Furoisoquinoline derivatives, process for producing the same and use thereof

• US 6,924,292 B2
• Filed: 03/22/2001
• Issued: 08/02/2005
• Est. Priority Date: 03/23/2000
• Status: Expired due to Fees

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Fujii, Nobuhiro, Kawano, Yasuhiko, Uchikawa, Osamu, Matsumoto, Tatsumi, Tarui, Naoki
• Primary Examiner(s): Aulakh, Charanjit S.
• Application Number:
  US10/239,439
• Publication Number:
  US 20040092582A1
• Time in Patent Office: 1,594 Days
• Field of Search: 514/291, 514/212, 514/253, 514/275, 546/89, 546/22, 540/524, 544/238, 544/331, 544/405
• US Class Current: 514/291
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C07K 5/06017 and aliphatic
• CPC Class Codes: C07K 5/06026 the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
• CPC Class Codes: C12N 9/16 acting on ester bonds (3.1)
• CPC Class Codes: C12P 17/188 Heterocyclic compound containing in the condensed system at least one hetero ring having nitrogen atoms and oxygen atoms as the only ring heteroatoms ergot-alcaloids C12P17/183
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A compound having a partial structure represented by Formula:
or a salt thereof has an excellent phosphodiesterase (PDE) IV-inhibiting effect, and is useful as a prophylactic or therapeutic agent against inflammatory diseases, for example, bronchial asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, autoimmune disease, diabetes and the like.

Claims

1. A compound of the Formula:

wherein R¹ is a hydrogen atom, optionally substituted hydrocarbon group, optionally substituted heterocyclic group or optionally substituted amino group,

each of R² and R³ is a hydrogen atom, optionally substituted hydrocarbon group or acyl group, and R² and R³ may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered ring,

R⁴ is a hydrogen atom, cyano group, optionally substituted hydrocarbon group, acyl group or optionally substituted hydroxy group,

R⁵ is (1) a hydrogen atom, (2) an optionally substituted hydrocarbon group, (3) an acyl group, (4) an optionally substituted heterocyclic group or (5) a halogen atom,

each of R⁶ and R⁷ is a hydrogen atom or optionally substituted hydrocarbon group, and R⁶ and R⁷ may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered ring,

each of R⁸ and R⁹ is a hydrogen atom or optionally substituted hydrocarbon group,

X is a bond, oxygen atom, optionally oxidized sulfur atom or optionally substituted nitrogen atom,

Y is an optionally substituted methylene group or carbonyl group,

and n is 0 to

     1);

or a salt or a prodrug thereof.

2. The compound according to claim 1, wherein each of R² and R³ is a hydrogen atom, optionally substituted hydrocarbon group or acyl group, R² and R³ may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered homocyclic or heterocyclic group, R⁴ is a hydrogen atom or optionally substituted hydrocarbon group, each of R⁶ and R⁷ is a hydrogen atom or optionally substituted hydrocarbon group, R⁶ and R⁷ may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered homocyclic group, Y is methylene group which may have a hydroxy group or carbonyl group.

3. The compound according to claim 1 wherein R¹ is any of the following (i) to (iii):

(i) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from the group (hereinafter referred to as Substituent Group A) consisting of (1) a halogen atom, (2) a C_1-3 alkylenedioxy group, (3) a nitro group, (4) a cyano group, (5) an optionally halogenated C_1-6 alkyl group, (6) an optionally halogenated C_2-6 alkenyl group, (7) an optionally halogenated C_2-6 alkynyl group, (8) a C_3-6 cycloalkyl group, (9) a C_6-14 aryl group, (10) an optionally halogenated C_1-6 alkoxy group, (11) an optionally halogenated C_1-6 alkylthio group, (12) a hydroxy group, (13) an amino group, (14) a mono-C_1-6 alkylamino group, (15) a mono-C_6-14 arylamino group, (16) a di-C_1-6 alkylamino group, (17) a di-C_6-14 arylamino group, (18) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_{1-6 4} alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfmyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, (19) an acylamino group selected from formylamino, C_1-6 alkyl-carboxamido, C_6-14 aryl-carboxamido, C_1-6 alkoxy-carboxamido, C_1-6 alkylsulfonylamino and C_6-14 arylsulfonylaxnino, (20) an acyloxy group selected from C_1-6 alkyl-carbonyloxy, C_6-14 aryl-carbonyloxy, C_1-6 alkoxy-carbonyloxy, mono-C_1-6 alkyl-carbamoyloxy, di-C_1-6 alkyl-carbamoyloxy, C_6-14 aryl-carbamoyloxy and nicotinoyloxy, (21) a 4- to 14-membered heterocyclic group having, in addition to carbon atoms, 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms, (22) a phosphono group, (23) a C_6-14 aryloxy group, (24) a di-C_1-6 alkoxy-phosphoryl group, (25) a C_6-14 arylthio group, (26) a hydrazino group, (27) an amino group, (28) an oxo group, (29) an ureido group, (30) a C_1-6 alkyl-ureido group, (31) a di-C_1-6-alkyl-ureido group, (32) an oxide group and (33) a group formed by binding 2 or 3 groups selected from (1) to (32) listed above,

(ii) a 5- to 14-membered heterocyclic group having, in addition to carbon atoms, 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iii) an amino group which may have 1 or 2 substituent(s) selected from the following (ia) to (iiia);

(ia) a hydrogen atom,

(iia) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iiia) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbanoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C 1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above;

each of R² and R³ is any of the following (i) to (iii);

(i) a hydrogen atom,

(ii) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C₃₄ cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkcyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iii) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-14 aralkyl-carbonyl, C_6-14 aryloxy carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_3-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfmo, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above;

R² and R³ may be taken together with the adjacent carbon atom to form a C_3-8 cycloalkane or 3- to 8-membered heterocyclic ring which may have 1 to 3 substituent(s) selected from a C_1-6 alkyl, C_6-14 aryl, C_7-16 aralkyl, amino, mono-C_1-6 alkylamino, mono-C_6-14 arylamino, di-C_1-6 alkylamino, di-C_6-14 arylamino and 4- to 10-membered aromatic heterocyclic group;

R⁴ is (i) a hydrogen atom, (ii) a cyano group, (iii) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iv) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above, or,

(v) a group represented by Formula;

—

OR⁴

(R^4′

is <

1>

a hydrogen atom, <

2>

a C_1-6 alkyl group, C_2-6 alkenyl group, C₂ alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above, or, <

3>

an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-14 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above);

R⁵ is any of the following (i) to (v);

(i) a hydrogen atom,

(ii) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iii) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iv) a 5-to 14-membered heterocyclic ring containing ito 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 5 substituent(s) selected from Substituent Group A described above,

(v) a halogen atom;

each of R⁶ and R⁷ is (i) a hydrogen atom, (ii) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

R⁶ and R⁷ may be taken together with the adjacent carbon atom to form a C_3-8 cycloalkane or 3- to 8-membered heterocyclic ring which may have 1 to 3 substituent(s) selected from C_1-6 alkyl, C_6-14 aryl, C_7-16 aralkyl, amino, mono-C_1-6 alkylamino, mono-C_6-14 arylamino, di-C_1-6 alkylamino, di-C_6-14 arylamino and 4- to 10-membered aromatic heterocyclic group;

each of R⁸ and R⁹ is (i) a hydrogen atom, (ii) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above;

X is (i) a bond, (ii) an oxygen atom, (iii) an optionally oxidized sulfur atom, (iv) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(v) a nitrogen atom having an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above, or,

(vi) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 5 substituent(s) selected from Substituent Group A described above;

Y is <

1>

a methylene group which may have substituent(s) selected from Substituent Group A described above or <

2>

a carbonyl group;

n is 0 or 1.

4. The compound according to claim 1, wherein R¹ is (1) an optionally substituted aromatic hydrocarbon group, (2) an optionally substituted heterocyclic group, (3) an optionally substituted alicyclic hydrocarbon group or (4) a group represented by Formula:

—

L—

R^1a wherein L is methylene, carbonyl or an optionally substituted nitrogen atom, R^1a is a hydrogen atom, optionally substituted aromatic group, optionally substituted hydroxy group or optionally substituted amino group.

5. The compound according to claim 4, wherein R¹ is any of the following (i) to (iv):

(i) a C_1-6 aryl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(ii) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 5 substituent(s) selected from Substituent Group A described above,

(iii) a C_3-6 cycloalkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iv) a group represented by Formula —

L—

R^1a wherein L is (a) a methylene, (b) a carbonyl or (c) a nitrogen atom which may be substituted by the following (ia) to (iiia);

(ia) a hydrogen atom,

(iia) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iiia) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C, alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C₆, alkoxysulfinyl, C_6-14 aryloxysulflnyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

R^1a is (i) a hydrogen atom,

(ii) <

1>

a C_6-14 aryl group or <

2>

a 5- to 14-membered aromatic heterocyclic group containing 1 to 4 heteroatom(s) selected from 1 or 2 kind(s) of nitrogen, sulfur and oxygen atoms in addition to carbon atoms, both of which may contain 1 to 5 substituent(s) selected from Substituent Group A described above,

(iii) a hydroxy group which may have C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iv) an amino group which may be substituted by the following (ia) to (iiia);

(ia) a hydrogen atom, (iia) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(iiia) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyithiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl.

6. The compound according to claim 1 wherein R¹ is a group represented by Formula:

(wherein R^1b is a hydrogen atom or an optionally substituted hydrocarbon group or optionally substituted heterocyclic group, Ring D is an optionally substituted aromatic hydrocarbon ring or optionally substituted heterocyclic group, E is a bond, methylene, oxygen atom, optionally oxidized sulfur atom, optionally substituted nitrogen atom or a group represented by Formula;

—

CS—

O—

, —

CO—

O, —

S—

CO, —

(CH₂)_k—

CO—

, —

NR^1C—

CO—

(CH₂)_m—

, —

NR^1C—

SO₂—

(CH₂)_m—

, —

SO₂—

NR^1C—

(CH₂)_m—

, —

O—

CS—

NR^1C—

(CH₂)_m—

, —

NR^1C—

CO—

NR^1C—

(CH₂)_m—

, —

NR^1C—

CO—

(CH₂)_m—

NR^1C—

wherein R^1C is a hydrogen atom, optionally substituted alkyl group or acyl group, k is 0 or 1, m is an integer of 0 to 3.

7. The compound according to claim 6 wherein R^1b is (i) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above, or,

(ii) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 5 substituent(s) selected from Substituent Group A described above;

Ring D is (i) a C_6-14 aryl ring which may have 1 to 5 substituent(s) selected from Substituent Group A described above or (ii) a 5- to 14-membered heterocyclic ring containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 5 substituent(s) selected from Substituent Group A described above;

E is any of the following (i) to (viii);

(i) a bond, (ii) methylene, (iii) an oxygen atom, (iv) an optionally oxidized sulfur atom, (v) a C_1-6 alkyl group, C_2-6 alkenyl group, C_2-6 alkynyl group, C_3-6 cycloalkyl group, C_3-6 cycloalkenyl group, C_6-14 aryl group or C_7-16 aralkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above,

(vi) a nitrogen atom having an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbamoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkylthiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbamoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl,

(vii) a nitrogen atom having a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 5 substituent(s) selected from Substituent Group A described above;

(viii) —

CS—

O, —

CO—

O—

,—

S—

CO—

, —

CH₂)_k—

CO—

, —

NR^1C—

CO—

(CH₂)_m—

, —

NR^1C—

SO₂—

(CH₂)_m—

, —

SO₂—

NR^1C—

(CH₂)_m—

, —

O—

CS—

NR^1C—

CH₂)_m—

, —

NR^1C—

CO—

NR^1C—

(CH₂)_m—

NR^1C—

or —

NR^1C—

CO—

(CH₂)_m—

NR^1C—

wherein R^1C is (ia) a hydrogen atom, (iia) a C_1-6 alkyl group which may have 1 to 5 substituent(s) selected from Substituent Group A described above, or,

(iiia) an acyl group selected from formyl, carboxy, carbamoyl, C_1-6 alkyl-carbonyl, C_3-6 cycloalkyl-carbonyl, C_1-6 alkoxy-carbonyl, C_6-14 aryl-carbonyl, C_7-16 aralkyl-carbonyl, C_6-14 aryloxy-carbonyl, C_7-16 aralkyloxy-carbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbonyl, mono-C_1-6 alkyl-carbamoyl, di-C_1-6 alkyl-carbarnoyl, C_6-14 aryl-carbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-carbamoyl, C_1-6 alkyl-thiocarbonyl, C_3-6 cycloalkyl-thiocarbonyl, C_1-6 alkoxy-thiocarbonyl, C_6-14 aryl-thiocarbonyl, C_7-16 aralkyl-thiocarbonyl, C_6-14 aryloxy-thiocarbonyl, C_7-16 aralkyloxy-thiocarbonyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbonyl, thiocarbamoyl, mono-C_1-6 alkyl-thiocarbamoyl, di-C_1-6 alkyl-thiocarbamoyl, C_6-14 aryl-thiocarbamoyl, (5- or 6-membered heterocycle having, in addition to carbon atoms, 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-thiocarbanoyl, mono-C_1-6 alkylsulfamoyl, di-C_1-6 alkylsulfamoyl, C_6-14 arylsulfamoyl, C_1-6 alkylsulfonyl, C_6-14 arylsulfonyl, C_1-6 alkylsulfinyl, C_6-14 arylsulfinyl, sulfino, sulfo, C_1-6 alkoxysulfinyl, C_6-14 aryloxysulfinyl, C_1-6 alkoxysulfonyl and C_6-14 aryloxysulfonyl, which may have 1 to 5 substituent(s) selected from Substituent Group A described above;

k is 0 or 1, m is an integer of 0 to

     3).

8. The compound according to claim 6 wherein R^1b is;

(1) a C_1-6 alkyl group [this C_1-6 alkyl group may have a substituent selected from a halogen atom, cyano, hydroxy, C_1-6 alkoxy-carbonyl, di-C_1-6 alkylamino, optionally halogenated C_1-6 alkyl-carbonyl-amino, carboxy, carbamoyl, C_1-6 alkyl-carbamoyl, C_1-6 alkyl-carbonyloxy, C_1-6 alkoxy-carbonyl-C_1-6 alkyl-carbamoyl, (5- to 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl-carbamoyl, C_1-6 alkylthio, C_1-6 alkylsulfinyl, C_1-6 alkylsulfonylamino, (5- to 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkylcarbamoyl, (5- to 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-amino, sulfamoyl-C_6-14 aryl, carboxy-C_6-14 aryl, C_1-6 alkoxy-carbonyl-C_6-14 aryl, carbamoyl-C_6-14 aryl, C_1-6 alkyl-carbamoyl-C_6-14 aryl which may have a hydroxy and (4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbamoyl-C_6-14 aryl],

(2) a C_3-6 cycloalkyl group,

(3) a C_6-14 aryl group [this C_6-14 aryl group may have a substituent selected from C_1-6 alkoxy, amino, carboxy, optionally halogenated C_1-6 alkyl-carbonylamino, C_1-6 alkoxy-carbonylamino, formylamino, ureido, C_1-6 alkylsulfonylamino, (C_1-6 alkyl)(C_1-6 alkylsulfonyl) amino, C_1-6 alkoxy-carbonyl-C_1-6 alkylamino, optionally C_1-6 alkyl-esterified phosphono-C_1-6 alkylamino, mono- or di-C_1-6 alkyl-carbamoyl and C_7-16 aralkyloxy-carbonylamino]or, (4) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this heterocyclic group may be substituted by 1 or 2 substituent(s) selected from a halogen atom, C_1-6 alkyl, carboxy-C_1-6 alkyl, C_1-6 alkyl-carbonyloxy-C_1-6 alkyl, C_1-6 alkoxy-carbonyl, C_1-6 alkoxy-carbonyl-C_1-6 alkyl, C_1-6 alkyl-carbamoyl-C_1-6 alkyl, carbamoyl, oxo and 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms];

Ring D is (i) a C_6-14 aryl ring or (ii) a 5- to 14-membered heterocyclic ring containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms;

E is (I) a bond, (ii) methylene, (iii) O, (iv) S, (v) SO, (vi) SO₂, (vii) —

NH—

, (viii) —

N(C_1-6 alkyl)-, (ix) —

N(C_1-6 alkyl-carbonyl)-, (x) —

N(C_1-6 alkoxy-carbonyl)-, (xi) —

N(C_1-6 alkyl-sulfonyl)-, (xii)—

CO—

O—

, (xiii) —

S—

CO—

, (xiv) a group represented by Formula;

—

(CH₂)_k—

CO wherein k is 0 or 1, (xv) —

NR^f—

CO—

(CH₂)_m1—

wherein R^f is a hydrogen atom or C_1-6 alkoxy-carbonyl or C_1-6 alkyl group which may be substituted by a heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, oxygen, sulfur atoms and the like in addition to carbon atoms, and ml is an integer of 0 to 3,

(xvi) a group represented by Formula —

NR^g—

SO₂—

(CH₂)_m2—

wherein R^g is a hydrogen atom or C_1-6 alkyl-sulfonyl group and m2 is 0,

(xvii) a group represented by Formula —

SO₂—

NR^h—

(CH₂)_m3—

wherein R^h is a hydrogen atom or C_1-6 alkyl group and m3 is 0 or 1,

(xviii) a group represented by Formula —

O—

CS—

NRⁱ—

(CH₂)_m4—

wherein Rⁱ is a hydrogen atom or C_1-6 alkyl group and m4 is 0 or 1,

(xix) a group represented by Formula —

NR^j—

CO—

NR^k—

(CH₂)_m5—

wherein R^j is a hydrogen atom or C_1-6 alkyl group, R^k is a hydrogen atom or C_1-6 alkyl group and m5 is 0 or 1,

(xx) a group represented by Formula —

NR^L—

CO—

CH₂—

(CH₂)_m6—

—

NR^m—

wherein R^L is a hydrogen atom or C_1-6 alkyl group, R^m is a hydrogen atom or C_1-6 alkyl group and m6 is 0 or 1.

9. The compound according to claim 1 wherein R¹ is a group represented by Formula

wherein Hal is a halogen atom and Ring D is an optionally substituted aromatic hydrocarbon ring or optionally substituted heterocyclic group.

10. The compound according to claim 1, wherein R¹ is a group represented by Formula:

wherein R^1b is a hydrogen atom or an optionally substituted hydrocarbon group or optionally substituted heterocyclic group, Ring D is an optionally substituted aromatic hydrocarbon ring or optionally substituted heterocyclic group, E is a bond, methylene, oxygen atom, optionally oxidized sulfur atom, optionally substituted nitrogen atom or a group represented by Formula;

—

CS—

O—

, —

CO—

O—

, —

S—

CO—

, —

(CH₂)_k—

CO—

, —

NR^1C—

CO—

(CH₂)_m—

, —

NR^1C—

SO₂—

(CH₂)_m—

, —

SO₂—

NR^1C—

(CH₂)_m—

, —

O—

CS—

NR^1C—

(CH₂)_m—

, —

NR^1C—

CO—

NR^1C—

(CH₂)_m—

, —

NR^1C—

CO—

(CH₂)_m—

NR^1C—

wherein R^1C is a hydrogen atom, optionally substituted alkyl group or acyl group, k is 0 or 1, m is an integer of 0 to 3 or a group represented by Formula;

wherein Hal is a halogen atom each of R² and R³ is a hydrogen atom or optionally substituted hydrocarbon group, and R² and R³ may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered ring, R⁴ is a hydrogen atom, cyano group, optionally substituted hydrocarbon group, acyl group or a group represented by Formula;

—

OR^4′

wherein R^4′

a hydrogen atom, optionally substituted hydrocarbon group or acyl group, R⁵ is an optionally substituted hydrocarbon group, each of R⁶ and R⁷ is an optionally substituted hydrocarbon group, R⁶ and R⁷ may be taken together with the adjacent carbon atom to form an optionally substituted 3- to 8-membered ring, each of R⁸ and R⁹ is a hydrogen atom, X is an oxygen atom or an optionally oxidized sulfur atom, Y is methylene which may have 1 or 2 C_1-6 alkyl group(s) and n is 0 or 1.

11. The compound according to claim 1 wherein R¹ is, (i) a C_6-14 aryl group which may have 1 to 3 substituent(s) selected from the following (1) to (23):

(1) a halogen atom,

(2) a nitro group,

(3)a C_1-6alkyl group [this C_1-6 alkyl group may have a substituent selected from a halogen atom, cyano, carbamoyl, C_1-6 alkyl-carbamoyl, C_1-6 alkyl-carbonyloxy, C_1-6 alkoxy-carbonyl-C_1-6 alkyl-carbamoyl, (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl-carbamoyl, C_1-6 alkylsulfonylamino, C_1-6 alkoxy-carbonyl and carboxy],

(4) a C_3-6 cycloalkyl group,

(5) a C_6-14 aryl group [this C_6-14 aryl group may have a substituent selected from amino, carboxy, C_1-6 alkoxy-carbonyl, carbamoyl, mono- or di-C_1-6 alkylcarbamoyl, formylamino, C_1-6 alkyl-carbonylamino which may have a halogen atom or carboxy, C_6-14 aryl-carbonylamino, C_1-6 alkoxy-carbonylammo, ureido, mono- or di-C_1-6 alkylureido, C_1-6 alkylsulfonylamino, (C_1-6 allcyl)(C_1-6 alkylsulfonyl) amino, (C_1-6alkyl)(C_1-6 alkyl-carbonyl) amino, C_1-6 alkoxy-carbonyl-C_1-6 alkylamino, C_6-14 aralkyloxy-carbonylamino, C_1-6 alkyl-carbonylamino-C_1-6 alkyl-carbonylamino, C_1-6 allcylthio-C_1-6 alkyl-carbonylamino, C_1-6 alkyl-sulfinyl-C_1-6 alkyl-carbonylamino, C_1-6 alkyl-sulfonyl-C_1-6 alkyl-carbonylamino, C_6-14 aryloxy-carbonylamino and hydroxy-C_1-6 alkyl-carbamoyl],

(6) a C_1-6 alkoxy group which may have a halogen atom or C_1-6 alkoxy-C_6-14 aryl,

(7) a C_6-14 aryloxy group,

(8) a C_1-6 alkylthio group which may have a carbamoyl,

(9) a C_1-6 alkylsulfinyl group which may have a carbamoyl,

(10) a C_6-14 arylthio group,

(11) a hydroxy group,

(12) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms [this heterocyclic group may have a substituent selected from oxo, carboxy-C_1-6 alkyl, C_1-6 alkyl-carbonyloxy-C_1-6 alkyl, C_1-6 alkyl, C_1-6 alkoxy-carbonyl-C_1-6 alkyl, C,6 alkoxy-carbonyl, carbamoyl-C_1-6 alkyl and C_1-6 allcyl-carbamoyl-C_1-6 alkyl],

(13) a carboxy group,

(14) a group represented by Formula;

—

CO—

Hal (wherein Hal is a halogen atom),

(15) a C_1-6 alkyl-carbonyl group,

(16) a C_1-6 alkyl-sulfonyl group,

(17) a C_1-6 alkoxy-carbonyl group,

(18) a sulfamoyl group [this sulfamoyl group may have 1 or 2 substituent(s) selected from C_1-6 alkyl, carbamoyl-C_1-6 alkyl, C_1-6 alkoxy-carbonyl-C_1-6 alkyl, (5- to 8-membered heterocyclic ring which may have an oxo group)-C_1-6 alkyl and C_1-6 alkyl-carbonylamino-C_6-14 aryl],

(19) a group represented by Formula;

—

NR^aR^b [each of R^a and R^b is (i) a hydrogen atom, (ii) a C_1-6 alkyl, (iii) (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl, (iv) a C_1-6 alkoxy-carbonyl-C_1-6 alkyl, (v) a di-C_1-6 alkylamino-methylene-sulfamoyl-C_1-6 alkyl, (vi) a carbamoyl-C_1-6 alkyl, (vii) a sulfamoyl-C_1-6 alkyl, (viii) a C_1-6 alkyl-sulfonyl, (ix) a C_1-6 alkoxy-carbonyl, (x) a di-C_1-6 alkoxy-carbonyl-C_2-6 alkenyl, (xi) a C_6-14 aryl, (xii) a 5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this 5- or 6-membered heterocyclic group may have a substituent selected from amino, C_1-6 alkyl-carboxamido and C_1-6 alkyl-sulfonylamino], (xiii) an optionally halogenated-C_1-6 alkyl-carbonyl, (xiv) a C_1-6 alkylthio-C_1-6 alkyl-carbonyl, (xv) a C_{1-6 4} alkylsulfinyl-C_1-6 alkyl-carbonyl, (xvi) a C_1-6 alkylsulfonyl-C_1-6 alkyl-carbonyl, (xvii) an amino-C_1-6 alkyl-carbonyl, (xviii) an optionally halogenated C_1-6 alkyl-carbonyl-amino-C_1-6 alkyl-carbonyl, (xix) a C_1-6 aryl-carbonyl, (xx) a carboxy-C_6-14 aryl-carbonyl, (xxi) an optionally C_1-6 alkyl-esterified phosphono-C_1-6 alkyl-C_{1-6 14} aryl-carbonyl, (xxii) (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have a halogen atom, oxy or a C_1-6 alkoxy-carbonyl)-carbonyl, (xxiii) (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl-carbonyl, (xxiv) a C_6-14 aryl-oxy-carbonyl, (xxv) a carboxy-C_1-6 alkyl, (xxvi) a carbamoyl, (xxvii) an optionally halogenated C_1-6 alkylcarbamoyl, (xxviii) a C_6-14 arylcarbamoyl which may have a C_1-6 alkyl-carbonylamino, (xxix) (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbamoyl, (xxx) a C_2-6 alkenyl-carbonyl, (xxxi) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have an oxo group)-amino-C_1-6 alkyl-carbonyl, (xxxii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have an oxo group)(C_1-6 alkyl) amino-C_1-6 alkyl-carbonyl, (xxxiii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have an oxo group)(C_1-6 alkylcarbonyl) amino-C_1-6 alkyl-carbonyl, (xxxiv) a C_1-6 alkylthio-C_1-6 alkylcarbonyl (sulfur atom may be oxidized), (xxxv) an optionally halogenated C_1-6 alkylsulfonyl, (xxxvi) a sulfamoyl or (xxxvii) a C_1-6 alkylsulfamoyl],

(20) a group represented by Formula;

—

C(═

O)NR^cR^d [each of R^c and R^d is (i) a hydrogen atom, (ii) a C_1-6 alkyl, (iii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl, (iv) a carboxy-C₁₄₅alkyl, (v) a C_1-6 alkoxy-carbonyl-C_1-6 alkyl, (vi) a di-C_1-6 alkylamino-C_1-6 alkyl, (vii) a carbamoyl-C_1-6 alkyl, (viii) a C_1-6 alkylcaxbamoyl-C_1-6 alkyl, (ix) (5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkylcarbamoyl-C_1-6 alkyl, (x) (5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-amino-C_1-6 alkyl, (xi) a sulfamoyl-C_6-14 aryl-C_1-6 alkyl, (xii) a C_6-14 aryl which may have a C_1-6 alkoxy, (xiii) an optionally C_1-6 alkyl-esterified phosphono-C_1-6 alkyl-C_6-14 aryl, (xiv) a 4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this 4- to 10-membered heterocyclic group may have 1 to 2 substituent(s) selected from a halogen atom, C_1-6 alkyl and oxo], (xv) a C_6-14 aryl-carbamoyl-C_1-6 alkyl, (xvi) a hydroxy-C_1-6 alkyl or (xvii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have a oxo group)-carbamoyl-C_1-6 alkyl],

(21) a cyano group,

(22) a mono- or di-C_1-6 alkylcarbamoylthio group,

(23) a mono- or di-C_1-6 alkyithiocarbamoyloxy group;

(ii) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 3 substituent(s) selected from the following (1) to (8);

(1) a halogen atom,

(2) a C_1-6 alkyl group [this alkyl may have a substituent selected from carboxy, C_1-6 alkoxy, C_1-6 alkoxy-carbonyl, mono-C_1-6 alkyl-amino, di-C_1-6 alkyl-amino, carbamoyl, C_1-6 alkyl-carbamoyl which may have a hydroxy, 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have oxo, (4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbamoyl, carbamoyl-C_1-6 alkyl-carbamoyl],

(3) a C_1-6 alkoxy group,

(4) a C_6-14 aryl group,

(5) a C_7-16 aralkyl group [this C_7-16 aralkyl group may have a substituent selected from carboxy, C_1-6 alkoxy-carbonyl, carbamoyl, C_1-6 alkyl-carbamoyl which may have a hydroxy, (4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbamoyl],

(6) a 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this 4- to 10-membered heterocyclic group may have a substituent selected from a C_1-6 alkyl, C_1-6 alkoxy-carbonyl, carbamoyl, oxo, 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms],

(7) an oxo group,

(8) an oxide group;

(iii) a C_3-6 cycloalkyl group;

or,

(iv) a group represented by Formula;

—

L′

—

R^1a (L′

is methylene, carbonyl or an optionally substituted nitrogen atom, R^1a′

is (1) a hydrogen atom, (2) a C_6-14 aryl group which may have 1 to 5 substituent(s) selected from a C_1-6 alkyl and C_1-6 alkoxy, (3) a hydroxy group which may be substituted by a C_1-6 alkyl group, (4) a C_1-6 alkyl-amino group which may be substituted by a 4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms in addition to carbon atoms, (6) a C_6-14 aryl-amino group or (7) a (4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms in addition to carbon atoms)-amino group),

each of R² and R³ is (1) a hydrogen atom, (2) a C_1-6 alkyl group which may be substituted by <

1>

a halogen atom, <

2>

a hydroxy group which may be substituted by a substituent selected from a C_1-6 alkyl, C_1-6 alkyl-carbonyl, C_1-6 alkylsulfonyl and C_7-16 aralkyl, <

3>

an amino group which may be substituted by 1 or 2 C_1-6 alkyl, C_3-6 alkyl-carbonyl and C_6-14 aryl-carbonyl, <

4>

a 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms in addition to carbon atoms, <

5>

a thio group which may be substituted by C_1-6 alkyl, <

6>

a C_1-6 alkyl-sulfinyl group or <

7>

a C_1-6 alkyl-sulfonyl group, or (3) a C_1-6 alkoxy-carbonyl group,

R² and R³ may be taken together with the adjacent carbon atom to form a C_3-8 cycloalkane,

R⁴ is (i) a hydrogen atom, (ii) a cyano group, (iii) a C_1-6 alkyl group [this C_1-6 alkyl group may have a substituent selected from (1) a halogen atom, (2) a cyano group, (3) a C_1-6 alkoxy group, (4) a hydroxy group, (5) an amino group, (6) a mono-C_1-6 alkylamino group, (7) a di-C_1-6 alkylamino group, (8) a tri-C_1-6 alkylammonium group, (8) a 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have an oxo, (9) a C_6-14 arylthio, (10) an ureido, (11) a carboxy, (12) a carbamoyl, (13) a C_1-6 alkoxy-carbonyl, (14) a mono-C_1-6 alkyl-carbamoyl, (15) a formylamino and (16) a C_1-6 alkyl-carboxamide],

(iv) a C_2-6 alkenyl group or (v) a formyl group;

X is a bond, oxygen atom, optionally oxidized sulfur atom, —

NH—

or —

N(methyl)-,

R⁵ is,

when X is a bond, then (i) a hydrogen atom, (ii) a C_1-6 alkyl group or (iii) a halogen atom,

when X is an oxygen atom, then (i) a hydrogen atom, (ii) a C_1-6 alkyl group [this C_1-6 alkyl group may have a substituent selected from (1) a halogen atom, (2) a hydroxy group, (3) an amino group, (4) a carboxy, (5) a carbamoyl, (6) a C_1-6 alkoxy-carbonyl, (7) a mono-C_1-6 alkyl-carbamoyl, (8) a di-C_1-6 alkyl-carbamoyl, (9) a 4- to 10-membered heterocydic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms], (iii) a C_2-6 alkenyl group [this C_2-6 alkenyl group may have a C_1-6 aryl], (iv) a C_2-6 alkynyl group, (v) a C_3-6 cycloalkyl group, (vi) a C_7-16 aralkyl group, (vii) a C_1-6 alkyl-carbonyl group, (viii) a C_6-14 aryl-carbonyl group, (ix) a C_1-6 alkoxy-carbonyl group, (x) a mono- or di-C_1-6 alkyl-thiocarbamoyl group, (xi) an optionally halogenated C_1-6 alkyl-sulfonyl group or (xii) a 4- to 10-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this beterocyclic group may have a C_6-14 aryl],

when X is an optionally oxidized sulfur, then (i) a C_1-6 alkyl group or (ii) a mono- or di-C_1-6 alkyl-carbamoyl group,

when X is —

NH—

or —

N(methyl)-, then (i) a hydrogen atom, (ii) a C_1-6 alkyl group [this C_1-6 alkyl group may have a C_1-6 alkoxy-carbonyl], (iii) formyl, (iv) a C_1-6 alkyl-carbonyl group, (v) a C_1-6 alkoxy-carbonyl group, (vi) a carbamoyl group, (vii) a mono- or di-C_1-6 alkyl-carbamoyl group or (viii) a C_1-6 alkyl-sulfonyl group,

each of R⁶ and R⁷ is a hydrogen atom or C_1-6 alkyl group,

R⁶ and R⁷ may be taken together with the adjacent carbon atom to form a C_3-8 cycloalkane,

Each of R⁸ and R⁹ is a hydrogen atom or a C_1-6 alkyl group,

Y is <

1>

a methylene group which may have 1 or 2 C_1-6 alkyl or hydroxy group or <

2>

a carbonyl group,

n is 0 or 1.

12. The compound according to claim 2, wherein R¹ is, (i) a C_6-14 aryl group which may have 1 to 3 substituent(s) selected from the following (1) to (20):

(1) a halogen atom,

(2) a nitro group,

(3) a C_1-6 alkyl group [this C_1-6 alkyl group may have a substituent selected from a halogen atom, cyano, carbamoyl, C_1-6 alkyl-carbamoyl, C_1-6 alkyl-carbonyloxy, C_1-6 alkoxy-carbonyl-C_1-6 alkyl-carbamoyl, (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl-carbamoyl, C_1-6 alkylsulfonylamino, C_1-6 alkoxy-carbonyl and carboxy],

(4) a C_3-6 cycloalkyl group,

(5) a C_6-14 aryl group [this 06-14 aryl group may have a substituent selected from amino, optionally halogenated C_1-6 alkyl-carbonylamino, ureido, C_1-6 alkylsulfonylamino, (C_1-6 alkyl)(C_1-6 alkylsulfonyl) amino, C_1-6 alkoxy-carbonyl-C_1-6 alkylamino],

(6) a C_1-6 alkoxy group which may have a halogen atom or C_1-6 alkoxy-C_6-14 aryl,

(7) a C_6-14 aryloxy group,

(8) a C_1-6 alkylthio group,

(9) a C_1-6 alkylsulfinyl group,

(10) a C_6-14 arylthio group,

(11) a hydroxy group,

(12) a 5- to 1 4-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms [this heterocyclic group may have a substituent selected from oxo, carboxy-C_1-6 alkyl, C_1-6 alkyl-carbonyloxy-C_1-6 alkyl, C_1-6 alkoxy-carbonyl-C_1-6 alkyl, C_1-6 alkyl-carbamoyl-C_1-6 alkyl],

(13) a carboxy group,

(14) a group represented by Formula;

—

CO—

Hal (Hal is a halogen atom),

(15) a C_1-6 alkyl-carbonyl group,

(16) a C_1-6 alkyl-sulfonyl group,

(17) a C_1-6 alkoxy-carbonyl group,

(18) a sulfamoyl group [this sulfamoyl group may have a substituent selected from C_1-6 alkyl, carbamoyl-C_1-6 alkyl, (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl],

(19) a group represented by Formula;

—

NR^aR^b [each of R^a and R^b is (i) a hydrogen atom, (ii) a C_1-6 alkyl, (iii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl, (iv) a C_1-6 alkoxy-carbonyl-C_1-6 alkyl, (v) a di-C_1-6 alkylamino-methylene-sulfamoyl-C_2-6 alkyl, (vi) a carbamoyl-C_1-6 alkyl, (vii) a sulfamoyl-C_1-6 alkyl, (viii) a C_1-6 alkyl-sulfonyl, (ix) a C_1-6 alkoxy-carbonyl, (x) a di-C_1-6 alkoxy-carbonyl-C_1-6 alkenyl, (xi) a C₆₁₄ aryl, (xii) a 5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this 5- or 6-membered heterocyclic group may have a substituent selected from amino, C_1-6 alkyl-carboxamido and C_1-6 alkyl-sulfonylamino], (xiii) an optionally halogenated C_1-6 alkyl-carbonyl, (xiv) a C_1-6 alkylthio-C_1-6 alkyl-carbonyl, (xv) a C_1-6 alkylsulfinyl-C_1-6 alkyl-carbonyl, (xvi) a C_1-6 alkylsulfonyl-C_1-6 alkyl-carbonyl, (xvii) an amino-C_1-6 alkyl-carbonyl, (xviii) an optionally halogenated C_1-6 alkyl-carbonyl-amino-C_1-6 alkyl-carbonyl, (xix) a C_6-14 aryl-carbonyl, (xx) a carboxy-C_6-14 aryl-carbonyl, (xxi) an optionally C_1-6 alkyl-esterified phosphono-C_1-6 alkyl-C_6-14 aryl-carbonyl, (xxii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbonyl, (xxiii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have a C_1-6 alkoxy-carbonyl)-C_1-6 alkyl-carbonyl, (xxiv) a C_6-14 aryl-oxy-carbonyl, (xxv) a carboxy-C_1-6 alkyl or (xxvi) a carbamoyl],

(20) a group represented by Formula;

—

C(═

O)NR^cR^d [each of R^c and R^d is (i) a hydrogen atom, (ii) a C_1-6 alkyl, (iii) a (5- or 6-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-C_1-6 alkyl, (iv) a carboxy-C_1-6 alkyl, (v) a C_1-6 alkoxy-carbonyl-C_1-6 alkyl, (vi) a di-C_1-6 alkylamino-C_1-6 alkyl, (vii) a carbamoyl-C_1-6 alkyl, (viii) a C_1-6 alkylcarbamoyl-C_1-6 alkyl, (ix) a (5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-C_1-6 alkyl carbamoyl-C_1-6 alkyl, (x) a (5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-amino-C_1-6 alkyl, (xi) a sulfamoyl-C_6-14 aryl-C_1-6 alkyl, (xii) a C_6-14 aryl which may have a C_1-6 alkoxy, (xiii) a C_1-6 alkyl-C_1-14 aryl which have an optionally C_1-6 alkyl-esterified phosphono group, (xiv) a 4- to 10-membered heterocyclic ring containing to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this heterocyclic group may have 1 or 2 substituent(s) selected from a halogen atom, C_1-6 alkyl and oxo] or (xv) a C_6-14 aryl-carbamoyl-C_1-6 alkyl;

(ii) a 5- to 14-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may contain 1 to 3 substituent(s) selected from the following (1) to (8);

(1) a halogen atom,

(2) a C_1-6 alkyl group [this alkyl may have a substituent selected from carboxy, C_1-6 alkoxy, C_1-6 alkoxy-carbonyl, mono-C_1-6 alkyl-amino, di-C_1-6 alkyl-amino, carbamoyl, C_1-6 alkyl-carbamoyl which may have a hydroxy, 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have oxo, (4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbamoyl, carbamoyl-C_1-6 alkyl-carbamoyl],

(3) a C_1-6 alkoxy group,

(4) a C_6-14 aryl group,

(5) a C_7-16 aralkyl group [this C_7-16 aralkyl group may have a substituent selected from carboxy, C_1-6 alkoxy-carbonyl, carbamoyl, C_1-6 alkyl-carbamoyl which may have a hydroxy, (4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms)-carbamoyl], (6) a 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this 4- to 10-membered heterocyclic group may have a substituent selected from a C_1-6 alkyl, C_1-6 alkoxy-carbonyl, carbamoyl, oxo, 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms],

(7) an oxo group,

(8) an oxide group;

(iii) a C_3-6 cycloalkyl group;

or,

(iv) a group represented by Formula;

—

L′

—

R^1a (L′

is methylene, carbonyl or —

NH—

, R^1a is (1) a hydrogen atom, (2) a C_6-14 aryl group which may have 1 to 5 substituent(s) selected from a C_1-6 alkyl and C_1-6 alkoxy, (3) a hydroxy group which may be substituted by a C_1-6 alkyl group, (4) a C_1-6 alkyl-amino group which may be substituted by a 4- to 10-membered heterocyclic ring containing 1 to 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms in addition to carbon atoms, (6) a C_6-14 aryl-amino group or (7) a (4- to 10-membered heterocyclic ring containing 1 to3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms in addition to carbon atoms)-amino group),

each of R² and R³ is (1) a hydrogen atom, (2) an optionally halogenated C_1-6 alkyl group or (3) a C_1-6 alkoxy-carbonyl group,

R² and R³ may be taken together with the adjacent carbon atom to form a C_3-8 cycloalkane,

R⁴ is (i) a hydrogen atom, (ii) a C_1-6 alkyl group [this C_1-6 alkyl group may have a substituent selected from (1) a halogen atom, (2) a cyano group, (3) a C_1-6 alkoxy group, (4) a hydroxy group, (5) an amino group, (6) a mono-C_1-6 alkylamino group, (7) a di-C_1-6 alkylamino group, (8) a tri-C_1-6 alkylammonium group, (9) a 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have an oxo, (10) a C_6-14 arylthio, (11) an ureido, (12) a carboxy, (13) a carbamoyl, (14) a C_1-6 alkoxy-carbonyl, (15) a mono-C_1-6 alkyl-carbamoyl, (16) a formylamino, (17) a C_1-6 alkyl-carboxamido] or (iii) a C_2-6 alkenyl group;

X is a bond, oxygen atom, sulfur atom, —

NH—

or —

N(methyl)-,

R⁵ is,

when X is a bond, then (i) a hydrogen atom, (ii) a C_1-6 alkyl group or (iii) a halogen atom,

when X is an oxygen atom, then (i) a hydrogen atom, (ii) a C_1-6 alkyl group [this C_1-6 alkyl group may have a substituent selected from (1) a halogen atom, (2) a hydroxy group, (3) an amino group, (4) a carboxy, (5) a carbamoyl, (6) a C_1-6 alkoxy-carbonyl, (7) a mono-C_1-6 alkyl-carbamoyl, (8) a di-C_1-6 alkyl-carbamoyl, (9) a 4- to 10-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms which may have an oxo], (iii) a C_2-6 alkenyl group [this C_2-6 alkenyl group may have a C_6-14 aryl], (iv) a C_2-6 alkynyl group, (v) a C_3-6 cycloalkyl group, (vi) a C_7-16 aralkyl group, (vii) a C_1-6 alkyl-carbonyl group, (viii) a C_6-14 aryl-carbonyl group, (ix) a C_1-6 alkoxy-carbonyl group, (x) a mono- or di-C_1-6 alkyl-thiocarbamoyl group, (xi) an optionally halogenated C_1-6 alkyl-sulfonyl group or (xii) a 4- to 10-membered heterocyclic group containing 1 to 4 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms in addition to carbon atoms [this heterocyclic group may have a C_6-14 aryl],

when X is a sulfur, then (i) a C_1-6 alkyl group or (ii) a mono- or di-C_1-6 alkyl-carbamoyl group,

when X is —

NH—

or —

N(methyl)-, then (i) a hydrogen atom, (ii) a C_1-6 alkyl group [this C_1-6 alkyl group may have a C_1-6 alkoxy-carbonyl], (iii) formyl, (iv) a C_1-6 alkyl-carbonyl group, (v) a C_1-6 alkoxy-carbonyl group, (vi) a carbamoyl group, (vii) a mono- or di-C_1-6 alkyl-carbamoyl group or (viii) a C_1-6 alkyl-sulfonyl group,

each of R⁶ and R⁷ is a hydrogen atom or C_1-6 alkyl group,

R⁶ and R⁷ may be taken together with the adjacent carbon atom to form a C_3-8 cycloalkane,

each of R⁸ and R⁹ is a hydrogen atom or a C_1-6 alkyl group,

Y is a methylene group which may have a hydroxy group or carbonyl group,

n is 0 or 1.

13. The compound according to claim 1, wherein each of R² and R³ is a C_1-6 alkyl group.

14. The compound according to claim 1, wherein R⁴ is a hydrogen atom.

15. The compound according to claim 1, wherein each of R⁶ and R⁷ is a C_1-6 alkyl group.

16. The compound according to claim 1, wherein each of R⁸ and R⁹ is a hydrogen atom.

17. The compound according to claim 1, wherein n is 0.

19. A prodrug of a compound according to claim 1.

20. A process for producing a compound according to claim 1, comprising:

reacting a compound represented by Formula;

wherein each symbol is defined as described in claim 2 or a salt thereof with a compound represented by Formula;

R¹ —

CN or Formula;

R¹ —

CONH₂ wherein R¹ is defined as described in claim 2 or a salt thereof, or,

reacting a compound represented by Formula;

wherein Z is an optionally substituted hydroxy group or halogen atom, and other symbols are defined as described in claim 2 or a salt thereof with a compound represented by Formula;

R¹ —

CN wherein R¹ is defined as described in claim 2 or a salt thereof.

21. A pharmaceutical composition comprising a compound according to claim 1 or a salt or prodrug thereof and a pharmaceutically acceptable carrier, excipient or diluent.

22. A pharmaceutical composition comprising (1) a compound according to claim 1 or a salt or prodrug thereof in combination with (2) a drug selected from antiasthma agents, antiallergic agents, anticholinergic agents, antiinflammatory agents, antibacterial agents, antifungal agents and antidiabetic agents.

23. A method for inhibiting a phosphodiesterase IV comprising administering an effective amount of the compound according to claim 1 or a salt or prodrug thereof to a mammal.

24. A method for treating inflammatory diseases comprising administering an effective amount of the compound according to claim 1 or a salt or prodrug thereof to a mammal.

25. A method for treating asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, autoimmune disease or diabetes comprising administering an effective amount of the compound according to claim 1 or a salt or prodrug thereof to a mammal.

26. A method for treating inflammatory diseases comprising administering (1) an effective amount of the compound according to claim 1 or a salt or prodrug thereof in combination with (2) an effective amount of a drug selected from antiasthma agents, antiallergic agents, anticholinergic agents, antiinflammatory agents, antibacterial agents, antifungal agents and antidiabetic agents to a mammal.

27. A method for treating asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, autoinimune disease or diabetes comprising administering (1) an effective amount of the compound according to claim 1 or a salt or prodrug thereof in combination with (2) an effective amount of a drug selected from antiasthma agents, antiallergic agents, anticholinergic agents, antiinflammatory agents, antibacterial agents, antifungal agents and antidiabetic agents to a mammal.

18. (i) 2-(methylsulfinyl)—

N—

[3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)phenyl]acetamide, (ii) N-(methylsulfonyl)-N-[3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)phenyl]methanesulfonamide, (iii) N-[2-(4-pyridinyl)ethyl]-3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro [2,3-h]isoquinolin-1-yl)benzamide, (iv) N-(2-amino-2-oxoethyl)-3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide, (v)N-methyl-3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide, (vi) N-ethyl-3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide, (vii) N-[3′

-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)[1,1′

-biphenyl]-3-yl]acetamide, (viii) N-(2-amino-1,1-dimethyl-2-oxoethyl)-3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide, (ix)3-(6-ethoxy-3,4,8,9-tetrahydro-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)-N-methylbenzamide, (x) N-(2-amino-2-oxoethyl)-3-(6-ethoxy-3,4,8,9-tetrahydro-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide, (xi) N-(2-amino-1,1-dimethyl-2-oxoethyl)-3-(6-ethoxy-3,4,8,9-tetrahydro-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide, (xii)N-(3-(6-ethoxy-3 4,8,9-tetrahydro-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)phenyl]methanesulfonamide, (xiii) N-(hydroxymethyl)-3-(3,4,8,9-tetrahydro-6-methoxy-3,3,8,8-tetramethylfuro[2,3-h]isoquinolin-1-yl)benzamide or its salts.