Novel alkylene derivatives

A compound of Formula (I):

• or its pharmaceutically acceptable salt,
• wherein
• R1 is substituted or unsubstituted fused aromatic heterocyclyl, substituted or unsubstituted fused aromatic carbocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, the group represented by Formula:
• or substituted or unsubstituted 5-membered aromatic heterocyclyl,
• X1 is N or C(Rx1),
• X2 is N or C(Rx2),
• X3 is N or C(Rx3),
• X4 is N or COO,
• each Rx1, Rx2, Rx3, and Rx4 is independently hydrogen, halogen, hydroxy, carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl,
• Rx5 is halogen, hydroxy, carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl,
• ring A is substituted or unsubstituted non-aromatic carbocycle, substituted or unsubstituted non-aromatic heterocycle, substituted or unsubstituted aromatic carbocycle or substituted or unsubstituted aromatic heterocycle,
• -L1- is —O—(CR6R7)m- or —N(R8)—(CR6R7)m-,
• -L2- is —O—(CR6R7)n-, —O—CR6═CR7—, —(CR6R7)n- or —C(═O)—(CR6R7)n-,
• each R6 is independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl,
• each R7 is independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl, or R6 and R7 on the same carbon atom may be taken together with the carbon atom to form ring, or R2 is taken together with either R6 or R7 to form ring,
• each m is independently an integer of 0, 1, 2 or 3,
• each n is independently an integer of 1, 2 or 3,
• R2 is substituted or unsubstituted alkyl,
• R3 is hydrogen or substituted or unsubstituted alkyl,
• R4 is substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl;
• provided that the following compounds are excluded,
• (i) the compounds wherein R1 is a substituent selected from Substituent group α (Substituent group α:
• unsubstituted phenyl and substituted or unsubstituted aromatic heterocyclyl) and quinolinyl substituted with two alkyloxy groups, ring A is substituted pyrrolidine, and -L2- is —C(═O)—(CR6R7)n-,
• (ii) the compounds wherein ring A is nitrogen-containing non-aromatic heterocycle, -L2- is —C(═O)—(CR6R7)n-, and the atom on ring A bonded to -L2- is nitrogen,
• (iii) the compounds wherein R1 is benzimidazolyl substituted with substituted or unsubstituted aromatic heterocyclylalkyl or substituted or unsubstituted non-aromatic heterocyclylalkyl, ring A is piperidine, -L1- is —NH—, -L2- is —CH2—, and R4 is tert-butyloxycarbonyl,
• (iv) the compounds wherein R1 is substituted or unsubstituted fused aromatic heterocyclyl represented by Formula:
• wherein
• ring B is 5-membered, and ring C is 6-membered,
• and -L2- is —C(═O)—(CR6R7)n-,
• (v) the compounds wherein X1 is C(Rx1), X2 is C(Rx2), X3 is C(Rx3), X4 is C(Rx4), Rx5 is unsubstituted carbamoyl, ring A is unsubstituted cyclohexane, -L1- is —N(H)—, -L2- is —C(═O)—, and R4 is alkylcarbonyl substituted with amino or unsubstituted alkyloxycarbonyl,
• and
• (vi) the following compounds:
• (1-a) A compound of Formula (I):
• or its pharmaceutical acceptable salt,
• wherein
• R1 is substituted or unsubstituted fused aromatic heterocyclyl, substituted or unsubstituted fused aromatic carbocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, the group represented by Formula:
• or substituted or unsubstituted 5-membered aromatic heterocyclyl,
• X1 is N or C(Rx1),
• X2 is N or C(Rx2),
• X3 is N or C(Rx3),
• X4 is N or C(Rx4),
• each Rx1, Rx2, Rx3, and Rx4 is independently hydrogen, halogen, hydroxy, carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl,
• Rx5 is halogen, hydroxy, carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl,
• ring A is substituted or unsubstituted non-aromatic carbocycle, substituted or unsubstituted non-aromatic heterocycle, substituted or unsubstituted aromatic carbocycle or substituted or unsubstituted aromatic heterocycle,
• -L1- is —O—(CR6R7)m- or —N(R8)—(CR6R7)m-,
• -L2- is —O—(CR6R7)n-, —O—CR6═CR7—, —(CR6R7)n- or —C(═O)—(CR6R7)n-,
• each R6 is independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl,
• each R7 is independently hydrogen, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl, or R6 and R7 on the same carbon atom may be taken together with the carbon atom to form ring, or R2 is taken together with either R6 or R7 to form ring,
• each m is independently an integer of 0, 1, 2 or 3,
• each n is independently an integer of 1, 2 or 3,
• R2 is substituted or unsubstituted alkyl,
• R3 is hydrogen or substituted or unsubstituted alkyl,
• R4 is substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted sulfamoyl;
• provided that the following compounds are excluded,
• (i) the compounds wherein R1 is a substituent selected from Substituent group α (Substituent group α:
• unsubstituted phenyl and substituted or unsubstituted aromatic heterocyclyl) and quinolinyl substituted with two alkyloxy groups, ring A is substituted pyrrolidine, and -L2- is —C(═O)—(CR6R7)n-,
• (ii) the compounds wherein ring A is nitrogen-containing non-aromatic heterocycle, -L2- is —C(═O)—(CR6R7)n-, and the atom on ring A bonded to -L2- is nitrogen,
• (iii) the compounds wherein R1 is benzimidazolyl or imidazopyridyl substituted with substituted or unsubstituted aromatic heterocyclylalkyl or substituted or unsubstituted non-aromatic heterocyclylalkyl, ring A is piperidine, -L′- is —NH—, -L2- is —CH2—, and R4 is tert-butyloxycarbonyl,
• (iv) the compounds wherein R1 is substituted or substituted fused aromatic heterocyclyl represented by Formula:
• wherein
• ring B is 5-membered, and ring C is 6-membered,
• (iv) the compounds wherein X′ is C(Rx1), X2 is C(Rx2), X3 is C(Rx3), X4 is C(Rx4), Rx5 is unsubstituted carbamoyl, ring A is unsubstituted cyclohexane, -L1- is —N(H)—, -L2- is —C(═O)—, and R4 is alkylcarbonyl substituted with amino or unsubstituted alkyloxycarbonyl,
• and
• (v) the following compounds: