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WO1990009092A3 - Novel potent inducers of terminal differentiation and method of use thereof - Google Patents

Novel potent inducers of terminal differentiation and method of use thereof Download PDF

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Publication number
WO1990009092A3
WO1990009092A3 PCT/US1989/005203 US8905203W WO9009092A3 WO 1990009092 A3 WO1990009092 A3 WO 1990009092A3 US 8905203 W US8905203 W US 8905203W WO 9009092 A3 WO9009092 A3 WO 9009092A3
Authority
WO
WIPO (PCT)
Prior art keywords
compound
amount
patient
terminal differentiation
proliferation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1989/005203
Other languages
French (fr)
Other versions
WO1990009092A2 (en
Inventor
Paul A Marks
Richard A Rifkind
Ronald Breslow
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Columbia University in the City of New York
Memorial Sloan Kettering Cancer Center
Original Assignee
Columbia University in the City of New York
Memorial Sloan Kettering Cancer Center
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US07/374,343 external-priority patent/US5055608A/en
Application filed by Columbia University in the City of New York, Memorial Sloan Kettering Cancer Center filed Critical Columbia University in the City of New York
Priority to PCT/US1990/002690 priority Critical patent/WO1991000257A1/en
Priority to AU59271/90A priority patent/AU5927190A/en
Priority to US07/522,558 priority patent/US5175191A/en
Publication of WO1990009092A2 publication Critical patent/WO1990009092A2/en
Publication of WO1990009092A3 publication Critical patent/WO1990009092A3/en
Priority to AT91901442T priority patent/ATE175185T1/en
Priority to CA002068224A priority patent/CA2068224C/en
Priority to EP91901442A priority patent/EP0594577B1/en
Priority to PCT/US1990/006649 priority patent/WO1991008191A1/en
Priority to AU69726/91A priority patent/AU643248B2/en
Priority to ES91901442T priority patent/ES2128314T3/en
Priority to JP03501924A priority patent/JP3083842B2/en
Priority to DE69032871T priority patent/DE69032871T2/en
Anticipated expiration legal-status Critical
Priority to US08/424,556 priority patent/US5608108A/en
Priority to US08/476,624 priority patent/US5840960A/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
    • C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/36—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
    • C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
    • C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C243/28—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • C07D231/28—Two oxygen or sulfur atoms
    • C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
    • C07D231/32—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • C07D239/62—Barbituric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a class of compounds having two or more nonpolar components connected by a polar group and having polar groups on the termini of the compound. The invention also concerns a method of selectively inducing termini differentiation of neoplastic cells and thereby inhibiting proliferation of such cells which comprises contacting the cells under suitable condition with an amount of the compound effect to selectively induce terminal differentiation. Moreover, the invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells which comprises administering to the patient an amount of the compound effective to selectively induce terminal differentiation of such neoplastic cells, thereby inhibiting their proliferation and suppressing oncogenicity. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound in an amount effective less than an amount which would cause toxicity in the patient.
PCT/US1989/005203 1988-11-14 1989-11-14 Novel potent inducers of terminal differentiation and method of use thereof Ceased WO1990009092A2 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
PCT/US1990/002690 WO1991000257A1 (en) 1989-06-30 1990-05-14 Novel potent inducers of terminal differentiation and methods of use thereof
AU59271/90A AU5927190A (en) 1989-06-30 1990-05-14 Novel potent inducers of terminal differentiation and methods of use thereof
US07/522,558 US5175191A (en) 1988-11-14 1990-05-14 Potent inducers of terminal differentiation and methods of use thereof
DE69032871T DE69032871T2 (en) 1989-11-14 1990-11-14 NEW POTENTIAL INDUCTORS OF TERMINAL DIFFERENTIATION AND METHOD FOR THEIR USE
JP03501924A JP3083842B2 (en) 1989-11-14 1990-11-14 Novel and potent terminal differentiation inducer and method of using the same
ES91901442T ES2128314T3 (en) 1989-11-14 1990-11-14 NEW POWERFUL TERMINAL DIFFERENTIATION INDUCTORS AND METHOD OF USE THEREOF.
CA002068224A CA2068224C (en) 1989-11-14 1990-11-14 Novel potent inducers of terminal differentiation and method of use thereof
AT91901442T ATE175185T1 (en) 1989-11-14 1990-11-14 NEW POTENT INDUCTORS OF TERMINAL DIFFERENTIATION AND METHOD OF USE THEREOF
EP91901442A EP0594577B1 (en) 1989-11-14 1990-11-14 Novel potent inducers of terminal differentiation and method of use thereof
PCT/US1990/006649 WO1991008191A1 (en) 1989-11-14 1990-11-14 Novel potent inducers of terminal differentiation and method of use thereof
AU69726/91A AU643248B2 (en) 1989-11-14 1990-11-14 Novel potent inducers of terminal differentiation and method of use thereof
US08/424,556 US5608108A (en) 1988-11-14 1995-04-17 Potent inducers of terminal differentiation and method of use thereof
US08/476,624 US5840960A (en) 1988-11-14 1995-06-07 Potent inducers of terminal differentiation and method of use thereof

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US27096388A 1988-11-14 1988-11-14
US270,963 1988-11-14
US374,343 1989-06-30
US07/374,343 US5055608A (en) 1988-11-14 1989-06-30 Novel potent inducers of thermal differentiation and method of use thereof

Publications (2)

Publication Number Publication Date
WO1990009092A2 WO1990009092A2 (en) 1990-08-23
WO1990009092A3 true WO1990009092A3 (en) 1990-10-04

Family

ID=26954600

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1989/005203 Ceased WO1990009092A2 (en) 1988-11-14 1989-11-14 Novel potent inducers of terminal differentiation and method of use thereof

Country Status (4)

Country Link
JP (1) JPH04500359A (en)
AU (1) AU4835090A (en)
CA (1) CA2002853A1 (en)
WO (1) WO1990009092A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69032871T2 (en) * 1989-11-14 1999-09-09 Sloan-Kettering Institute For Cancer Research NEW POTENTIAL INDUCTORS OF TERMINAL DIFFERENTIATION AND METHOD FOR THEIR USE
WO2003032921A2 (en) * 2001-10-16 2003-04-24 Sloan-Kettering Institute For Cancer Research Treatment of neurodegenerative diseases and cancer of the brain

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4614815A (en) * 1979-09-10 1986-09-30 Anic S.P.A. Process for producing diesterdiamides
US4882346A (en) * 1987-06-16 1989-11-21 The United States Of America As Reprsented By The Department Of Health And Human Services Chemical differentiating agents

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4614815A (en) * 1979-09-10 1986-09-30 Anic S.P.A. Process for producing diesterdiamides
US4882346A (en) * 1987-06-16 1989-11-21 The United States Of America As Reprsented By The Department Of Health And Human Services Chemical differentiating agents

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PROC. NATL. ACAD. SCI. U.S.A., Vol. 72, March 1975, TANAKA et al., "Induction of Erythroid Differentiation in Murine Virus Infected Erythroleukemia Cells by Highly Polar Compounds", pages 1003-1006. *
THE JOURNAL OF BIOLOGICAL CHEMISTRY, Vol. 253, No. 12, June 1978, REUBEN et al., "Inducers of Erythroleukemic Differentiation", pages 4214-4218. *

Also Published As

Publication number Publication date
JPH04500359A (en) 1992-01-23
WO1990009092A2 (en) 1990-08-23
AU4835090A (en) 1990-09-05
CA2002853A1 (en) 1990-05-14

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