Derivatives of 1-(substituted sulfonyl)-2-aminoimidazoline as antitumor and antiproliferative agents
OwnerStanislaw Wieslaw Pikul, Wieslaw Marek Cholodyinventors
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Abstract
The invention provides novel, water-soluble 2-aminoimidazoline derivatives having general Formula (I) as well as some precursors of Formula (I), which are very potent inducers of G2/M cell cycle arrest. In treated tumor cells, compounds of Formula (I) give gene expression profile distinct from known antimitotic agents. The invention also provides methods for preparing the compounds, and methods of using the compounds for the treatment of cancer or other mammalian diseases characterized by undesirably high levels of cell proliferation. The compounds of the invention are also expected to have utility as research tools.
Claims16
A method of treating a hyperproliferative disorder in a mammal, wherein the hyperproliferative disorder is colorectal cancer, ovarian cancer, liver cancer or lung cancer, the method comprising administering to said mammal a therapeutically effective amount of a compound of Formula (I):
- wherein:
- R1 is
- (a) a hydrogen atom;
- (b) a substituted or unsubstituted alkyl;
- (c) a substituted or unsubstituted aryl or heteroaryl;
- (d) if R1 is not H, its configuration may be either S or R;
- R2 is
- (a) a substituted or unsubstituted alkyl;
- (b) a substituted or unsubstituted phenyl;
- (c) a 5- or 6-membered, optionally substituted, saturated or unsaturated heterocyclic group having from one to three heteroatoms selected from nitrogen, oxygen and sulfur;
- (d) a saturated or unsaturated fused ring carbocyclic group, optionally substituted, having from 8 to 10 ring atoms;
- (e) a saturated or unsaturated fused ring heterocyclic group, optionally substituted, having from 8 to 10 ring atoms including one to three heteroatoms selected from nitrogen, oxygen and sulfur;
- X is a hydrogen atom, carbonyl, thiocarbonyl or imine.
- If X is a hydrogen atom then R3 is null.
- If X is not hydrogen then R3 is:
- (a) a substituted or unsubstituted linear, branched or cyclic alkyl which additionally can be connected to an aromatic or heterocyclic moiety,
- (b) a substituted or unsubstituted phenyl,
- (c) a 5- or 6-membered, saturated or unsaturated heterocyclic group, optionally substituted, having from one to three heteroatoms selected from nitrogen, oxygen and sulfur;
- (d) NR′(CH2)nR″ where
- R′ is hydrogen or alkyl,
- n is 0-3,
- R″ is unsubstituted or substituted alkyl, cycloalkyl, phenyl, benzyl, a 5- or 6-membered, optionally substituted saturated or unsaturated heterocyclic group having from one to three heteroatoms selected from nitrogen, oxygen and sulfur, and
- R′ and R″ can be connected or not,
- (e) O(CH2)nR″ or S(CH2)nR″ where R″ and n are as defined above,
- or a tautomer, pharmaceutically acceptable salt, hydrate, or solvate thereof.
Dependencies are inferred from the claim text.