Title:
BICYCLIC DIHYDROPYRIMIDINES AS EG5 INHIBITORS
Document Type and Number:
WIPO Patent Application WO2006074293
Kind Code:
A3
Abstract:
The present invention provides compounds having formula (I): (I) and pharmaceutically acceptable derivatives thereof; as described generally and in subclasses herein, which compounds are useful as kinesin inhibitors (e.g., Eg5 inhibitors), and thus are useful, for example, for the treatment of proliferative disorders e.g., cancer. The invention additionally provides methods for preparing compounds of the invention, compositions comprising them, and methods for the use thereof in the treatment of various disorders where Eg5 is involved. In certain embodiments, the present invention provides for compounds, compositions, methods and systems for inhibiting cell growth. More specifically, the present invention provides for methods, compounds and compositions which are capable of inhibiting mitosis in metabolically active cells. Compounds, compositions and methods of the present invention inhibit the activity of a protein involved in the assembly and maintenance of the mitotic spindle. One class of proteins which acts on the mitotic spindle is the family of mitotic kinesins, a subset of the kinesin superfamily.
Inventors:
MAZITSCHEK RALPH (US)
TALLARICO JOHN A (US)
MALIGA ZOLTAN (US)
MITCHISON TIMOTHY J (US)
TALLARICO JOHN A (US)
MALIGA ZOLTAN (US)
MITCHISON TIMOTHY J (US)
Application Number:
PCT/US2006/000300
Publication Date:
November 09, 2006
Filing Date:
January 06, 2006
Export Citation:
Assignee:
HARVARD COLLEGE (US)
MAZITSCHEK RALPH (US)
TALLARICO JOHN A (US)
MALIGA ZOLTAN (US)
MITCHISON TIMOTHY J (US)
MAZITSCHEK RALPH (US)
TALLARICO JOHN A (US)
MALIGA ZOLTAN (US)
MITCHISON TIMOTHY J (US)
International Classes:
C07D471/04; A61K31/52; A61P35/00; C07D487/04; C07D491/04
Domestic Patent References:
| WO2004112719A2 | 2004-12-29 | |||
| WO2002078639A2 | 2002-10-10 |
Other References:
CHIBA, TAKUO ET AL: "Synthesis of furo[3,4-d]pyrimidine derivatives using ethyl 4-bromoacetoacetate", HETEROCYCLES , 22(3), 493-6 CODEN: HTCYAM; ISSN: 0385-5414, 1984, XP009068826
ZIGEUNER, GUSTAV ET AL: "Heterocycles. XII. Bromination of 2-oxo-6-methyl-tetrahydropyrimidines", MONATSHEFTE FUER CHEMIE , 97(5), 1408-21 CODEN: MOCHAP, 1966, XP009068816
ZIGEUNER G ET AL: "UEBER HETEROCYCLEN, 22. MITT.: 3,4,6,7-TETRAHYDRO-5-PYRROLOÄ3,4-DÜPYR IMIDIN-2(1H),5-DIONE HETEROCYCLES XXII: 3.4.6.7-TETRAHYDRO-5H-PYRROLOÄ3.4-DÜ-PYRIMIDINE-2( 1H)-5-DIONES", MONATSHEFTE FUR CHEMIE, SPRINGER VERLAG. WIEN, AT, vol. 101, no. 5, 1970, pages 1541 - 1546, XP001189611, ISSN: 0026-9247
GEORGE T ET AL: "CONDENSED HETEROCYCLES FROM 5-ETHOXYCARBONYL-6-METHYLTETRAHYDROPYRIMI DIN-2-ONES", SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE, no. 6, June 1975 (1975-06-01), pages 405 - 407, XP001189612, ISSN: 0039-7881
PEREZ R ET AL: "REACELESS SOLID-PHASE SYNTHESIS OF BICYCLIC DHYDROPYRIMIDONES USING MULTIDIRECTIONAL CYCLIZATION CLEAVAGE", JOURNAL OF COMBINATORIAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US, vol. 4, no. 5, 2002, pages 501 - 510, XP001193818, ISSN: 1520-4766
SINGH, KAMALJIT ET AL: "Metalation of Biginelli Compounds. A General Unprecedented Route to C-6 Functionalized 4-Aryl-3,4-dihydropyrimidinones", JOURNAL OF ORGANIC CHEMISTRY , 70(15), 6114-6117 CODEN: JOCEAH; ISSN: 0022-3263, 2005, XP002388295
ZIGEUNER, GUSTAV ET AL: "Heterocycles. XII. Bromination of 2-oxo-6-methyl-tetrahydropyrimidines", MONATSHEFTE FUER CHEMIE , 97(5), 1408-21 CODEN: MOCHAP, 1966, XP009068816
ZIGEUNER G ET AL: "UEBER HETEROCYCLEN, 22. MITT.: 3,4,6,7-TETRAHYDRO-5-PYRROLOÄ3,4-DÜPYR IMIDIN-2(1H),5-DIONE HETEROCYCLES XXII: 3.4.6.7-TETRAHYDRO-5H-PYRROLOÄ3.4-DÜ-PYRIMIDINE-2( 1H)-5-DIONES", MONATSHEFTE FUR CHEMIE, SPRINGER VERLAG. WIEN, AT, vol. 101, no. 5, 1970, pages 1541 - 1546, XP001189611, ISSN: 0026-9247
GEORGE T ET AL: "CONDENSED HETEROCYCLES FROM 5-ETHOXYCARBONYL-6-METHYLTETRAHYDROPYRIMI DIN-2-ONES", SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE, no. 6, June 1975 (1975-06-01), pages 405 - 407, XP001189612, ISSN: 0039-7881
PEREZ R ET AL: "REACELESS SOLID-PHASE SYNTHESIS OF BICYCLIC DHYDROPYRIMIDONES USING MULTIDIRECTIONAL CYCLIZATION CLEAVAGE", JOURNAL OF COMBINATORIAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US, vol. 4, no. 5, 2002, pages 501 - 510, XP001193818, ISSN: 1520-4766
SINGH, KAMALJIT ET AL: "Metalation of Biginelli Compounds. A General Unprecedented Route to C-6 Functionalized 4-Aryl-3,4-dihydropyrimidinones", JOURNAL OF ORGANIC CHEMISTRY , 70(15), 6114-6117 CODEN: JOCEAH; ISSN: 0022-3263, 2005, XP002388295
Download PDF:
Previous Patent: TARGET VALIDATION ASSAY
Next Patent: METHODS AND APPARATUS PROVIDING SECURITY TO COMPUTER SYSTEMS AND NETWORKS
Next Patent: METHODS AND APPARATUS PROVIDING SECURITY TO COMPUTER SYSTEMS AND NETWORKS