 to 20;
provided that:
(a) at least one of Ql, Q2 and Q3 represents a structural fragment of formula Id, Ie or If; and (b) at least one of R6 or R7, R8, R9, R10 and R11 (whichever is/are present) represents branched, cyclic or part cyclic C3-5 alkyl, or a pharmaceutically acceptable derivative thereof.
Q1 is absent or represents a structural fragment of formula Ia, Ib, Ic, Id, Ie or If;
Q2 represents a structural fragment of formula Ib, Ie or If;
Q3 represents a structural fragment of formula Ib, Id, Ie or If; and Hetl, Rla, D, A, E, R2a, R2b, A and the structural fragments of formulae Ia, Ib, Ic, Id, Ie and If are as defined in any one of Claims 16 to 20;
provided that:
(a) at least one of Ql, Q2 and Q3 represents a structural fragment of formula Id, Ie or If; and (b) at least one of R6 or R7, R8, R9, R10 and R11 (whichever is/are present) represents branched, cyclic or part cyclic C3-5 alkyl, or a pharmaceutically acceptable derivative thereof.
22. A compound as claimed in any one of Claims 16 to 21, wherein the compound comprises:
(a) at least one structural fragment of formula Ib in which G represents N
and R6 represents branched, cyclic or part cyclic C3-5 alkyl;
(b) at least one structural fragment of formula Id in which p represents 0 and R9 represents branched, cyclic or part cyclic C3-5 alkyl; and/or (c) at least one structural fragment of formula Ie in which q represents 0 and R10 represents branched, cyclic or part cyclic C3-5 alkyl.
(a) at least one structural fragment of formula Ib in which G represents N
and R6 represents branched, cyclic or part cyclic C3-5 alkyl;
(b) at least one structural fragment of formula Id in which p represents 0 and R9 represents branched, cyclic or part cyclic C3-5 alkyl; and/or (c) at least one structural fragment of formula Ie in which q represents 0 and R10 represents branched, cyclic or part cyclic C3-5 alkyl.
23. A compound as claimed in any one of Claims 16 to 23, wherein each of the at least one branched, cyclic or part cyclic C3-5 alkyl groups independently represents isopropyl, cyclopropylmethyl, isopentyl or cyclopentyl.
24. A compound as claimed in any one of Claims 16 to 21, wherein the compound comprises at least one structural fragment of formula Ib, Ic, Id, Ie or If in which R7, R8, R9, R10 or R11, respectively, represents isopropyl.
25. A compound as claimed in any one of Claims 16 to 24, which compound comprises at least one structural fragment of the formula
26. A compound as claimed in Claim 16, which compound is selected from the following:
(i) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1-H pyrrol-3-yl]-4-[(3,3-dimethylbutanoyl)amino]-1-methyl-1H pyrrole-2-carboxamide;
(ii) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(iii)N [3-(Dimethylamino)propyl]-2-({[4-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}amino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(iv) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-isopropyl-1H
pyrrol-3-yl]-4-({[4-(formylamino)-1-isopropyl-1H pyrrol-2-yl] carbonyl} -amino)-1-isopropyl-1H pyrrole-2-carboxamide (v) N [5-({[5-({[3-(Dimethylamino)propyl]amino]carbonyl)-1-isopentyl-1H pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-(formyl-amino)-1-isopentyl-1H pyrrole-2-carboxamide;
(vi) N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-isopropyl-1H pyrrol-3-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-4-(formyl-amino)-1-isopropyl-1H pyrrole-2-carboxamide;
(vii) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-2-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(viii) 4-({[4-(Formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}amino)-1-iso-propyl-N [1-methyl-5-({[3-(4-morpholinyl)propyl]amino}carbonyl)-1H
pyrrol-3-yl]-1H pyrrole-2-carboxamide;
(ix) 4-(Formylamino)-N [1-isopropyl-5-({[1-methyl-5-({[3-(1-pyrrolidinyl)-propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(x) N-[5-({[5-({[3-(Dimethylamino)propyl]amino{carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(xi) 2-(Acetylamino)-N-[5-({[5-({[3-(dimethylamino)propyl]amino)-carbonyl)-1,-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-5-isopropyl-1,3-thiazole-4-carboxamide;
(xii) 2-(Acetylamino)-N-[5-({[4-({[3-(dimethylamino)propyl]amino}-carbonyl)-5-isopropyl-1,3-thiazol-2-yl] amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-5-isopropyl-1,3-thiazole-4-carboxamide;
(xiii) 2-(Acetylamino)-N-(5-{[[(3-{[3-(dimethylamino)propyl]amino}-3-oxo-propyl)amino]carbonyl}-1-methyl-1H pyrrol-3-yl)-5-isopropyl-1,3-thiazole-4-carboxamide;
(xiv) N1,N3-Bis(2-{[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-amino}-2-oxoethyl)isophthalamide;
(xv) N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1H-pyrrol-3-yl]-4-(acetylamino)-1-methyl-1H-pyrrole-2-carboxamide;
(xvi) N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H-pyrrol-3-yl]-4-(acetyl-amino)-1-methyl-1H-pyrrole-2-carboxamide;
(xvii) N2,N5-Bis[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-1H
indole-2, 5-dicarboxamide;
(xviii) N2,N5-Bis[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]-amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-1H-indole-2, 5-dicarboxamide;
(xix) N2,N5-Bis[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H-pyrrol-3-yl]-1H-indole-2,5-dicarboxamide;
(xx) N2,N5-Bis[1-isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl)-propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]-1H-indole-2,5-dicarboxamide;
(xxi) 2-({[4-({[4-(Acetylamino)-1-methyl-1H-imidazol-2-yl]carbonyl}-amino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-N-[3-(dimethylamino)-propyl]-5-isopropyl-1,3-thiazole-4-carboxamide;
(xxii) 4-(Acetylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl) propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]-1-methyl-1H-pyrrole-2-carboxamide;
(xxiii) N-[1-Isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl)-propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-4-[(3-methoxybenzoyl)amino]-1-methyl-1H-pyrrole-2-carboxamide;
(xxiv) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-4-({[5-(formylamino)-2-methyl-3-thienyl]carbonyl}amino)-1-isopentyl-1H pyrrole-2-carboxamide;
(xxv) N-[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-5-isopropyl-2-[(3-methoxybenzoyl)amino]-1,3-thiazole-4-carboxamide;
(xxvi) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-4-{[(5-{[(9,10-dioxo-9,10-dihydro-2-anthracenyl)carbonyl]-amino]-2-methyl-3-thienyl)carbonyl]amino}-1-isopentyl-1H pyrrole-2-carboxamide;
(xxvii) N-[1-(Cyclopropylmethyl)-5-({[5-({[3-(dimethylamino)propyl]-amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino }carbonyl)-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(xxviii) 1-Cyclopentyl-N-[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-4-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]-carbonyl}-amino)-1H pyrrole-2-carboxamide;
(xxix) N2,N7-Bis[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3 -thiazol-2-yl] amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-9,10-dihydro-2,7-phenanthrenedicarboxamide;
(xxx) 4-(Formylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl)propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H
pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(xxxi) 4-(Acetylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H
pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(xxxii) 4-(Formylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H
pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(xxxiii)N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-[(3-methoxybenzoyl)amino]-1-methyl-1H pyrrole-2-carboxamide; and (xxxiv) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-{[(4-methoxyphenyl)acetyl] amino}-1-methyl-1H pyrrole-2-carboxamide.
(i) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1-H pyrrol-3-yl]-4-[(3,3-dimethylbutanoyl)amino]-1-methyl-1H pyrrole-2-carboxamide;
(ii) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(iii)N [3-(Dimethylamino)propyl]-2-({[4-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}amino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(iv) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-isopropyl-1H
pyrrol-3-yl]-4-({[4-(formylamino)-1-isopropyl-1H pyrrol-2-yl] carbonyl} -amino)-1-isopropyl-1H pyrrole-2-carboxamide (v) N [5-({[5-({[3-(Dimethylamino)propyl]amino]carbonyl)-1-isopentyl-1H pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-(formyl-amino)-1-isopentyl-1H pyrrole-2-carboxamide;
(vi) N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-isopropyl-1H pyrrol-3-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-4-(formyl-amino)-1-isopropyl-1H pyrrole-2-carboxamide;
(vii) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-2-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(viii) 4-({[4-(Formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}amino)-1-iso-propyl-N [1-methyl-5-({[3-(4-morpholinyl)propyl]amino}carbonyl)-1H
pyrrol-3-yl]-1H pyrrole-2-carboxamide;
(ix) 4-(Formylamino)-N [1-isopropyl-5-({[1-methyl-5-({[3-(1-pyrrolidinyl)-propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(x) N-[5-({[5-({[3-(Dimethylamino)propyl]amino{carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(xi) 2-(Acetylamino)-N-[5-({[5-({[3-(dimethylamino)propyl]amino)-carbonyl)-1,-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-5-isopropyl-1,3-thiazole-4-carboxamide;
(xii) 2-(Acetylamino)-N-[5-({[4-({[3-(dimethylamino)propyl]amino}-carbonyl)-5-isopropyl-1,3-thiazol-2-yl] amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-5-isopropyl-1,3-thiazole-4-carboxamide;
(xiii) 2-(Acetylamino)-N-(5-{[[(3-{[3-(dimethylamino)propyl]amino}-3-oxo-propyl)amino]carbonyl}-1-methyl-1H pyrrol-3-yl)-5-isopropyl-1,3-thiazole-4-carboxamide;
(xiv) N1,N3-Bis(2-{[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-amino}-2-oxoethyl)isophthalamide;
(xv) N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1H-pyrrol-3-yl]-4-(acetylamino)-1-methyl-1H-pyrrole-2-carboxamide;
(xvi) N-[5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H-pyrrol-3-yl]-4-(acetyl-amino)-1-methyl-1H-pyrrole-2-carboxamide;
(xvii) N2,N5-Bis[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-1H
indole-2, 5-dicarboxamide;
(xviii) N2,N5-Bis[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]-amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-1H-indole-2, 5-dicarboxamide;
(xix) N2,N5-Bis[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H-pyrrol-3-yl]-1H-indole-2,5-dicarboxamide;
(xx) N2,N5-Bis[1-isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl)-propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]-1H-indole-2,5-dicarboxamide;
(xxi) 2-({[4-({[4-(Acetylamino)-1-methyl-1H-imidazol-2-yl]carbonyl}-amino)-1-methyl-1H-pyrrol-2-yl]carbonyl}amino)-N-[3-(dimethylamino)-propyl]-5-isopropyl-1,3-thiazole-4-carboxamide;
(xxii) 4-(Acetylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl) propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]-1-methyl-1H-pyrrole-2-carboxamide;
(xxiii) N-[1-Isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl)-propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-4-[(3-methoxybenzoyl)amino]-1-methyl-1H-pyrrole-2-carboxamide;
(xxiv) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-4-({[5-(formylamino)-2-methyl-3-thienyl]carbonyl}amino)-1-isopentyl-1H pyrrole-2-carboxamide;
(xxv) N-[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-5-isopropyl-2-[(3-methoxybenzoyl)amino]-1,3-thiazole-4-carboxamide;
(xxvi) N-[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-4-{[(5-{[(9,10-dioxo-9,10-dihydro-2-anthracenyl)carbonyl]-amino]-2-methyl-3-thienyl)carbonyl]amino}-1-isopentyl-1H pyrrole-2-carboxamide;
(xxvii) N-[1-(Cyclopropylmethyl)-5-({[5-({[3-(dimethylamino)propyl]-amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino }carbonyl)-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(xxviii) 1-Cyclopentyl-N-[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-4-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]-carbonyl}-amino)-1H pyrrole-2-carboxamide;
(xxix) N2,N7-Bis[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3 -thiazol-2-yl] amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-9,10-dihydro-2,7-phenanthrenedicarboxamide;
(xxx) 4-(Formylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-methyl-1-piperazinyl)propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H
pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(xxxi) 4-(Acetylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H
pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(xxxii) 4-(Formylamino)-N-[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H
pyrrol-3-yl]-1-methyl-1H pyrrole-2-carboxamide;
(xxxiii)N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-[(3-methoxybenzoyl)amino]-1-methyl-1H pyrrole-2-carboxamide; and (xxxiv) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-{[(4-methoxyphenyl)acetyl] amino}-1-methyl-1H pyrrole-2-carboxamide.
27. A compound as claimed in Claim 26 which is:
(a) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(b) N [3-(Dimethylamino)propyl]-2-({[4-({[4-(formylamino)-1-methyl-1H
pyrrol-2-yl]carbonyl}amino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(c) N [5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-2-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(d) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(e) N2,N5-Bis[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]-amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-1H
indole-2,5-dicarboxamide;
(f) N [1-(Cyclopropylmethyl)-5-({[5-({[3-(dimethylamino)propyl]-amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide; or (g) N2,N7-Bis[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-9,10-dihydro-2,7-phenanthrenedicarboxamide.
(a) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopropyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(b) N [3-(Dimethylamino)propyl]-2-({[4-({[4-(formylamino)-1-methyl-1H
pyrrol-2-yl]carbonyl}amino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(c) N [5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]-2-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-5-isopropyl-1,3-thiazole-4-carboxamide;
(d) N [5-({[5-({[3-(Dimethylamino)propyl]amino}carbonyl)-1-methyl-1H
pyrrol-3-yl]amino}carbonyl)-1-isopentyl-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide;
(e) N2,N5-Bis[1-isopentyl-5-({[1-methyl-5-({[3-(4-morpholinyl)propyl]-amino}carbonyl)-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-1H
indole-2,5-dicarboxamide;
(f) N [1-(Cyclopropylmethyl)-5-({[5-({[3-(dimethylamino)propyl]-amino}carbonyl)-1-methyl-1H pyrrol-3-yl]amino}carbonyl)-1H pyrrol-3-yl]-4-(formylamino)-1-methyl-1H pyrrole-2-carboxamide; or (g) N2,N7-Bis[5-({[4-({[3-(dimethylamino)propyl]amino}carbonyl)-5-isopropyl-1,3-thiazol-2-yl]amino}carbonyl)-1-methyl-1H pyrrol-3-yl]-9,10-dihydro-2,7-phenanthrenedicarboxamide.
28. A compound as claimed in Claim 27 which is N-[3-(dimethylamino)-propyl]-2-({[4-({[4-(formylamino)-1-methyl-1H pyrrol-2-yl]carbonyl}-amino)-1-methyl-1H- pyrrol-2-yl]carbonyl}amino)-5-isopropyl-1,3-thiazole-4-carboxamide.
29. A compound as claimed in any one of Claims 1 to 15, which binds to and/or has specificity for DNA sequences that contain at least one GC base pairing.
30. A compound as claimed in Claim 29, which is:
(i) a compound of formula I, as defined in any one of Claims 16 to 20 or 22 to 25, provided that the compound comprises at least one structural fragment of formula Id, Ie or If; or (ii) a compound of formula II, as defined in any one of Claims 21 to 25.
(i) a compound of formula I, as defined in any one of Claims 16 to 20 or 22 to 25, provided that the compound comprises at least one structural fragment of formula Id, Ie or If; or (ii) a compound of formula II, as defined in any one of Claims 21 to 25.
31. A compound as claimed in any one of Claims 1 to 25 which has different binding affinities at different minor groove binding sites in double-stranded DNA molecules having more than one minor groove binding site.
32. A compound as claimed in Claim 31, wherein the different minor groove binding sites comprise solely AT base pairs.
33. A pharmaceutical formulation including a compound as defined in any one of Claims 1 to 32 in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.
34. A pharmaceutical formulation for use in the treatment of a disease that relies upon DNA replication for its propagation, comprising a compound as defined in any one of Claims 1 to 32 in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.
35. A compound as defined in any one of Claims 1 to 32 for use as a pharmaceutical.
36. A compound as defined in any one of Claims 1 to 32 for use in the treatment of a disease that relies upon DNA replication for its propagation.
37. The use of a compound as defined in any of one Claims 1 to 32, as active ingredient for the manufacture of a medicament for use in the treatment of a disease that relies upon DNA replication for its propagation.
38. A method of treatment of a disease that relies upon DNA replication for its propagation, which method comprises administration of a therapeutically effective amount of a compound as defined in any of one Claims 1 to 32 to a person suffering from that disease.
39. A method of treating a viral, bacterial, fungal or other microbial (e.g.
parasitic) infection, where the viral, bacterial, fungal or other microbial (e.g.
parasitic) infective agent is resistant to one or more anti-viral, anti-bacterial, anti-fungal or other anti-microbial (e.g. anti-parasitic) agents, respectively, that do not act by inhibiting DNA replication, which method comprises administration of a therapeutically effective amount of a compound as defined in any one of Claims 1 to 32 to a person having that infection.
parasitic) infection, where the viral, bacterial, fungal or other microbial (e.g.
parasitic) infective agent is resistant to one or more anti-viral, anti-bacterial, anti-fungal or other anti-microbial (e.g. anti-parasitic) agents, respectively, that do not act by inhibiting DNA replication, which method comprises administration of a therapeutically effective amount of a compound as defined in any one of Claims 1 to 32 to a person having that infection.
40. A method of treatment of a disease that relies upon DNA replication for its propagation, which method comprises administration, to a person suffering from that disease, of a therapeutically effective amount of a compound as defined in any one of Claims 1 to 32 in combination with one or more other agents that are known to be effective in treating that disease.
41. A combination product comprising components:
(A) a formulation comprising a compound as defined in any one of Claims 1 to 32; and (B) a formulation comprising one or more other chemical agents that are known to be effective in treating diseases that rely upon DNA
replication for their propagation.
(A) a formulation comprising a compound as defined in any one of Claims 1 to 32; and (B) a formulation comprising one or more other chemical agents that are known to be effective in treating diseases that rely upon DNA
replication for their propagation.
42. A combination product as claimed in Claim 41, wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.
43. A combination product as claimed in Claim 41 or Claim 42, wherein (A) and (B) are presented as separate components.
43. A combination product as claimed in Claim 41 or Claim 42, wherein (A) and (B) are presented as a single formulation.
45. A method of inhibiting DNA replication, which method comprises contacting the DNA with an inhibitory amount of a compound as defined in any of one Claims 1 to 32.
46. A method of stabilising a DNA duplex formed between first and second single strands of DNA, which method comprises contacting that DNA duplex with a compound as defined in any of one Claims 1 to 32.
47. A method of enhancing the difference in melting temperatures between first and second DNA duplexes, wherein each DNA duplex is formed from a first single strand of DNA that is the same in each duplex and a second single strand of DNA that is different in each duplex, which method comprises contacting each DNA duplex with a compound as defined in any of one Claims 1 to 32.
48. A process for the preparation of compounds of formula I as defined in Claim 16 which comprises:
(a) reaction of a compound of formula III, wherein Aa represents A or, when a represents 0, then Aa may also represent A2 and Q, D, A and A2 are as defined in Claim 16 and a is as defined below, with a compound of formula IV, wherein Ab represents a direct bond or -A1-C(O)-, as appropriate, L1 represents a leaving group, a and b both represent integers from 0 to 5, the sum of the two being 2, 3, 4 or 5, and R1 and Q are as defined in Claim 16;
(b) for compounds of formula I in which R1 represents D-A-N(H)-[Q]n-C(O)-E-C(O)-, reaction of two equivalents of a compound of formula V, wherein Q, n, A and D are as defined in Claim 16, with a compound of formula VI, L2-C(O)-E-C(O)-L2 VI
wherein L2 represents a leaving group, the two L2 groups being the same or different, and E is as defined in Claim 16; or (c) deprotection of a protected derivative of a compound of formula I as 49. A compound of formula V, as defined in Claim 48, or a protected derivative thereof.
43. A combination product as claimed in Claim 41 or Claim 42, wherein (A) and (B) are presented as a single formulation.
45. A method of inhibiting DNA replication, which method comprises contacting the DNA with an inhibitory amount of a compound as defined in any of one Claims 1 to 32.
46. A method of stabilising a DNA duplex formed between first and second single strands of DNA, which method comprises contacting that DNA duplex with a compound as defined in any of one Claims 1 to 32.
47. A method of enhancing the difference in melting temperatures between first and second DNA duplexes, wherein each DNA duplex is formed from a first single strand of DNA that is the same in each duplex and a second single strand of DNA that is different in each duplex, which method comprises contacting each DNA duplex with a compound as defined in any of one Claims 1 to 32.
48. A process for the preparation of compounds of formula I as defined in Claim 16 which comprises:
(a) reaction of a compound of formula III, wherein Aa represents A or, when a represents 0, then Aa may also represent A2 and Q, D, A and A2 are as defined in Claim 16 and a is as defined below, with a compound of formula IV, wherein Ab represents a direct bond or -A1-C(O)-, as appropriate, L1 represents a leaving group, a and b both represent integers from 0 to 5, the sum of the two being 2, 3, 4 or 5, and R1 and Q are as defined in Claim 16;
(b) for compounds of formula I in which R1 represents D-A-N(H)-[Q]n-C(O)-E-C(O)-, reaction of two equivalents of a compound of formula V, wherein Q, n, A and D are as defined in Claim 16, with a compound of formula VI, L2-C(O)-E-C(O)-L2 VI
wherein L2 represents a leaving group, the two L2 groups being the same or different, and E is as defined in Claim 16; or (c) deprotection of a protected derivative of a compound of formula I as 49. A compound of formula V, as defined in Claim 48, or a protected derivative thereof.
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| GB0130868.3 | 2001-12-24 | ||
| PCT/GB2002/005916 WO2003059881A2 (en) | 2001-12-24 | 2002-12-24 | Dna minor groove binding compounds |
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| WO2005083114A1 (en) * | 2004-02-26 | 2005-09-09 | Thomsen Bioscience A/S | Method, kit and system for enhanced nested pcr |
| GB0412468D0 (en) * | 2004-06-04 | 2004-07-07 | Astrazeneca Ab | Chemical compounds |
| AU2006278998A1 (en) * | 2005-07-29 | 2007-02-15 | 4Sc Ag | Novel heterocyclic NF-kB inhibitors |
| GB0619325D0 (en) | 2006-09-30 | 2006-11-08 | Univ Strathclyde | New compounds |
| WO2013033658A1 (en) | 2011-09-02 | 2013-03-07 | Northwestern University | Self-assembled nanostructures |
| CN104845967B (en) | 2015-04-15 | 2020-12-11 | 苏州新海生物科技股份有限公司 | Oligonucleotide fragment, method for selectively amplifying target nucleic acid sequence variant by using same and application of oligonucleotide fragment |
| WO2018047148A1 (en) | 2016-09-12 | 2018-03-15 | Novartis Ag | Compounds for the inhibition of mirna |
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| CA1308516C (en) * | 1987-07-06 | 1992-10-06 | J. William Lown | Oligopeptide anticancer and antiviral agents |
| IL90337A0 (en) * | 1988-05-24 | 1989-12-15 | Pfizer | Aromatic and heterocyclic carboxamide derivatives as antineoplastic agents |
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| US5698674A (en) * | 1994-04-13 | 1997-12-16 | The Regents Of The University Of California | Triheterocyclic peptides capable of binding the minor and major grooves of DNA |
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| GB9623522D0 (en) | 1996-11-11 | 1997-01-08 | Pharmacia & Upjohn Spa | Benzoheterocycle distamycin derivatives process for preparing them and their use as antitumour and antiviral agents |
| WO2001019792A1 (en) | 1999-09-17 | 2001-03-22 | Genelabs Technologies, Inc. | Covalently linked dimeric dna binding molecules |
| ATE362940T1 (en) | 2000-03-16 | 2007-06-15 | Genesoft Inc | CHARGED COMPOUNDS WITH A NUCLEIC ACID BINDING UNIT AND THEIR USES |
| AU2001270183A1 (en) | 2000-06-27 | 2002-01-08 | Genelabs Technologies, Inc. | Novel compounds possessing antibacterial, antifungal or antitumor activity |
| WO2002101007A2 (en) | 2001-06-13 | 2002-12-19 | Genesoft Pharmaceuticals, Inc | Antipathogenic benzamide compounds |
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-
2001
- 2001-12-24 GB GBGB0130868.3A patent/GB0130868D0/en not_active Ceased
-
2002
- 2002-12-24 CA CA2470515A patent/CA2470515C/en not_active Expired - Lifetime
- 2002-12-24 WO PCT/GB2002/005916 patent/WO2003059881A2/en active Application Filing
- 2002-12-24 AU AU2002356319A patent/AU2002356319A1/en not_active Abandoned
- 2002-12-24 JP JP2003559985A patent/JP4624675B2/en not_active Expired - Lifetime
- 2002-12-24 EP EP02806338A patent/EP1467969B1/en not_active Expired - Lifetime
- 2002-12-24 KR KR1020047009988A patent/KR100966520B1/en active IP Right Grant
- 2002-12-24 AT AT02806338T patent/ATE509911T1/en not_active IP Right Cessation
- 2002-12-24 US US10/500,093 patent/US7700765B2/en active Active
- 2002-12-24 ES ES02806338T patent/ES2395273T3/en not_active Expired - Lifetime
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2010
- 2010-03-04 JP JP2010048022A patent/JP2010174023A/en active Pending
Also Published As
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|---|---|
| JP2005519064A (en) | 2005-06-30 |
| US7700765B2 (en) | 2010-04-20 |
| ATE509911T1 (en) | 2011-06-15 |
| WO2003059881A2 (en) | 2003-07-24 |
| EP1467969A2 (en) | 2004-10-20 |
| KR20040078651A (en) | 2004-09-10 |
| JP4624675B2 (en) | 2011-02-02 |
| EP1467969B1 (en) | 2011-05-18 |
| CA2470515C (en) | 2011-06-07 |
| WO2003059881A3 (en) | 2003-11-27 |
| US20070117760A1 (en) | 2007-05-24 |
| ES2395273T3 (en) | 2013-02-11 |
| KR100966520B1 (en) | 2010-06-29 |
| JP2010174023A (en) | 2010-08-12 |
| GB0130868D0 (en) | 2002-02-06 |
| AU2002356319A1 (en) | 2003-07-30 |
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