US 7,320,981 B2 | ||
Variolin derivatives as anti-cancer agents | ||
Jonathan Charles Morris, Christchurch (New Zealand); Regan James Anderson, Christchurch (New Zealand); Modesto Remuiñán, Madrid (Spain); and Ignacio Manzanares, Madrid (Spain) | ||
Assigned to Pharma Mar, S.A., Madrid (Spain) | ||
Appl. No. 10/332,562 PCT Filed Jul. 11, 2001, PCT No. PCT/GB01/03111 § 371(c)(1), (2), (4) Date Jun. 25, 2003, PCT Pub. No. WO02/04447, PCT Pub. Date Jan. 17, 2002. |
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Claims priority of application No. 0017055.5 (GB), filed on Jul. 11, 2000; and application No. 0030689.4 (GB), filed on Dec. 15, 2000. | ||
Prior Publication US 2005/0014778 A1, Jan. 20, 2005 | ||
Int. Cl. C07D 471/14 (2006.01); A61K 31/505 (2006.01) |
U.S. Cl. 514—267 [544/250] | 45 Claims |
1. A compound of formula (I):
![]() R1 and R2 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO2R′, NO2, NH2, NHR′, N(R′)2, NHCOR′, N(COR′)2, NHSO2R′, CN, halogen, C(═O)H, C(═O)R′, CO2H, CO2R′, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic;
and
R3 is selected from the group consisting of OH and OMe;
wherein each R′ group is independently selected from the group consisting of OH, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted arylalkenyl
and substituted or unsubstituted heteroaromatic,
and wherein when the group R1 or R2 is a group of formula N(R′)2 or N(COR′)2, each of the R′ groups may be the same or different, or the two R′ groups, together with the nitrogen atom to which they
are attached, may form a 5-14 membered heterocyclic ring;
the aryl group and the aryl moiety of the aralkyl and arylalkenyl group is a carbocyclic aryl group having from 6 to 14 carbon
atoms in a carbocyclic ring or two or more fused rings;
the aralkyl group is a C1-C6 alkyl group which is substituted by an aryl group as defined above;
the arylalkenyl group is a C2-C6 alkenyl group which is substituted by an aryl group as defined above;
the heteroaromatic group is a heterocyclic aromatic group having from 5 to 14 ring atoms in one ring or two or more fused
rings of which at least one ring atom is selected from the group consisting of nitrogen, oxygen and sulphur, and such a heterocyclic
aromatic group fused with an aryl group as defined above;
the substituents on the aryl and heteroaromatic groups and the aryl moiety of the aralkyl and arylalkenyl groups are selected
from the group consisting of C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, NH2, C1-C6 alkylamino, di(C1-C6 alkyl)amino, C1-C4 alkanoylamino, di(C1-C4 alkanoyl)amino, NO2, CN and halogen;
and wherein one or more of the tertiary amine nitrogen atoms of formula (I) is optionally quaternised,
or a pharmaceutically acceptable salt thereof,
with the exception of the compounds wherein:
R1 and R2 are amino and R3 is hydroxy.
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