http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-040995-A1

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filingDate 2003-08-15-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2005-04-27-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber AR-040995-A1
titleOfInvention COMBINATION THERAPY FOR HYPERPROLIFERATIVE DISEASES
abstract Method to treat hyperproliferative diseases. More particularly, the present refers to a method for treating hyperproliferative diseases, such as cancer, which comprises the operation of administering to a mammal in need of such treatment, either simultaneously, or successively, (i) a therapeutically effective amount of a derivative of taxane, a platinum coordination complex selected from the group consisting of carboplatin, tetraplatin, and topotecan, a nucleoside analog compound selected from the group consisting of gencitabine hydrochloride and 5-FU, an anthracycline, a topoisomerase inhibitor selected from the group consisting of etoposide, teniposide, ancacrine, topotecan and Camptosar (R), an aromatase inhibitor; and (ii) a therapeutically effective amount of an isothiazole derivative. Combinations of the present may optionally include an antihypertensive agent. This present also refers to pharmaceutical compositions useful in the treatment of hyperproliferative diseases in mammals, which contain such combinations. The present also refers to systems that have a first behavior with a compound of formula (1), and a second compartment containing a taxane derivative, a platinum coordination complex, a nucleoside analog compound, an anthracycline, topoisomerase or an aromatase inhibitor, and a third compartment containing an antihypertensive agent. Claim 1: A method of treating a hyperproliferative disorder in a mammal, characterized in that it comprises administering to said mammal in need of said treatment, either simultaneously or successively, (i) a therapeutically effective amount of a taxane derivative, a platinum coordination complex selected from the group consisting of carboplatin, tetraplatin and topotecan, a nucleoside-like compound selected from the group consisting of gencitabine hydrochloride and 5-FU, an anthracycline, a topoisomere inhibitor selected from the group consisting of etoposide, teniposide, ansacrine, topotecan and Camptosar (R), and an aromatase inhibitor; and (ii) a therapeutically effective amount of a compound of formula (1) or a pharmaceutically acceptable salt, prodrug or solvate thereof, formula in which: X1 is O or S; R1 is H, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, -C (O) (C1-10 alkyl), - (CH2) t (C6-10 aryl), - (CH2) t (heterocycle 4-10 members), -C (O) (CH2) t (C6-10 aryl) or -C (O) (CH2) (5-10 member heterocycle), in which t is an integer of 0 to 5; alkyl group that optionally includes 1 or 2 hetero-strains selected from O, S and -N (R6) - with the proviso that two O atoms, two S atoms or one O atom and one S atom are not directly linked between yes; aryl and heterocyclic R1 groups that are optionally fused with a C6-10 aryl group, a C5-8 saturated cyclic group or a 5-10 membered heterocyclic group; 1 or 2 carbon atoms of the preceding heterocyclic moieties being optionally substituted with an oxo moiety (= O); residues - (CH2) t- of the preceding R1 groups, in which t is an integer from 2 to 5, which optionally include a double or triple carbon-carbon bond; and preceding R1 groups which, except H, are optionally substituted with 1 to 3 R4 groups; R2 is selected from the list of substituents provided in the definition of R1, -SO2 (CH2) t (C6-10 aryl) m -SO2 (CH2) t (5-10 membered heterocycle) and -OR5, where t is a number integer varying from 0 to 5, moieties - (CH2) t- of the preceding R2 groups, in which t is an integer from 2 to 5, optionally including a double or triple carbon-carbon bond, and preceding R2 groups which are optionally substituted with 1 to R4 groups; or R1 and R2 may be taken together with the nitrogen to which each is attached to form a 4-10 membered saturated monocyclic or polycyclic ring or a 5-10 membered heteroaryl ring, saturated and heteroaryl rings optionally including 1 or 2 heteroatoms selected from O, S and -N (R6) - in addition to the nitrogen to which R1 and R2 are attached, said -N (R6) - optionally = N- or -N = when R1 and R2 are taken together as said group heteroaryl, saturated ring that may optionally be partially unsaturated by including 1 or 2 carbon-carbon double bonds, and saturated and heteroaryl rings which, including the R6 group of said -N (R6) -, are optionally substituted with 1 to 3 groups R4; R3 is H, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, - (CH2) t (C6-10 aryl) or - (CH2) t (5-10 membered heterocycle, where t is an integer number of 0 to 5; alkyl group that optionally includes 1 or 2 hetero-strains selected from O, S and -N (R6) - with the proviso that two O atoms, two S atoms or one O atom and one S atom do not are directly linked to each other; R3 heterocyclic aryl groups that are optionally fused with a C610 aryl group, a C5-8 saturated cyclic group or a 5-10 membered heterocyclic group; 1 or 2 carbon atoms of the optionally preceding heterocyclic moieties being optionally substituted with an oxo moiety (= O); moieties - (CH2) t- of the preceding R3 groups, in which t is an integer from 2 to 5, optionally including a double or triple carbon-carbon bond; and groups R3 precedents that are optionally substituted with 1 to 5 R4 groups; each R4 is independently selected from C1-10 alkyl, alkenyl C2-10, C2-10 alkynyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, -OR5, -C (O) R5, -C (O) OR5, NR6C (O) OR5, -OC8 (O) R5 , -NR6SO2R5, -SO2NR5R6, -NR6-C (O) R5, C (O) NR5R6, -NR5R6, -S (O) JR7 in which j is an integer that varies from 0 to 2, -SO3H, -NR5 (CR6R7) tOR6, - (CH2) t (C6-10 aryl), -SO2 (CH2) t (C6-10 aryl), -S (CH2) t (C6-10 aryl), -O- (CH2) t (C6-10 aryl), - (CH2) t (5-10 membered heterocycle) and - (CR6-R7) mOR6, where m is an integer from 1 to 5 and t is a number from 0 to 5; alkyl group optionally containing 1 or 2 hetero-strains selected from O, S and -N (R6) - with the proviso that two O atoms, two S atoms or one O atom and one S atom are not directly linked to each other ; R4 aryl and heterocyclic groups that are optionally fused with a C6-19 aryl group, a C5-8 saturated cyclic group or a 5-10 membered heterocyclic group; 1 or 2 carbon atoms of the preceding heterocyclic moieties being optionally substituted with an oxo moiety (= O); and alkyl, aryl and heterocycle moieties of the preceding R4 groups that are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, -NR6-SO2R5, -SO2NR5R6, -C (O) R5, -C (O) OR5, -OC (O) R5, -NR6C (O) R5,.-C (O) NR5R6, NR5R6, - (CR6R7) mOR6 in which m is an integer from 1 to 5, -OR5 and the substituents listed in the definition of R5; each R5 is independently selected from H, C1-10 alkyl, - (CH2) t- (C6-10 aryl) and - (CH2) t (5-10 membered heterocycle), in which t is an integer of 0 to 5; alkyl group that optionally includes 1 or 2 hetero-strains selected from O, S and -N (R6) - with the proviso that two O atoms, two S atoms or one O atom and one S atom are not directly linked between yes; R5 aryl and heterocyclic groups that are optionally fused with a C6-10 aryl group, a C58 saturated cyclic group or a 5-10 membered heterocyclic group; and the preceding R5 substituents, except H, being optionally substituted with 1 to 3 substituents independently selected from halogens, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, -C (O) R6, -C (O) OR6, -CO ( O) R6, -NR6C (O) R7, -C (O) NR6R7, -NR6R7, hydroxyl, C1-6 alkyl and C1-6 alkoxy; and each of R6 and R7 is independently H or C1-6 alkyl.
priorityDate 2002-08-19-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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