Heterocyclic hydrazones for use as anti-cancer agents
AssigneeAustria Wirtschaftsservice Gesellschaft Mit Beschrankter Haftung
InventorsJohann Hofmann, Gottfried Heinisch, Johnny Easmon, Gerhard Purstinger, Heinz-Herbert Fiebig
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Abstract
The invention relates to novel 2-benzimidazolyl-, 2-benzoxazolyl- and 2-benzothiazolyl hydrazones that are derived from 2-formylpyridine, 2-acylpyridines, acetyldiazines and acetyl(iso)quinolines. The invention also relates to a novel method for producing 2-benzimidazolyl-, 2-benzoxazolyl- and 2-benzothiazolyl hydrazones and to their use as useful anti-cancer therapeutic agents. The novel compounds are also active against multidrug-resistant cancer cells.
Claims12
A compound of the general formula:
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- wherein
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- and wherein R═H, CH3, OCH3, OH, Cl, Br, F, CF3, NO2, NH2, NHCOCH3, N(CH3)2, phenyl, CN, C═NH(NH2), C═S(NH2), C═NH(NHOH), COOH or COOR4, wherein R4=an aliphatic residue or a phenyl group, or CONR5R6, wherein R5 and R6 are H, an aliphatic substituent or a phenyl group,
- R1═H, methyl, ethyl, propyl, iso-propyl, butyl, tert.-butyl, cycloprpyl, cyclohexyl, phenyl, benzyl or 2-pyridyl, and X═O, S, NH or N—R2, wherein R2 methyl, ethyl, propyl, sec.-propyl, butyl, tert.-butyl, allyl, cyclopropyl, phenyl, benzyl, CH2—CH2—O—CH3 or CH2—CH2-n(CH3)2,
- with the proviso that if
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- wherein R═H,
- in case X═S:
- R1 is not H, methyl, phenyl or 2-pyridyl,
- in case X═O:
- R1 is not methyl,
- in case X═N:
- R1 is not H,
- in case X═NH:
- R1 is not methyl,
- in case X═N—R2 with R2═CH3:
- R1 is not methyl;
- with the further proviso that if
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- in case X═S:
- R1 is not methyl;
- with the further proviso that if
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- in case X═S:
- R1 is not H or methyl;
- with the further proviso that if
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- in case X═S and R1=methyl:
- R is not H or methyl;
- with the further proviso that if
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- in case X═S and R1=methyl:
- R is not methyl;
- with the further proviso that if
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- in case X═S and R1=methyl:
- R is not H;
- as well as with the proviso that if
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- in case X═S and R1═H:
- R in position 6 is not methyl;
- as well as the pharmaceutically acceptable salts thereof.
A method of preparing a compound of the general formula
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- wherein Het=
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- and wherein R═H, CH3, OCH3, OH, Cl, Br, F, CF3, NO2, NH2, NHCOCH3, N(CH3)2, phenyl, CN, C═NH(NH2), C═S(NH2), C═NH(NHOH), COOH or COOR4, wherein R4 is an aliphatic residue or a phenyl group, or CONR5R6, wherein R5 and R6 are H, an aliphatic substituent or a phenyl group,
- R1═H, methyl, ethyl, propyl, iso-propyl, butyl, tert.-butyl, cyclopropyl, cyclohexyl, phenyl, benzyl, or 2-pyridyl, and X═O, S, NH or N—R2, wherein R2=methyl, ethyl, propyl, sec-propyl, butyl, tert.-butyl, allyl, cyclopropyl, phenyl, benzyl, CH2—CH2—O—CH3 or CH2—CH2—N(CH3)2, with the proviso that if X═S and Het=pyridinyl, then R1 is not H or methyl, characterised in that a ketone of the general formula (III)
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- wherein Het and R1 are as defined above, is reacted with a hydrazine of the general formula (II)
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- wherein X is as defined above.
The use of a compound of the general formula:
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- wherein
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- and wherein R═H, CH3, OCH3, OH, Cl, Br, F, CF3, NO2, NH2, NHCOCH3, N(CH3)2, phenyl, CN, C═NH(NH2), C═S(NH2), C═NH(NHOH), COOH or COOR4, wherein R4=an aliphatic residue or a phenyl group, or CONR5R6, wherein R5 and R6 are H, an aliphatic substituent or a phenyl group,
- R1 is Hi methyl, ethyl, propyl, iso-propyl, butyl, tert.-butyl, cyclopropyl, cyclohexyl, phenyl, benzyl, or 2-pyridyl, and X═O, S, NH or N—R2, wherein R2=methyl, ethyl, propyl, sec-propyl, butyl, tert.-butyl, allyl, cyclopropyl, phenyl, benzyl, CH2—CH2—O—CH3 or CH2—CH2—N(CH3)2, with the proviso that if X═S and Het=pyridinyl, then R1 is not H or methyl;
- as well as the pharmaceutically acceptable salts as medicament.
Dependencies are inferred from the claim text.