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US 7,582,655 B2Granted
Antineoplastic compounds
AssigneeUniversity of Saskatchewan
InventorsJonathan R. Dimmock, Umashankar Das
Life of this patent
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Abstract
The present invention relates to 4-piperidone derivatives represented by the following formula (I) and the acid addition salts thereof. The method of preparation and antineoplastic activity of the said compounds are disclosed. A number of the compounds possess submicromolar IC50 and CC50 values and have a selective toxicity for colon cancers and leukemic cells. In addition, many of the compounds are able to reverse multidrug resistance.
Claims16
A 4-piperidone compound represented by structural formula (I):
- wherein
- R1 and R2 independently represent a substituted or unsubstituted phenyl, said substituted phenyl having a single substituent at the 2, 3, or 4 position or having multiple independent substituents at the 2,3;
- 2,4;
- 2,5;
- 2,6;
- 3,4;
- 3,5;
- 3,6;
- 4,6;
- 2,3,4;
- 2,4.6;
- or 3,4,5 positions, said substituents being selected from the group consisting of halogen, alkoxy, alkyl, phenyl, nitro, and phosphonate groups;
- R3 and R4 independently represent H, alkyl, hydroxyalkyl, or carboxylate ester, wherein each R3 and each R4 may be the same or different;
- n represents an integer from 1 to 4 and indicates the number of Y(CH2)oZ substituents on the benzene ring;
- o represent an integer from 1 to 4;
- X represents (CH2)r, CO, COO, where r represents an integer from 1 to 4;
- Y represents O, S, NH, N(alkyl), N(aryl), or (CH2)s, where s represents an integer from 1 to 4;
- and
- Z represents N(alkyl)2, NH(alkyl), N(aryl)2, NH(aryl), +N(alkyl)3, or
- where B represents O, S, CH2, NH, N-alkyl, or N-aryl, p represents 1 or 2, and q represents 2 or 3;
- or a pharmaceutically acceptable salt thereof.
18 more elements
A 4-piperidone compound selected from the group consisting of:
- 1-[4-(2-Dimethylaminoethoxy)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidone hydrochloride (3a);
- 3,5-bis(4-Chlorophenylmethylene)-1-[4-(2-dimethylaminoethoxy)phenyl-carbonyl]-4-piperidone hydrochloride hemihydrate (3b);
- 1-[4-(2-Dimethylaminoethoxy)phenylcarbonyl]-3,5-bis(4-nitrophenylmethylene)-4-piperidone hydrochloride hemihydrate (3c);
- 1-[4-(2-Dimethylaminoethoxy)phenylcarbonyl]-3,5-bis(4-methylphenyl-methylene)-4-piperidone hydrochloride hemihydrate (3d);
- 1-[4-(2-Diethylaminoethoxy)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidone hydrochloride hemihydrate (4a);
- 3,5-bis(4-Chlorophenylmethylene)-1-[4-(2-diethylaminoethoxy)phenylcarbonyl]-4-piperidone hydrochloride (4b);
- 1-[4-(2-Diethylaminoethoxy)phenylcarbonyl]-3,5-bis(4-nitrophenylmethylene)-4-piperidone hydrochloride (4c);
- 1-[4-(2-Diethylaminoethoxy)phenylcarbonyl]-3,5-bis(4-methylphenylmethylene)-4-piperidone hydrochloride (4d);
- 1-[4-{2-(1-Piperidinyl)ethoxy}phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidone hydrochloride hemihydrate (5a);
- 3,5-bis(4-Chlorophenylmethylene)-1-[4-{2-(1-piperidinyl)ethoxy}phenylcarbonyl]-4-piperidone hydrochloride (5b);
- 3,5-bis(4-Nitrophenylmethylene)-1-[4-{2-(1-piperidinyl)ethoxy}phenylcarbonyl]-4-piperidone hydrochloride 1.5 hydrate (5c);
- 3,5-bis(4-Methylphenylmethylene)-1-[4-{1-piperidinyl)ethoxy}phenylcarbonyl]-4-piperidone hydrochloride hemihydrate (5d);
- 1-[4-{2-(4-Morpholinyl)ethoxy}phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidone hydrochloride hemihydrate (6a);
- 3,5-bis(4-Chlorophenylmethylene)-1-[4-{2-(4-morpholinyl)ethoxy}phenylcarbonyl-4-piperidone hydrochloride (6b);
- 1-[4-{2-(4-Morpholinyl)ethoxy}phenylcarbonyl]-3,5-bis(4-nitrophenylmethylene)-4-piperidone hydrochloride hemihydrate (6c);
- and
- 3,5-bis(4-Methylphenylmethylene)-1-[4-{2-(4-morpholinyl)ethoxy}phenylcarbonyl]-4-piperidone hydrochloride hemihydrate (6d).
14 more elements
Dependencies are inferred from the claim text.