Hydroxamic acid derivatives

A compound represented by the formula (1), or a pharmaceutically acceptable salt thereof:

• wherein
• X is a group represented by the formula:
• where A1 is ortho-phenylene or monocyclic ortho-heteroarylene;
• and R8 and R9 are independently hydrogen, or substituents of the ortho-phenylene and the ortho-heteroarylene
• Y1 is —O—, —S—, —S(O)— or —S(O)2—;
• Y2 is —O— or —S—;
• one of R1 and R3 is —(CHR4)n—(CR5R6)—CO—NHOH;
• the other of R1 and R3 is hydrogen, optionally substituted alkyl, or optionally substituted cycloalkyl;
• R2 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted hetero-cycloalkyl;
• or R2 and R3 may be taken together to be optionally substituted C1-C10 alkylidene;
• R4, R5 and R6 are independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or R5 may be joined with R4 or R6 to form a ring with the carbon atom which they attach, wherein said ring is optionally substituted cycloalkane or optionally substituted heterocycloalkane;
• n is an integer of 0 to 4;
• wherein
• said cycloalkyl is C3-8 cycloalkyl containing a 0-2 carbonyl group;
• said heterocycloalkyl is 5- or 6-membered heterocycloalkyl containing 1 to 5 atoms selected independently from nitrogen atoms, sulfur atoms, and oxygen atoms, wherein said sulfur atoms may be oxidized to form sulfoxide or sulfone;
• said heteroaryl is mono or bicyclic 5- or 6-membered heteroaryl containing 1 to 5 atoms selected independently from nitrogen atoms, sulfur atoms, and oxygen atoms;
• said ortho-heteroarylene is mono or bicyclic 5- or 6-membered ortho-heteroarylene containing 1 to 3 atoms selected independently from nitrogen atoms, sulfur atoms, and oxygen atoms;
• said cycloalkane is C3-8 cycloalkane containing a 0-2 carbonyl group;
• said heterocycloalkane is 5- or 6-membered heterocycloalkane containing 1 to 5 atoms selected independently from nitrogen atoms, sulfur atoms, and oxygen atoms, wherein said sulfur atoms may be oxidized to form sulfoxide or sulfone;
• a substituent of said substituted aryl and said substituted heteroaryl, and a substituent represented by R8 and R9 are selected from the group consisting of
• halogen;
• alkyl;
• alkenyl;
• alkynyl;
• halogenated alkyl;
• —Z1—Ar3;
• —Z1—Cy1;
• —Z1—N(Q2)Q1;
• —Z1—N(Q2)Ar3;
• —Z1—N(Q2)Cy1;
• —Z1—NQ4—C(NQ3)N(Q2)Q1;
• —Z1—NQ4—C(NQ3)N(Q2)Ar3;
• —Z1—NQ4—C(NQ3)N(Q2)Cy1;
• —Z1—NQ3—CON(Q2)Q1;
• —Z1—NQ3—CON(Q2)Ar3;
• —Z1—NQ3—CON(Q2)Cy1;
• —Z1—NQ2—COOQ1;
• —Z1—NQ2COOAr3;
• —Z1—NQ2COOCy1;
• —Z1—OCON(Q1)Q2;
• —Z1—OCON(Q2)Ar3;
• —Z1—OCON(Q2)Cy1;
• —Z1—OCOOQ1;
• —Z1—OCOOAr3;
• —Z1—OCOOCy1;
• —Z1—NQ2—COQ1;
• —Z1—NQ2COAr3;
• —Z1—NQ2—COCy1;
• —Z1—NQ2—SOQ1;
• —Z1—NQ2—SOAr3;
• —Z1—NQ2—SOCy1;
• —Z1—NQ2—SO2Q1;
• —Z1—NQ2—SO2Ar3;
• —Z1—NQ2—SO2Cy1;
• —Z1—OQ1;
• —Z1—OAr3;
• —Z1—O—Cy1;
• —Z1—OCOQ1;
• —Z1—OCOAr3;
• —Z1—OCOCy1;
• —Z1—COOQ1;
• —Z1—COOAr3;
• —Z1—COOCy1;
• —Z1—CON(Q1)Q2;
• —Z1—CON(Q2)Ar3;
• —Z1—CON(Q2)Cy1;
• —Z1—CON(Q2)OQ1;
• —Z1—CON(Q2)OAr3;
• —Z1—CON(Q2)Cy1;
• —Z1—COQ1;
• —Z1—COAr3;
• —Z1—CO—Cy1;
• —Z1—C(NQ3)N(Q1)Q2;
• —C(NQ3)N(Q2)Ar3;
• —Z1—C(NQ3)N(Q2)Cy1;
• —Z1—SQ1;
• —Z1—SAr3;
• —Z1—S—Cy1;
• —Z1—SOQ1;
• —Z1—SOAr3;
• —Z1—SOCy1;
• —Z1—SO2Q1;
• —Z1—SO2Ar3;
• —Z1—SO2Cy1;
• —Z1—SON(Q1)Q2;
• —Z1—SON(Q2)Ar3;
• —Z1—SON(Q2)Cy1;
• —Z1—SO2N(Q1)Q2;
• —Z1—SO2N(Q2)Ar3;
• —Z1—SO2N(Q2)Cy1;
• —Z1—SO3H;
• —Z1—OSO3H;
• —Z1—NO2;
• —Z1—CN;
• and —CHO;
• wherein
• Z1 is single bond, alkylene, alkenylene or alkynylene;
• Q1, Q2, Q3, Q4 are independently hydrogen, alkyl, alkenyl, or alkynyl, wherein the alkyl, the alkenyl and the alkynyl are optionally substituted by one or more substituents selected from the group consisting of
• halogen;
• —Ar4;
• —Cy2;
• —N(R21)R22;
• —N(R22)Ar4;
• —N(R22)Cy2;
• —NR24—C(NR23)N(R22)R21;
• —NR24—C(NR23)N(R22)Ar4;
• —NR24—C(NR23)N(R22)Cy2;
• —NR23—CON(R22)R21;
• —NR23—CON(R22)Ar4;
• —NR23—CON(R22)Cy2;
• —NR22—COOR21;
• —NR22—COOAr4;
• —NR22—COOCy2;
• —OCON(R22)R21;
• —OCON(R22)Ar4;
• —OCON(R22)Cy2;
• —OCOOR21;
• —OCOOAr4;
• —OCOOCy2;
• —NR22COR21;
• —NR22—COAr4;
• —NR22—COCy2;
• —NR22—SOR21;
• —NR22SOAr4;
• —NR22SOCy2;
• —NR22—SO2R21;
• —NR22—SO2Ar4;
• —NR22—SO2Cy2;
• —OR21;
• —OAr4;
• —OCy2;
• —OCOR21;
• —OCOAr4;
• —OCOCy2;
• —COOR21;
• —COOAr4;
• —COOCy2;
• —CON(R21)R22;
• —CON(R22)Ar4;
• —CON(R22)Cy2;
• —CON(R22)OR21;
• —CON(R22)OAr4;
• —CON(R22)OCy2;
• —COR21;
• —COAr4;
• —COCy2;
• —SR21;
• —SAr4;
• —SCy2;
• —SOR21;
• —SOAr4;
• —SOCy2;
• —SO2R21;
• SO2Ar4;
• —SO2Cy2;
• —SON(R22)R21;
• —SON(R22)Ar4;
• —SON(R22)Cy2;
• —SO2N(R22)R21;
• —SO2N(R22)Ar4;
• —SO2N(R22)Cy2;
• SO3H;
• —OSO3H;
• —NO2;
• —CN;
• and —CHO;
• or Q1 may be joined with Q2 or Q3 to form optionally substituted heterocycloalkane, with the carbon atom with which they attach;
• Ar3 and Ar4 are independently phenyl or heteroaryl, wherein the phenyl and the heteroaryl are optionally substituted by one or two substituents selected from the group consisting of
• halogen;
• alkyl;
• alkenyl;
• alkynyl;
• halogenated alkyl;
• —Z2—N(R25)R26;
• —Z2—NR28—C(NR27)N(R26)R25;
• —Z2—NR27—CON(R26)R25;
• —Z2NR26—COOR25;
• —Z2—OCON(R26)R25;
• —Z2—NR26—COR25;
• —Z2—NR26—SOR25;
• —Z2—NR26—SO2R25;
• —Z2—OR25;
• —Z2COOR25;
• —Z2—OCOR25;
• —Z2—OCOOR25;
• —Z2—CON(R26)R25;
• —Z2—CON(R26)OR25;
• —Z2—COR25;
• —Z2—C(NR27)N(R26)R25;
• —Z2—SR25;
• Z2—SOR25;
• —Z2—SO2R25;
• —Z2SON(R25)R26;
• —Z2—SO2N(R26)R25;
• —Z2—SO3H;
• —Z2—OSO3H;
• —Z2—NO2;
• —Z2—CN;
• —CHO—O—CH2—O—;
• —O—CH2—CH2—O—;
• —O—CH2CH2—, —CH2—CH2—O—CO—, and —CH2—O—CO—,
• wherein
• Z2 is a single bond, alkylene, alkenylene or alkynylene;
• R21, R22, R23, R24, R25, R26, R27, and R28 are independently hydrogen, alkyl, alkenyl, alkynyl, wherein R21 may be joined with R22 or R23 to form heterocycloalkane with the carbon atom with which they attach, or R25 may be joined with R26 or R27 to form heterocycloalkane with the carbon atom with which they attach;
• Cy1 and Cy2 are independently cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, wherein the cycloalkyl, the cycloalkenyl, the heterocycloalkyl, and the heterocycloalkenyl are optionally substituted by one or two substituents which are selected from the same group as the substituents of Ar3 and Ar4;
• a substituent of said substituted alkyl, said substituted alkenyl, said substituted alkynyl, said substituted alkoxy, said substituted alkylthio, said substituted cycloalkyl, said substituted heterocycloalkyl, and said substituted C1-C10 alkylidene is selected from the group consisting of
• halogen;
• —Ar5;
• —Cy3;
• —N(Q5)Q6;
• —N(Q6)Ar5;
• —N(Q6)Cy3;
• —NQ8—C(NQ7)N(Q6)Q5;
• —NQ8—C(NQ7)—N(Q6)Ar5;
• —NQ8—C(NQ7)N(Q6)Cy3;
• —NQ7—CON(Q6)Q5;
• —NQ6—CON(Q5)Ar5;
• —NQ7—CON(Q6)Cy3;
• —NQ7—COOQ6;
• —NQ7—COOAr5;
• —NQ7—COOCy3;
• —OCON(Q6)5;
• —OCON(Q6)Ar5;
• —OCON(Q6)Cy3;
• —NQ6—COQ5;
• —NQ6—COAr5;
• —NQ6—COCy3;
• —NQ6SOQ5;
• —NQ6—SOAr5;
• —NQ6—SOCy3;
• —NQ6—SO2Q5, —NQ6—SO2Ar5;
• —NQ6—SO2Cy3;
• —OQ5;
• —OAr5;
• —OCy3;
• —OCOQ5;
• —OCOAr5;
• —OCOCy3;
• —COOQ5;
• —COOAr5;
• —COOCy3;
• —OCOOQ5;
• —OCOOAr5;
• —OCOOCy3;
• —CON(Q6)Q5;
• —CON(Q6)Ar5;
• —CON(Q6)Cy3;
• —CON(Q6)OQ5;
• —CON(Q6)OAr5;
• —CON(Q6)OCy3;
• —COQ5;
• —COAr5;
• —COCy3;
• —SQ5;
• —SAr5;
• —SCy3;
• —SOQ5;
• —SOAr5;
• —SOCy3;
• —SO2Q5;
• —SO2Ar5;
• —SO2Cy3;
• —SON(Q6)Q5;
• —SON(Q6)Ar5;
• —SON(Q6)Cy3;
• —SO2N(Q6)Q5;
• —SO2N(Q6)Ar5;
• —SO2N(Q6)Cy3;
• —SO3H;
• —NO2;
• and —CN;
• wherein
• Q5, Q6, Q7, and Q8 are independently hydrogen, alkyl, alkenyl and alkynyl wherein the alkyl, the alkenyl and the alkynyl are optionally substituted by one or more substituents selected from the group consisting of
• halogen;
• —Ar6;
• —Cy4;
• —N(R29)R30;
• —N(R30)Ar6;
• —N(R30)Cy4;
• —NR32—C(NR31)N(R30)R29;
• —NR32—C(NR31)N(R30)Ar6;
• —NR32—C(NR31)N(R30)Cy4;
• —NR31—CON(R30)R29;
• —NR31—CON(R30)Ar6;
• —NR31—CON(R30)Cy4;
• —NR30—COOR29;
• —NR30—COOAr6;
• —NR30—COOCy4;
• —OCON(R30)R29;
• —OCON(R30)Ar6;
• —OCON(R30)Cy4;
• —NR30—COR29;
• —NR30—COAr6;
• —NR30COCy4;
• —NR30—SOR29;
• —NR30—SOAr6;
• —NR30—SOCy4;
• —NR30—SO2R29;
• —NR30—SO2Ar6;
• —NR30—SO2Cy4;
• —OR29;
• —OAr6;
• —OCy4;
• —COOR29;
• —COOAr6;
• —COOCy4;
• —OCOR29;
• —COAr5;
• —OCOCy3;
• —OCOOR29;
• —OCOOAr6;
• —Z1—OCOOCy4;
• —CON(R30)R29;
• —CON(R30)Ar6;
• —CON(R30)Cy4;
• —CON(R30)OR29;
• —CON(R30)OAr6;
• —CON(R30)OCy4;
• —COR29;
• —COAr6;
• —COCy4;
• —SR29;
• —SAr6;
• —SCy4;
• —SOR29;
• —SOAr6;
• —SOCy4;
• —SO2R29;
• —SO2Ar6;
• —SO2Cy4;
• —SON(R30)R29;
• —SON(R30)Ar6;
• —SON(R30)Cy4;
• —SO2N(R30)R29;
• —SO2N(R30)Ar6;
• —SO2N(R30)Cy4;
• —SO3H;
• —NO2;
• and —CN;
• or Q5 may be joined with Q6 or Q7 to form heterocycloalkane with the carbon atom with which they attach, wherein
• R29, R30, R31, and R32 are independently hydrogen, alkyl, alkenyl, or alkynyl;
• Ar5 and Ar6 are independently optionally substituted aryl or optionally substituted heteroaryl;
• Cy3 and Cy4 are independently cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, wherein the cycloalkyl, the cycloalkenyl, the heterocycloalkyl, and the heterocycloalkenyl are optionally substituted by one or two substituents which are the same as the substituent of Ar3 or Ar4;
• a substituent of said substituted cycloalkane and said substituted heterocycloalkane is selected from the group consisting of
• halogen;
• —Ar5;
• —Cy3;
• —N(Q5′)Q6′;
• —N(Q6′)Ar5;
• —N(Q6′)Cy3;
• —NQ8′—C(NQ7′)N(Q6′)Q5′;
• —NQ8′—C(NQ7′)N(Q6′)Ar5;
• —NQ8′—C(NQ7′)N(Q6′)Cy3;
• —NQ7′—CON(Q6′)Q5′;
• —NQ6′—CON(Q5′)Ar5;
• —NQ7′—CON(Q6′)Cy3;
• —NQ7′—COOQ6;
• —NQ7′—COOAr5;
• —NQ7′—COOCy3;
• —OCON(Q6′)Q5′;
• —OCON(Q6′)Ar5;
• —OCON(Q6′)Cy3;
• —NQ6′—COQ5′;
• —NQ6′—COAr5;
• —NQ6′—COCy3;
• —NQ6′—SOQ5′;
• —NQ6′—SOAr5;
• —NQ6′SOCy3;
• —NQ6′—SO2Q5′;
• —NQ6′—SO2Ar5;
• —NQ6′—SO2Cy3;
• —OQ5′;
• —OAr5;
• —OCy3;
• —OCOQ5′;
• —OCOAr5;
• —OCOCy3;
• —COOQ5′;
• —COOAr5;
• —COOCy3;
• —OCOOQ5′;
• —OCOOAr5;
• —OCOOCy3;
• —CON(Q6′)Q5′;
• —CON(Q6′)Ar5;
• —CON(Q6′)Cy3;
• —CON(Q6′)OQ5′;
• —CON(Q6′)OAr5;
• —CON(Q6′)OCy3;
• —COQ5′;
• —COAr5;
• —COCy3;
• —SQ5′;
• —SAr5;
• —SCy3;
• —SOQ5′;
• —SOAr5;
• —SOCy3;
• —SO2Q5′;
• —SO2Ar5;
• —SO2Cy3;
• —SON(Q6′)Q5′;
• —SON(Q6′)Ar5;
• —SON(Q6′)Cy3;
• —SO2N(Q6′)Q5′;
• —SO2N(Q6′)Ar5;
• —SO2N(Q6′)Cy3;
• —SO3H;
• —NO2;
• and —CN;
• wherein
• Q5′, Q6′, Q7′, and Q8′ are independently hydrogen, alkyl, alkenyl or alkynyl;
• Ar5, Ar6, Cy3, and Cy4 are the same as defined above.