WO2001005779A3 - Method of designing tubulin polymerization stabilizers - Google Patents

Method of designing tubulin polymerization stabilizers Download PDF

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Publication number
WO2001005779A3
WO2001005779A3 PCT/US2000/019524 US0019524W WO0105779A3 WO 2001005779 A3 WO2001005779 A3 WO 2001005779A3 US 0019524 W US0019524 W US 0019524W WO 0105779 A3 WO0105779 A3 WO 0105779A3
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WO
Grant status
Application
Patent type
Prior art keywords
paclitaxel
compounds
tubulin polymerization
designing
method
Prior art date
Application number
PCT/US2000/019524
Other languages
French (fr)
Other versions
WO2001005779A2 (en )
Inventor
Dorit Arad
Arthur P Bollon
Bradley W Poland
David C Young
Original Assignee
Cytoclonal Pharmaceutics Inc
Dorit Arad
Arthur P Bollon
Bradley W Poland
David C Young
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

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06Esters of carbamic acids
    • C07C271/08Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/57Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C233/58Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/64Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/81Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/82Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/87Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/14Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00Systems containing two condensed rings
    • C07C2602/36Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/44Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing eight carbon atoms

Abstract

A method for designing paclitaxel alternative compounds which stabilize the tubulin polymerization process has been found. These compounds in solution possess steric conformational properties of natural paclitaxel and are capable of binding to the tubulin protein at the same site where paclitaxel is known to bind. The compounds of the present invention stabilize tubulin polymerization in a way that is mechanistically equivalent to activity mechanism of paclitaxel. The compounds of the present invention have increased solubility, simpler synthesis, and the possibility for specificity and optimization due to the combinatorial reactions over natural paclitaxel.
PCT/US2000/019524 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers WO2001005779A3 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US14397399 true 1999-07-15 1999-07-15
US60/143,973 1999-07-15
US17189299 true 1999-12-23 1999-12-23
US60/171,892 1999-12-23

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP20000947487 EP1198461A2 (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers
CA 2379676 CA2379676A1 (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers

Publications (2)

Publication Number Publication Date
WO2001005779A2 true WO2001005779A2 (en) 2001-01-25
WO2001005779A3 true true WO2001005779A3 (en) 2001-08-16

Family

ID=26841562

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/019524 WO2001005779A3 (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers

Country Status (3)

Country Link
EP (1) EP1198461A2 (en)
CA (1) CA2379676A1 (en)
WO (1) WO2001005779A3 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4349552A (en) * 1978-10-30 1982-09-14 Fujisawa Pharmaceutical Company, Ltd. 5-Fluorouracil derivatives, and their pharmaceutical compositions
US5302589A (en) * 1992-08-07 1994-04-12 Glaxo, Inc. Heterocyclic inhibitors of 5-α-testosterone reductase
US5658940A (en) * 1995-10-06 1997-08-19 Celgene Corporation Succinimide and maleimide cytokine inhibitors
US5674905A (en) * 1992-06-19 1997-10-07 James Black Foundation Limited Bicyclooctane and bicycloheptane derivatives

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4349552A (en) * 1978-10-30 1982-09-14 Fujisawa Pharmaceutical Company, Ltd. 5-Fluorouracil derivatives, and their pharmaceutical compositions
US5674905A (en) * 1992-06-19 1997-10-07 James Black Foundation Limited Bicyclooctane and bicycloheptane derivatives
US5302589A (en) * 1992-08-07 1994-04-12 Glaxo, Inc. Heterocyclic inhibitors of 5-α-testosterone reductase
US5658940A (en) * 1995-10-06 1997-08-19 Celgene Corporation Succinimide and maleimide cytokine inhibitors

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
M. WANG ET. AL.: "A Unified and Quantitative Receptor Model for the Microtubule Binding of Paclitaxel and Epothilone.", ORGANIC LETTERS, vol. 1, no. 1, January 1999 (1999-01-01), pages 43 - 6, XP000983329 *
TING-CHAO CHOU ET. AL.: "Computerised Quantitation of Synergism and Antagonism of Taxol, Topotecan and Cisplatin Against Human Teratocarcinoma Cell Growth.", JOURNAL OF THE NATIONAL CANCER INSTITUTE, vol. 86, no. 20, 19 October 1994 (1994-10-19), pages 1517 - 24, XP000983664 *

Also Published As

Publication number Publication date Type
CA2379676A1 (en) 2001-01-25 application
WO2001005779A2 (en) 2001-01-25 application
EP1198461A2 (en) 2002-04-24 application

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