Tricyclic fused heterocycle compounds, process for preparing the same and use thereof

A method of preparing a compound represented by formula (1),

• wherein
• when the X—Y bond is a single bond, X and Y are independently selected from the group consisting of:
• CW1W2 wherein W1 and W2 are independently selected from the group consisting of one of a hydrogen atom, a halogen, a hydroxyl group, a lower alkyl group, a substituted lower alkyl group, a lower alkoxy group, a cycloalkyl group and a cycloalkenyl group,
• C═O, and
• C═NOW3 wherein W3 is a hydrogen atom or a lower alkyl group;
• when the X—Y bond is a double bond, X and Y are each independently CW4 wherein W4 is any one of a hydrogen atom, a halogen, a hydroxyl group, a lower alkyl group, a substituted lower alkyl group, a lower alkoxy group or an acyloxy group;
• Z is O;
• U is C;
• R1 to R4, are independently selected from the group consisting of a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a cycloalkyl group, a substituted cycloalkyl group, a lower alkenyl group, a substituted lower alkenyl group, a lower alkynyl group, a substituted lower alkynyl group, a halogen, a lower alkylcarbonyl group, a substituted lower alkylcarbonyl group, a trihalomethyl group, V1W5, a nitro group, an amino group, a substituted amino group, a cyano group, an acyl group, an acylamino group, a substituted acyl group, a substituted acylamino group, an aromatic ring, a substituted aromatic ring, a heterocycle and a substituted heterocycle wherein
• V1 is any one of O, S, S═O or SO2,
• W5 is any one of a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkylcarbonyl group and a substituted lower alkylcarbonyl group, an acyloxy group or a trihalomethyl group, and
• R5 to R8 are independently selected from the group consisting of a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, a substituted lower alkenyl group, a lower alkynyl group, a substituted lower alkynyl group, a halogen, a lower alkylcarbonyl group, a substituted lower alkylcarbonyl group, a trihalomethyl group, V2W7, a nitro group, an amino group, a substituted amino group, an acylamino group, an aromatic ring, a substituted aromatic ring, a heterocycle and a substituted heterocycle;
• wherein
• V2 is one of O, S, S═O or SO2,
• W7 is one of a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkylcarbonyl group, a substituted lower alkylcarbonyl group or a trihalomethyl group,
• wherein:
• W0 is any one selected from the group consisting of a lower alkyl group and a substituted lower alkyl group;
• when X is CHW0, CW0W0 or CW0 at least one of R5 to R8 is a hydroxyl group, provided that at least one of R5, R7 or R8 is a hydroxy group when the X—Y bond is CH(C2H5)CO and R6 is a hydroxyl group and
• when X is other than CHW0, CW0W0 or CW0 at least one of R5 to R8 is a hydroxyl group and, at the same time, at least one of the other R5 to R8 is a group of OR wherein
• R is any one selected from the group consisting of a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkylcarbonyl group and a substituted lower alkylsilyl group;
• and
• when the X—Y is CH2CH2, CHBrCH2, CH2CO, CHBrCO, CH═CH, CH═COCOCH3 or CH═COCH3,
• at least one of R1 to R4 is an aromatic ring, a substituted aromatic ring, a heterocycle or a substituted heterocycle provided that when both R6 and R7 are hydroxyl groups, any one of R1 to R4 is not a phenyl group;
• or
• at least one of R1 to R4 is SW8 or S(O)W9 wherein W8 and W9 independently are a lower alkyl group or a substituted lower alkyl group provided that R7 is not a hydrogen atom when Z is O;
• or
• R2 is either a lower alkyl group or a substituted lower alkyl group and, at the same time, R8 is a hydroxyl group provided that the number of carbon atoms of the lower alkyl group is 3 or more when Z is O;
• or
• at least one of R1 to R4 is a lower alkylcarbonyl group provided that the number of carbon atoms of the lower alkyl group is 3 or more, a cycloalkylcarbonyl group or a cycloalkenylcarbonyl group and, at the same time,
• R8 is a hydroxyl group;
• or
• at least one of R1 to R4 is a cyano group;
• or
• at least one of R1 to R4 is —C(═NOR)CH3 wherein R is a hydrogen atom or a lower alkyl group, an optical isomer thereof, a conjugate thereof or a pharmaceutically acceptable salt thereof,
• which comprises, in any order, the reaction steps of (1) bonding a ring A:
• to a ring C:
• by the Ullman reaction to obtain a compound of the formula 1A:
• and then subjecting the formula 1A compound to a Friedel-Crafts reaction or a photoreaction to obtain a compound of formula:
• (2) bonding a ring A:
• to a ring C:
• by the Friedel-Crafts reaction or photoreaction to obtain a compound of the formula 1B:
• and then subjecting the formula 1B compound to an Ullman reaction to obtain a compound of formula:
• wherein:
• each Q is independently selected from hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a cycloalkyl group, a substituted cycloalkyl group, a lower alkenyl group, a substituted lower alkenyl group, a lower alkynyl group, a substituted lower alkynyl group, a halogen, a lower alkylcarbonyl group, a substituted lower alkylcarbonyl group, a trihalomethyl group, V1W5, a nitro group, an amino group, a substituted amino group, a cyano group, an acyl group, an acylamino group, a substituted acyl group, a substituted acylamino group, an aromatic ring, a substituted aromatic ring, a heterocycle and a substituted heterocycle;
• each S is independently selected from the group consisting of a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, a substituted lower alkenyl group, a lower alkynyl group, a substituted lower alkynyl group, a halogen, a lower alkylcarbonyl group, a substituted lower alkylcarbonyl group, a trihalomethyl group, V2W7, a nitro group, an amino group, a substituted amino group, an acylamino group, an aromatic ring, a substituted aromatic ring, a heterocycle and a substituted heterocycle;
• W is —CH2CO2H;
• or W is a substituent that can be converted to —CH2CO2H by a conversion reaction, a carbon atom increasing reaction, or by a reaction of deprotection;
• U is C;
• one of X and Y is a leaving group and the other is a nucleophilic group;
• and
• Z is O.