Nitrogen-containing tricyclic compounds and drugs containing the same

A nitrogen-containing tricyclic compound represented by the following formula (I), a hydrate thereof or a pharmacologically acceptable salt thereof:

• wherein R1, R2, R3, R4, R5, R6, R7 and R8 are the same or different from each other and each represents hydrogen, hydroxy, cyano, nitro, optionally substituted carbamoyl, halogeno, optionally halogenated lower alkyl, optionally substituted cycloalkyl, optionally halogenated lower alkoxy, acyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, cycloalkylalkyl, hydroxylated alkyl, alkoxyalkyl, optionally protected carboxyalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, cyanoalkyl, acylalkyl, optionally substituted carbamoylalkyl, optionally halogenated alkenyl, hydroxyalkenyl, alkoxyalkenyl, optionally protected carboxyalkenyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, cyanoalkenyl, acylalkenyl, optionally substituted carbamoylalkenyl, optionally halogenated alkynyl, hydroxyalkynyl, alkoxyalkynyl, optionally protected carboxyalkynyl, optionally substituted arylalkynyl, optionally substituted heteoarylalkynyl, cyanoalkynyl, acylalkynyl, optionally substituted carbamoyalkynyl, hydroxyalkoxy, alkoxyalkoxy, optionally protected carboxyalkoxy, optionally substituted heteroarylalkoxy, —A—NR9R10 (wherein A represents optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene or a single bond;
• and R9 and R10 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl, optionally substituted aryl or acyl, or R9 and R10 may form together with the nitrogen atom to which they are bonded a ring optionally having additional nitrogen, oxygen or sulfur), or
• (wherein B represents optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene or a single bond;
• R11 represents optionallyy halogenated lower alkyl or amino optionally substituted by lower alkyl;
• and x represents an integer of from 0 to 2);
• provided that two of R1, R2, R3, R4, R5, R6, R7, and R8 adjacent to each other may form together with the carbon atom to which they are bonded a ring optionally containing oxygen, sulfur or nitrogen and optionally substituted;
• Z represents
• (wherein y represents an integer of from 0 to 2), wherein R12, R13, R14, R15, R16 and R17 are the same or different from each other and each represents hydrogen, optionally substituted carbamoyl, optionally halogenated lower alkyl, optionally substituted cycloalkyl, acyl, optionally halogenated lower alkylsulfonyl, optionally substituted arylsulfonyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, cycloalkylalkyl, hydroxylated alkyl, alkoxyalkyl, optionally protected carboxyalkyl, optionally substituted arylakyl, optionally substituted heteroarylalkyl, cyanoalkyl, acylalkyl, optionally substituted carbamoylalkyl, optionally halogenated alkenyl, hydroxyalkenyl, alkoxyalkenyl, optionally protected carboxyalkenyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, cyanoalkenyl, acylalkenyl, optionally substituted carbamoyalkenyl, optionally halogenated alkynyl, hydroxyalkynyl, alkoxyalkynyl, optionally protected carboxyalkynyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkynyl, cyanoalkynyl, acylalkynyl, optionally substituted carbamoylalkynyl, —W—NR18R19 (wherein W represents optionally branched alkylene, optionally branched alkenylene, optionally branched alkynylene or a single bond;
• R18 and R19 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl or acyl, or R18 and R19 may form together with the nitrogen atom to which they are bonded a ring optionally containing additional nitrogen, oxygen or sulfur));
• D represents optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene or
• (wherein m and 1 are each an integer of from 0 to 6;
• the ring A means an optionally substituted hydrocarbon ring or an optionally substituted heterocycle);
• and
• Q represents optionally substituted carbamoyl, acyl, acylalkyl, optionally protected carboxyl, optionally substituted heteroaryl, or —NR20R21 (wherein R20 and R21 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl, optionally halogenated lower alkoxy, hydroxylated alkyl, alkyl, alkoxyalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted arylalkoxy, optionally substituted heteroaryloxy, optionally substituted heteroarylalkoxy, optionally protected carboxyalkyl, acyl, optionally substituted acylalkyl, optionally substituted acylamino, optionally substituted acylaminoalkyl, optionally substituted carbamoylalkyl, optionally substituted aminoalkyl, cyanoalkyl, acylalkyl, cycloalkyl, cycloalkylalkyl or amindino optionally substituted by lower alkyl, or R20 and R21 may for together with the nitrogen atom to which they are bonded an optionally substituted 3- to 8-membered ring which may have, as its ring-member other than carbon, at least one member selected from the group consisting of nitrogen, sulfur, oxygen and —NR22 (wherein R22 represents hydrogen, optionally halogenated lower alkyl, acyl, optionally substituted acylalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or —S(O)s—(Y)u—R23 (wherein R23 represents hydrogen, optionally halogenated lower alkyl or optionally substituted aryl;
• Y represents methylene;
• s is an integer of from 0 to 2;
• and u is 0 or 1)))
• provided that the following compounds are excluded:
• (1) the compound where R5 and R6 are both hydrogen atoms;
• (2) the compound where Z is
• (wherein y is an integer of from 0 to 2);
• R5 is fluoro;
• and R6 is fluoro or trifluoromethyl;
• (3) the compound where Z is
• (wherein y is an integer of from 0 to 2);
• R5 is carboxy;
• and R6 is chloro;
• (4) the compound where (i) one of R1, R2, R3, R4, R5, R6, R7 and R8 is an optionally substituted heteroaryl or an optionally substituted heteroarylalkyl and (ii) D is an optionally substituted alkylene,
• (5) the compound where (i) one of R1, R2, R R4, R5, R6, R7 and R8 is an optionally substituted heteroaryl or an optionally substituted heteroarylalkyl and (ii) A is an optionally substituted heterocycle;
• and
• (6) the compound where (i) R3 or R6 is an optionally protected carboxyl, an acyl, an optionally protected carboxyalkyl or an acylalkyl, R1, R2, R4 , R5, R7 and R8 are hydrogen and (ii) D is an optionally substituted alkylene.