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1. (WO1991008191) NOVEL POTENT INDUCERS OF TERMINAL DIFFERENTIATION AND METHOD OF USE THEREOF
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/1991/008191 International Application No.: PCT/US1990/006649
Publication Date: 13.06.1991 International Filing Date: 14.11.1990
Chapter 2 Demand Filed: 10.06.1991
IPC:
C07C 233/05 (2006.01) ,C07C 233/07 (2006.01) ,C07C 233/36 (2006.01) ,C07C 243/28 (2006.01) ,C07C 259/06 (2006.01) ,C07C 259/08 (2006.01) ,C07D 231/32 (2006.01) ,C07D 239/62 (2006.01) ,C07D 243/08 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
233
Carboxylic acid amides
01
having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
02
having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
04
with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic saturated carbon skeleton
05
having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
233
Carboxylic acid amides
01
having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
02
having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
04
with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic saturated carbon skeleton
07
having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
233
Carboxylic acid amides
01
having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
34
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
35
with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
36
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
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
243
Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
24
Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
26
with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
28
to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
259
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
04
without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
06
having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
259
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
04
without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
08
having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
231
Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
02
not condensed with other rings
10
having two or three double bonds between ring members or between ring members and non-ring members
14
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
28
Two oxygen or sulfur atoms
30
attached in position 3 and 5
32
Oxygen atoms
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
239
Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
02
not condensed with other rings
24
having three or more double bonds between ring members or between ring members and non-ring members
28
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
46
Two or more oxygen, sulfur or nitrogen atoms
60
Three or more oxygen or sulfur atoms
62
Barbituric acids
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
243
Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
06
having the nitrogen atoms in positions 1 and 4
08
not condensed with other rings
Applicants:
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH [US/US]; 1275 York Avenue New York, NY 10021, US (AllExceptUS)
THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK [US/US]; West 116th Street & Broadway New York, NY 10027, US (AllExceptUS)
MARKS, Paul, A. [US/US]; US (UsOnly)
RIFKIND, Richard, A. [US/US]; US (UsOnly)
BRESLOW, Ronald [US/US]; US (UsOnly)
JURSIC, Branko [US/US]; US (UsOnly)
Inventors:
MARKS, Paul, A.; US
RIFKIND, Richard, A.; US
BRESLOW, Ronald; US
JURSIC, Branko; US
Agent:
WHITE, John, P.; Cooper & Dunham 30 Rockefeller Plaza New York, NY 10112, US
Priority Data:
522,55814.05.1990US
PCT/US89/0520314.11.1989US
PCT/US90/0269014.05.1990US
Title (EN) NOVEL POTENT INDUCERS OF TERMINAL DIFFERENTIATION AND METHOD OF USE THEREOF
(FR) NOUVEAUX INDUCTEURS PUISSANTS DE DIFFERENCIATION DE TERMINAISONS ET LEUR MODE D'EMPLOI
Abstract:
(EN) The invention provides compounds, several of which belong to a class having two or more nonpolar components connected by a polar group and having polar groups on the termini of the compound. The invention also concents 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 effective 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.
(FR) Sont décrits des composés dont certains appartiennent à une classe présentant deux composants non polaires ou plus, connectés par un groupe polaire et dotés de groupes polaires aux terminaisons du composé. L'invention concerne également un procédé d'induction sélective d'une différenciation de terminaisons de cellules néoplastiques, et par conséquent d'inhibition de la prolifération desdites cellules, consistant à mettre en contact les cellules dans des conditions adaptées, avec une quantité du composé suffisante pour induire sélectivement une différenciation de terminaisons. De plus, l'invention concerne un procédé de traitement d'un patient présentant une tumeur caractérisée par la prolifération de cellules néoplastiques, consistant à administrer au patient une dose du composant suffisante pour induire sélectivement la différenciation des terminaisons desdites cellules néoplastiques, inhibant ainsi leur prolifération et supprimant l'oncogénicité. En outre, l'invention concerne une préparation pharmaceutique comprenant un excipient acceptable en pharmacologie, ainsi que le composé en une dose efficace, inférieure à une dose susceptible de provoquer une toxicité chez le patient.
Designated States: AU, CA, DK, FI, HU, JP, KR, NO, US
European Patent Office (AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LU, NL, SE)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
EP0594577US5608108JP3083842JPH05504339CA2068224AU1991069726