Tricyclic compounds having antimitotic and/or antitumor activity and methods of use thereof

A method of treating a patient diagnosed with cancer comprising administering to the patient a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt of a compound of Formula I:

• wherein both B and C rings may be completely or partially saturated or unsaturated with respect to bonds 4a-8a, 5-6 and 7-8;
• the C ring may have an R4 attached to the C ring at positions 5, 6, 7 or 8, or a combination of one or more of these positions depending on the saturation level of the C ring and wherein R4 may be the same or different when attached to a plurality of the 5, 6, 7, or 8 positions of the C ring;
• R1 and R2 each independently is one of (a) a hydrogen (H), (b) an alkyl having from one to ten carbon atoms and having a straight or branched configuration, and wherein the alkyl is partially or completely saturated, or a substituted alkyl having from one to ten carbon atoms, (c) a cycloalkyl having from three to ten carbon atoms, or a substituted cycloalkyl having from three to ten carbon atoms, (d) an alkylcycloalkyl, or a substituted alkylcycloalkyl, (e) an aryl, or a substituted aryl, (f) an alkylaryl, or a substituted alkylaryl (g) a heteroaryl, or a substituted heteroaryl, (h) an alkylheteroaryl, or a substituted alkylheteroaryl, (i) an aromatic, or a substituted aromatic, and (j) a heteroaromatic, or a substituted heteroaromatic, and wherein each substituent of any said substituted group is the same or different and is selected from the group consisting of a straight or branched alkyl, alkenyl, or alkynl, a cyclic or alicyclic group having from one to six carbon atoms, a heterocyclic group having from one to six carbon atoms, an alkoxy group, an aryloxy group, an alkyloxyaryloxy group, an aryl group, an amine, a halogen, a phenol, a naphthalene, a piperidine, a pyrrole, a ketone, a methylalkyl ketone, and a trifluoromethyl ketone, and wherein each of said substituents may itself be substituted, and wherein any of said substituents may be optionally attached by a CH2 bridge, and wherein the substituent may be optionally partially or completely saturated or unsaturated when it is not represented by said halogen;
• wherein at least one of R1 and R2 is an alkyl having from one to four carbon atoms and having a straight or branched configuration and wherein the alkyl is partially or completely saturated, or a substituted alkyl having from one to four carbon atoms;
• R1 and R2 are the same or different with the exception that R1 and R2 may not each be hydrogen at the same time;
• R3 is one of (a) a hydrogen (H), (b) a halogen, (c) an alkyl having from one to ten carbon atoms and having a straight or a branched configuration, and wherein the alkyl is partially or completely saturated;
• (d) an NH2, (e) an NHR7, (f) an NR7R8, (g) an OH, (h) an OR, (i) an SH, and (j) an SR, and wherein R is one of R1, and wherein R7 and R8 may be the same or different and are one of R1;
• R4 is one of (a) R1, (b) a halogen, (c) a mono-, di-, tri- or tetra-substituted alkyl, and (d) an alkyloxy, and wherein R1 is H or a lower alkyl and R2 is H or a lower alkyl then R4 is one of (a) a NR6R7, (b) a SR6, (c) a OR6, and (d) a CHR6R7, wherein R6 and R7 are one of R1 and R2, and R6 and R7 may be the same or different when said C ring is completely unsaturated and R6 and R7 are the same when said C ring is completely or partially saturated;
• X is an oxygen (O;
• Y is one of (a) a nitrogen (N), (b) an oxygen (O), (c) a sulfur (S), and (d) a CR6, wherein R6 is one of R1 and R3, and wherein when Y is O or S then either R1 or R2 is absent;
• wherein when said C ring is completely unsaturated and X is an oxygen (O), and Y is a nitrogen (N), then (a) when R1 is an alkyl having from one to four carbon atoms, an alkoxy having from one to four carbon atoms, or a monoalkylamino having from one to four carbon atoms, then R2 does not contain a phenyl;
• and (b) when R2 is an alkyl having from one to four carbon atoms, an alkoxy having from one to four carbon atoms, or a monoalkylamino having from one to four carbon atoms, then R1 does not contain a phenyl;
• and
• wherein when said C ring is completely unsaturated and X is an oxygen (O), and Y is an oxygen (O) or a sulfur (S), then (a) R1 is not an alkyl having from one to four carbon atoms substituted with a phenyl when R2 is absent;
• and (b) R2 is not an alkyl having from one to four carbon atoms substituted with a phenyl when R1 is absent, for achieving a therapeutic response.

A method for inhibiting the mitosis of one or more cancerous cells comprising subjecting one or more live cancerous cells to a mitotic inhibitory acceptable amount of a compound of Formula I, or a pharmaceutical salt or hydrate of the compound of Formula I:

• wherein both B and C rings may be completely or partially saturated or unsaturated with respect to bonds 4a-8a, and completely saturated with respect to bonds 5-6 and 7-8;
• the C ring may have an R4 attached to the C ring at positions 5, 6, 7 or 8, or a combination of one or more of these positions depending on the saturation level of the C ring and wherein R4 may be the same or different when attached to a plurality of the 5, 6, 7, or 8 positions of the C ring;
• R1 and R2 each independently is one of (a) a hydrogen (H), (b) an alkyl having from one to ten carbon atoms and having a straight or branched configuration, and wherein the alkyl is partially or completely saturated, or a substituted alkyl having from one to ten carbon atoms, (c) a cycloalkyl having from three to ten carbon atoms, or a substituted cycloalkyl having from three to ten carbon atoms, (d) an alkylcycloalkyl, or a substituted alkylcycloalkyl, (e) an aryl, or a substituted aryl, (f) an alkylaryl, or a substituted alkylaryl (g) a heteroaryl, or a substituted heteroaryl, (h) an alkylheteroaryl, or a substituted alkylheteroaryl, (i) an aromatic, or a substituted aromatic, and (j) a heteroaromatic, or a substituted heteroaromatic, and wherein each substituent of any said substituted group is the same or different and is selected from the group consisting of a straight or branched alkyl, alkenyl, or alkynl, a cyclic or alicyclic group having from one to six carbon atoms, a heterocyclic group having from one to six carbon atoms, an alkoxy group, an aryloxy group, an alkyloxyaryloxy group, an aryl group, an amine, a halogen, a phenol, a naphthalene, a piperidine, a pyrrole, a ketone, a methylalkyl ketone, and a trifluoromethyl ketone, and wherein each of said substituents may itself be substituted, and wherein any of said substituents may be optionally attached by a CH2 bridge, and wherein the substituent may be optionally partially or completely saturated or unsaturated when it is not represented by said halogen;
• R1 and R2 are the same or different with the exception that R1 and R2 may not each be hydrogen at the same time;
• R3 is one of (a) a hydrogen (H), (b) a halogen, (c) an alkyl having from one to ten carbon atoms and having a straight or a branched configuration, and wherein the alkyl is partially or completely saturated;
• (d) an NH2, (e) an NHR7, (f) an NR7R8, (g) an OH, (h) an OR, (i) an SH, and (j) an SR, and wherein R is one of R1, and wherein R7 and R8 may be the same or different and are one of R1;
• R4 is one of (a) R1, (b) a halogen, (c) a mono-, di-, tri- or tetra-substituted alkyl, and (d) an alkyloxy, and wherein R1 is H or a lower alkyl and R2 is H or a lower alkyl then R4 is one of (a) a NR6R7, (b) a SR6, (c) a OR6, and (d) a CHR6R7, wherein R6 and R7 may be the same or different and comprise are one of R1;
• X is an oxygen (O;
• and
• Y is one of (a) a nitrogen (N), (b) an oxygen (O), (c) a sulfur (S), and (d) a CR6, wherein R6 is one of R1 and R3, and wherein when Y is O or S then R2 is absent, for achieving inhibition of mitosis of said cancerous cell(s).