You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 28, 2024

Details for Patent: 6,087,367


✉ Email this page to a colleague

« Back to Dashboard


Title: Potent inducers of terminal differentiation and methods of use thereof
Abstract:The present invention provides the compound having the structure: ##STR1## wherein each of R.sub.1 and R.sub.2 are independently the same as or different from each other; when R.sub.1 and R.sub.2 are the same, each is a substituted or unsubstituted arylamino, cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiozoleamino group; when R.sub.1 and R.sub.2 are different, R.sub.1 =R.sub.3 --N--R.sub.4, wherein each of R.sub.3 and R.sub.4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R.sub.3 and R.sub.4 bond together to form a piperidine group and R.sub.2 is a hydroxylamino, hydroxyl, amino, alkylamino, dialkylamino or alkyloxy group; and n is an integer from about 4 to about 8. The present invention also provides a method of selectively inducing terminal differentiation of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.
Inventor(s): Breslow; Ronald (Englewood, NJ), Marks; Paul A. (Bridgewater, CT), Rifkind; Richard A. (New York, NY), Jursic; Branko (New Orleans, LA)
Assignee: Sloan-Kettering Institute for Cancer Research (New York, NY) The Trustees of Columbia University in the City of New York (New York, NY)
Filing Date:May 18, 1999
Application Number:09/314,195
Claims:1. A method of selectively inducing terminal differentiation of neoplastic cells and thereby inhibiting proliferation of such cells which comprises contacting the cells under suitable conditions with an effective amount of the compound having the structure: ##STR108## wherein each of R.sub.1 and R.sub.2 are independently the same as or different from each other; when R.sub.1 and R.sub.2 are the same, each is a substituted or unsubstituted cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiazoleamino group; when R.sub.1 and R.sub.2 are different, R.sub.1 =R.sub.3 -N-R.sub.4, wherein each of R.sub.3 and R.sub.4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R.sub.3 and R.sub.4 bond together to form a piperidine group and R.sub.2 is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from 4 to 8, or a pharmaceutically acceptable salt thereof; and wherein the amount of the compound is effective to selectively induce terminal differentiation.

2. A method of claim 1 wherein the R.sub.1 represents NHOH, R.sub.2 represents OH, and n represents 6.

3. A method of claim 1 wherein the compound has the structure: ##STR109## wherein each of R.sub.3 and R.sub.4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R.sub.3 and R.sub.4 bond together to form a piperidine group; R.sub.2 is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from 4 to 8, or a pharmaceutically acceptable salt thereof; and wherein the amount of compound is effective to selectively induce terminal differentiation.

4. A method of treating a patient having a tumor characterized by proliferation of neoplastic cells which comprises administering to the patient an effective amount of the compound having the structure: ##STR110## wherein each of R.sub.1 and R.sub.2 are independently the same as or different from each other; when R.sub.1 and R.sub.2 are the same, each is a substituted or unsubstituted cycloalkylamino, pyridineamino, piperidino, 9-purine-6-amine, or thiazoleamino group; when R.sub.1 and R.sub.2 are different, R.sub.1 =R.sub.3 --N--R.sub.4, wherein each of R.sub.3 and R.sub.4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R.sub.3 and R.sub.4 bond together to form a piperidine group and R.sub.2 is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from 4 to 8, or a pharmaceutically acceptable salt thereof; and wherein the amount of compound is effective to selectively induce terminal differentiation of such neoplastic cells and thereby inhibit their proliferation.

5. A method of claim 4 wherein the R.sub.1 represents NHOH, R.sub.2 represents OH, and n represents 6.

6. A method of claim 4 wherein the compound has the structure: ##STR111## wherein each of R.sub.3 and R.sub.4 are independently the same as or different from each other and are a hydrogen atom, a hydroxyl group, a substituted or unsubstituted, branched or unbranched alkyl, alkenyl, cycloalkyl, aryl, alkyloxy, aryloxy, arylalkyloxy, or pyridine group, or R.sub.3 and R.sub.4 bond together to form a piperidine group; R.sub.2 is a hydroxylamino, hydroxyl, amino, alkylamino, or alkyloxy group; and n is an integer from 4 to 8, or a pharmaceutically acceptable salt thereof; and wherein the amount of compound is effective to selectively induce terminal differentiation of such neoplastic cells and thereby inhibit their proliferation.

7. A method of claim 4 wherein the R.sub.2 of the structure is a hydroxylamino, hydroxyl, amino, methylamino, or methyoxy group and n is 6.

8. A method of claim 4 wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a substituted or unsubstituted phenyl group.

9. A method of claim 8 wherein the phenyl group is substituted with a methyl, cyano, nitro, trifluoromethyl, amino, aminocarbonyl, methylcyano, chloro, fluoro, bromo, iodo, 2,3-difluoro, 2,4-difluoro, 2,5-difluoro, 3,4-difluoro, 3,5-difluoro, 2,6-difluoro, 1,2,3-trifluoro, 2,3,6-trifluoro, 2,4,6-trifluoro, 3,4,5-trifluoro, 2,3,5,6-tetrafluoro, 2,3,4,5,6-pentafluoro, azido, hexyl, t-butyl, phenyl, carboxyl, hydroxyl, methoxy, phenyloxy, benzyloxy, phenylaminooxy, phenylaminocarbonyl, methyoxycarbonyl, methylaminocarbonyl, dimethylamino, dimethylaminocarbonyl, or hydroxylaminocarbonyl group.

10. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a cyclohexyl group.

11. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a methyoxy group.

12. A method of claim 6, wherein R.sub.3 and R.sub. bond together to form a piperidine group.

13. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a hydroxyl group.

14. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a benzyloxy group.

15. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a .delta.-pyridine group.

16. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a .beta.-pyridine group.

17. A method of claim 6, wherein R.sub.4 of the structure is a hydrogen atom and R.sub.3 is a .alpha.-pyridine group.

18. A method of claim 6, wherein R.sub.3 and R.sub.4 are both methyl groups.

19. A method of claim 6, wherein R.sub.4 of the structure is a methyl group and R.sub.3 is a phenyl group.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.