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
Authority
WO
WIPO (PCT)
Prior art keywords
paclitaxel
compounds
tubulin polymerization
designing
stabilize
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
Application filed by Cytoclonal Pharmaceutics Inc, Dorit Arad, Arthur P Bollon, Bradley W Poland, David C Young filed Critical Cytoclonal Pharmaceutics Inc
Priority to EP00947487A priority Critical patent/EP1198461A2/en
Priority to CA002379676A priority patent/CA2379676A1/en
Priority to AU61083/00A priority patent/AU6108300A/en
Publication of WO2001005779A2 publication Critical patent/WO2001005779A2/en
Publication of WO2001005779A3 publication Critical patent/WO2001005779A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters 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
    • C07C271/22—Esters 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C233/58—Carboxylic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/81—Carboxylic 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
    • C07C233/82—Carboxylic 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
    • C07C233/87—Carboxylic 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
    • 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
    • C07C235/02—Carboxylic 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
    • C07C235/04—Carboxylic 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
    • C07C235/14—Carboxylic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/44—Systems 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 WO2001005779A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP00947487A EP1198461A2 (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers
CA002379676A CA2379676A1 (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers
AU61083/00A AU6108300A (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US14397399P 1999-07-15 1999-07-15
US60/143,973 1999-07-15
US17189299P 1999-12-23 1999-12-23
US60/171,892 1999-12-23

Publications (2)

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

Family

ID=26841562

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/019524 WO2001005779A2 (en) 1999-07-15 2000-07-17 Method of designing tubulin polymerization stabilizers

Country Status (4)

Country Link
EP (1) EP1198461A2 (en)
AU (1) AU6108300A (en)
CA (1) CA2379676A1 (en)
WO (1) WO2001005779A2 (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
EP1198461A2 (en) 2002-04-24
AU6108300A (en) 2001-02-05
WO2001005779A2 (en) 2001-01-25
CA2379676A1 (en) 2001-01-25

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