Tricyclic derivatives and their use

Colchicine derivative represented by the formula (II) and pharmaceutically acceptable salts thereof:

• wherein:
• when R1 is N(R5)C(X1)—A, R2 is hydrogen, X2R6, or X2(O)n1R6;
• R3 and R4 are independently hydrogen, a methyl group, or a lower straight chain or branched alkyl, wherein R5 and R6 are independently hydrogen, or a lower straight chain or branched alkyl;
• X1 and X2 are independently O or S;
• n1 is an integer of 1 or 2;
• and A is selected from the group represented by the following formula:
• wherein R7 is a phenyl, a C1 to C3 straight chain or branched alkyl, a C1 to C3 straight chain or branched alkoxy, halogen selected from F, Cl, Br or I, a nitro, or a cyano group;
• R8 is hydrogen, —ONO2, halogen selected from F, Cl, Br, or I;
• n2 is an integer from 1 to 3.

A compound selected from the group consisting of:

• 2-Fluoro-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Fluoro-5-bromomethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Chloro-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Chloro-5-chloromethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Iodo-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Cyano-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Bromo-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Phenyl-3-nitrooxymethyl-N-(1,2,3,-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Iodo-3-methyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Iodo-3-methyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Cyano-3-methyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Fluoro-5-methyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Nitro-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 3-Methyl-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Methoxy-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Chloro-3-methyl-N-(3,9,10,11-tetramethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl)-benzamide
• 2-Chloro-N-(3-methanesulfonyl-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl)-3-methyl-benzamide;
• 2-Chloro-3-methyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-thioxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Fluoro-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Fluoro-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Chloro-5-methyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Chloro-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Chloro-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Bromo-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Bromo-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Iodo-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Iodo-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Nitro-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Nitro-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 2-Cyano-5-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Cyano-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Nitrooxymethyl-biphenyl-2-carboxylic acid (1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-amide;
• 2-Nitrooxymethyl-biphenyl-4-carboxylic acid (1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-amide;
• 2-Methoxy-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• 4-Methoxy-3-nitrooxymethyl-N-(1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[α]heptalen-7-yl)-benzamide;
• or pharmaceutically acceptable salts thereof.