Furoisoquinoline derivatives, process for producing the same and use thereof
First Claim
Patent Images
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 Assignments
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Accused Products
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.
-
Citations
27 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.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27)
(wherein R1b 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—
, —
NR1C—
CO—
(CH2)m—
, —
NR1C—
SO2—
(CH2)m—
, —
SO2—
NR1C—
(CH2)m—
, —
O—
CS—
NR1C—
(CH2)m—
, —
NR1C—
CO—
NR1C—
(CH2)m—
, —
NR1C—
CO—
(CH2)m—
NR1C—
wherein R1C 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 R1b is (i) a C1-6 alkyl group, C2-6 alkenyl group, C2-6 alkynyl group, C3-6 cycloalkyl group, C3-6 cycloalkenyl group, C6-14 aryl group or C7-16 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 C6-14 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 C1-6 alkyl group, C2-6 alkenyl group, C2-6 alkynyl group, C3-6 cycloalkyl group, C3-6 cycloalkenyl group, C6-14 aryl group or C7-16 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, C1-6 alkyl-carbonyl, C3-6 cycloalkyl-carbonyl, C1-6 alkoxy-carbonyl, C6-14 aryl-carbonyl, C7-16 aralkyl-carbonyl, C6-14 aryloxy-carbonyl, C7-16 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-C1-6 alkyl-carbamoyl, di-C1-6 alkyl-carbamoyl, C6-14 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, C1-6 alkylthiocarbonyl, C3-6 cycloalkyl-thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C6-14 aryl-thiocarbonyl, C7-16 aralkyl-thiocarbonyl, C6-14 aryloxy-thiocarbonyl, C7-16 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-C1-6 alkyl-thiocarbamoyl, di-C1-6 alkyl-thiocarbamoyl, C6-14 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-C1-6 alkylsulfamoyl, di-C1-6 alkylsulfamoyl, C6-14 arylsulfamoyl, C1-6 alkylsulfonyl, C6-14 arylsulfonyl, C1-6 alkylsulfinyl, C6-14 arylsulfinyl, sulfino, sulfo, C1-6 alkoxysulfinyl, C6-14 aryloxysulfinyl, C1-6 alkoxysulfonyl and C6-14 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—
, —
NR1C—
CO—
(CH2)m—
, —
NR1C—
SO2—
(CH2)m—
, —
SO2—
NR1C—
(CH2)m—
, —
O—
CS—
NR1C—
CH2)m—
, —
NR1C—
CO—
NR1C—
(CH2)m—
NR1C—
or —
NR1C—
CO—
(CH2)m—
NR1C—
wherein R1C is (ia) a hydrogen atom, (iia) a C1-6 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, C1-6 alkyl-carbonyl, C3-6 cycloalkyl-carbonyl, C1-6 alkoxy-carbonyl, C6-14 aryl-carbonyl, C7-16 aralkyl-carbonyl, C6-14 aryloxy-carbonyl, C7-16 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-C1-6 alkyl-carbamoyl, di-C1-6 alkyl-carbarnoyl, C6-14 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, C1-6 alkyl-thiocarbonyl, C3-6 cycloalkyl-thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C6-14 aryl-thiocarbonyl, C7-16 aralkyl-thiocarbonyl, C6-14 aryloxy-thiocarbonyl, C7-16 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-C1-6 alkyl-thiocarbamoyl, di-C1-6 alkyl-thiocarbamoyl, C6-14 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-C1-6 alkylsulfamoyl, di-C1-6 alkylsulfamoyl, C6-14 arylsulfamoyl, C1-6 alkylsulfonyl, C6-14 arylsulfonyl, C1-6 alkylsulfinyl, C6-14 arylsulfinyl, sulfino, sulfo, C1-6 alkoxysulfinyl, C6-14 aryloxysulfinyl, C1-6 alkoxysulfonyl and C6-14 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 R1b is;
-
(1) a C1-6 alkyl group [this C1-6 alkyl group may have a substituent selected from a halogen atom, cyano, hydroxy, C1-6 alkoxy-carbonyl, di-C1-6 alkylamino, optionally halogenated C1-6 alkyl-carbonyl-amino, carboxy, carbamoyl, C1-6 alkyl-carbamoyl, C1-6 alkyl-carbonyloxy, C1-6 alkoxy-carbonyl-C1-6 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)-C1-6 alkyl-carbamoyl, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 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)-C1-6 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-C6-14 aryl, carboxy-C6-14 aryl, C1-6 alkoxy-carbonyl-C6-14 aryl, carbamoyl-C6-14 aryl, C1-6 alkyl-carbamoyl-C6-14 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-C6-14 aryl], (2) a C3-6 cycloalkyl group, (3) a C6-14 aryl group [this C6-14 aryl group may have a substituent selected from C1-6 alkoxy, amino, carboxy, optionally halogenated C1-6 alkyl-carbonylamino, C1-6 alkoxy-carbonylamino, formylamino, ureido, C1-6 alkylsulfonylamino, (C1-6 alkyl)(C1-6 alkylsulfonyl) amino, C1-6 alkoxy-carbonyl-C1-6 alkylamino, optionally C1-6 alkyl-esterified phosphono-C1-6 alkylamino, mono- or di-C1-6 alkyl-carbamoyl and C7-16 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, C1-6 alkyl, carboxy-C1-6 alkyl, C1-6 alkyl-carbonyloxy-C1-6 alkyl, C1-6 alkoxy-carbonyl, C1-6 alkoxy-carbonyl-C1-6 alkyl, C1-6 alkyl-carbamoyl-C1-6 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 C6-14 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(C1-6 alkyl)-, (ix) —
N(C1-6 alkyl-carbonyl)-, (x) —
N(C1-6 alkoxy-carbonyl)-, (xi) —
N(C1-6 alkyl-sulfonyl)-, (xii)—
CO—
O—
, (xiii) —
S—
CO—
, (xiv) a group represented by Formula;
—
(CH2)k—
CO wherein k is 0 or 1, (xv) —
NRf—
CO—
(CH2)m1—
wherein Rf is a hydrogen atom or C1-6 alkoxy-carbonyl or C1-6 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 —
NRg—
SO2—
(CH2)m2—
wherein Rg is a hydrogen atom or C1-6 alkyl-sulfonyl group and m2 is 0,(xvii) a group represented by Formula —
SO2—
NRh—
(CH2)m3—
wherein Rh is a hydrogen atom or C1-6 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 C1-6 alkyl group and m4 is 0 or 1,(xix) a group represented by Formula —
NRj—
CO—
NRk—
(CH2)m5—
wherein Rj is a hydrogen atom or C1-6 alkyl group, Rk is a hydrogen atom or C1-6 alkyl group and m5 is 0 or 1,(xx) a group represented by Formula —
NRL—
CO—
CH2—
(CH2)m6—
—
NRm—
wherein RL is a hydrogen atom or C1-6 alkyl group, Rm is a hydrogen atom or C1-6 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 R1b 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—
, —
NR1C—
CO—
(CH2)m—
, —
NR1C—
SO2—
(CH2)m—
, —
SO2—
NR1C—
(CH2)m—
, —
O—
CS—
NR1C—
(CH2)m—
, —
NR1C—
CO—
NR1C—
(CH2)m—
, —
NR1C—
CO—
(CH2)m—
NR1C—
wherein R1C 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;
—
OR4′
wherein R4′
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 C1-6 alkyl group(s) and n is 0 or 1.
-
-
11. The compound according to claim 1 wherein R1 is, (i) a C6-14 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 C1-6alkyl group [this C1-6 alkyl group may have a substituent selected from a halogen atom, cyano, carbamoyl, C1-6 alkyl-carbamoyl, C1-6 alkyl-carbonyloxy, C1-6 alkoxy-carbonyl-C1-6 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)-C1-6 alkyl-carbamoyl, C1-6 alkylsulfonylamino, C1-6 alkoxy-carbonyl and carboxy], (4) a C3-6 cycloalkyl group, (5) a C6-14 aryl group [this C6-14 aryl group may have a substituent selected from amino, carboxy, C1-6 alkoxy-carbonyl, carbamoyl, mono- or di-C1-6 alkylcarbamoyl, formylamino, C1-6 alkyl-carbonylamino which may have a halogen atom or carboxy, C6-14 aryl-carbonylamino, C1-6 alkoxy-carbonylammo, ureido, mono- or di-C1-6 alkylureido, C1-6 alkylsulfonylamino, (C1-6 allcyl)(C1-6 alkylsulfonyl) amino, (C1-6alkyl)(C1-6 alkyl-carbonyl) amino, C1-6 alkoxy-carbonyl-C1-6 alkylamino, C6-14 aralkyloxy-carbonylamino, C1-6 alkyl-carbonylamino-C1-6 alkyl-carbonylamino, C1-6 allcylthio-C1-6 alkyl-carbonylamino, C1-6 alkyl-sulfinyl-C1-6 alkyl-carbonylamino, C1-6 alkyl-sulfonyl-C1-6 alkyl-carbonylamino, C6-14 aryloxy-carbonylamino and hydroxy-C1-6 alkyl-carbamoyl], (6) a C1-6 alkoxy group which may have a halogen atom or C1-6 alkoxy-C6-14 aryl, (7) a C6-14 aryloxy group, (8) a C1-6 alkylthio group which may have a carbamoyl, (9) a C1-6 alkylsulfinyl group which may have a carbamoyl, (10) a C6-14 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-C1-6 alkyl, C1-6 alkyl-carbonyloxy-C1-6 alkyl, C1-6 alkyl, C1-6 alkoxy-carbonyl-C1-6 alkyl, C,6 alkoxy-carbonyl, carbamoyl-C1-6 alkyl and C1-6 allcyl-carbamoyl-C1-6 alkyl], (13) a carboxy group, (14) a group represented by Formula;
—
CO—
Hal (wherein Hal is a halogen atom),(15) a C1-6 alkyl-carbonyl group, (16) a C1-6 alkyl-sulfonyl group, (17) a C1-6 alkoxy-carbonyl group, (18) a sulfamoyl group [this sulfamoyl group may have 1 or 2 substituent(s) selected from C1-6 alkyl, carbamoyl-C1-6 alkyl, C1-6 alkoxy-carbonyl-C1-6 alkyl, (5- to 8-membered heterocyclic ring which may have an oxo group)-C1-6 alkyl and C1-6 alkyl-carbonylamino-C6-14 aryl], (19) a group represented by Formula;
—
NRaRb [each of Ra and Rb is (i) a hydrogen atom, (ii) a C1-6 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)-C1-6 alkyl, (iv) a C1-6 alkoxy-carbonyl-C1-6 alkyl, (v) a di-C1-6 alkylamino-methylene-sulfamoyl-C1-6 alkyl, (vi) a carbamoyl-C1-6 alkyl, (vii) a sulfamoyl-C1-6 alkyl, (viii) a C1-6 alkyl-sulfonyl, (ix) a C1-6 alkoxy-carbonyl, (x) a di-C1-6 alkoxy-carbonyl-C2-6 alkenyl, (xi) a C6-14 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, C1-6 alkyl-carboxamido and C1-6 alkyl-sulfonylamino], (xiii) an optionally halogenated-C1-6 alkyl-carbonyl, (xiv) a C1-6 alkylthio-C1-6 alkyl-carbonyl, (xv) a C1-6 4 alkylsulfinyl-C1-6 alkyl-carbonyl, (xvi) a C1-6 alkylsulfonyl-C1-6 alkyl-carbonyl, (xvii) an amino-C1-6 alkyl-carbonyl, (xviii) an optionally halogenated C1-6 alkyl-carbonyl-amino-C1-6 alkyl-carbonyl, (xix) a C1-6 aryl-carbonyl, (xx) a carboxy-C6-14 aryl-carbonyl, (xxi) an optionally C1-6 alkyl-esterified phosphono-C1-6 alkyl-C1-6 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 C1-6 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)-C1-6 alkyl-carbonyl, (xxiv) a C6-14 aryl-oxy-carbonyl, (xxv) a carboxy-C1-6 alkyl, (xxvi) a carbamoyl, (xxvii) an optionally halogenated C1-6 alkylcarbamoyl, (xxviii) a C6-14 arylcarbamoyl which may have a C1-6 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 C2-6 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-C1-6 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)(C1-6 alkyl) amino-C1-6 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)(C1-6 alkylcarbonyl) amino-C1-6 alkyl-carbonyl, (xxxiv) a C1-6 alkylthio-C1-6 alkylcarbonyl (sulfur atom may be oxidized), (xxxv) an optionally halogenated C1-6 alkylsulfonyl, (xxxvi) a sulfamoyl or (xxxvii) a C1-6 alkylsulfamoyl],(20) a group represented by Formula;
—
C(═
O)NRcRd [each of Rc and Rd is (i) a hydrogen atom, (ii) a C1-6 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)-C1-6 alkyl, (iv) a carboxy-C145alkyl, (v) a C1-6 alkoxy-carbonyl-C1-6 alkyl, (vi) a di-C1-6 alkylamino-C1-6 alkyl, (vii) a carbamoyl-C1-6 alkyl, (viii) a C1-6 alkylcaxbamoyl-C1-6 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)-C1-6 alkylcarbamoyl-C1-6 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-C1-6 alkyl, (xi) a sulfamoyl-C6-14 aryl-C1-6 alkyl, (xii) a C6-14 aryl which may have a C1-6 alkoxy, (xiii) an optionally C1-6 alkyl-esterified phosphono-C1-6 alkyl-C6-14 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, C1-6 alkyl and oxo], (xv) a C6-14 aryl-carbamoyl-C1-6 alkyl, (xvi) a hydroxy-C1-6 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-C1-6 alkyl],(21) a cyano group, (22) a mono- or di-C1-6 alkylcarbamoylthio group, (23) a mono- or di-C1-6 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 C1-6 alkyl group [this alkyl may have a substituent selected from carboxy, C1-6 alkoxy, C1-6 alkoxy-carbonyl, mono-C1-6 alkyl-amino, di-C1-6 alkyl-amino, carbamoyl, C1-6 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-C1-6 alkyl-carbamoyl], (3) a C1-6 alkoxy group, (4) a C6-14 aryl group, (5) a C7-16 aralkyl group [this C7-16 aralkyl group may have a substituent selected from carboxy, C1-6 alkoxy-carbonyl, carbamoyl, C1-6 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 C1-6 alkyl, C1-6 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 C3-6 cycloalkyl group;
or,(iv) a group represented by Formula;
—
L′
—
R1a (L′
is methylene, carbonyl or an optionally substituted nitrogen atom, R1a′
is (1) a hydrogen atom, (2) a C6-14 aryl group which may have 1 to 5 substituent(s) selected from a C1-6 alkyl and C1-6 alkoxy, (3) a hydroxy group which may be substituted by a C1-6 alkyl group, (4) a C1-6 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 C6-14 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 C1-6 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 C1-6 alkyl, C1-6 alkyl-carbonyl, C1-6 alkylsulfonyl and C7-16 aralkyl, <
3>
an amino group which may be substituted by 1 or 2 C1-6 alkyl, C3-6 alkyl-carbonyl and C6-14 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 C1-6 alkyl, <
6>
a C1-6 alkyl-sulfinyl group or <
7>
a C1-6 alkyl-sulfonyl group, or (3) a C1-6 alkoxy-carbonyl group,R2 and R3 may be taken together with the adjacent carbon atom to form a C3-8 cycloalkane, R4 is (i) a hydrogen atom, (ii) a cyano group, (iii) a C1-6 alkyl group [this C1-6 alkyl group may have a substituent selected from (1) a halogen atom, (2) a cyano group, (3) a C1-6 alkoxy group, (4) a hydroxy group, (5) an amino group, (6) a mono-C1-6 alkylamino group, (7) a di-C1-6 alkylamino group, (8) a tri-C1-6 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 C6-14 arylthio, (10) an ureido, (11) a carboxy, (12) a carbamoyl, (13) a C1-6 alkoxy-carbonyl, (14) a mono-C1-6 alkyl-carbamoyl, (15) a formylamino and (16) a C1-6 alkyl-carboxamide], (iv) a C2-6 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 C1-6 alkyl group or (iii) a halogen atom, when X is an oxygen atom, then (i) a hydrogen atom, (ii) a C1-6 alkyl group [this C1-6 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 C1-6 alkoxy-carbonyl, (7) a mono-C1-6 alkyl-carbamoyl, (8) a di-C1-6 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 C2-6 alkenyl group [this C2-6 alkenyl group may have a C1-6 aryl], (iv) a C2-6 alkynyl group, (v) a C3-6 cycloalkyl group, (vi) a C7-16 aralkyl group, (vii) a C1-6 alkyl-carbonyl group, (viii) a C6-14 aryl-carbonyl group, (ix) a C1-6 alkoxy-carbonyl group, (x) a mono- or di-C1-6 alkyl-thiocarbamoyl group, (xi) an optionally halogenated C1-6 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 C6-14 aryl], when X is an optionally oxidized sulfur, then (i) a C1-6 alkyl group or (ii) a mono- or di-C1-6 alkyl-carbamoyl group, when X is —
NH—
or —
N(methyl)-, then (i) a hydrogen atom, (ii) a C1-6 alkyl group [this C1-6 alkyl group may have a C1-6 alkoxy-carbonyl], (iii) formyl, (iv) a C1-6 alkyl-carbonyl group, (v) a C1-6 alkoxy-carbonyl group, (vi) a carbamoyl group, (vii) a mono- or di-C1-6 alkyl-carbamoyl group or (viii) a C1-6 alkyl-sulfonyl group,each of R6 and R7 is a hydrogen atom or C1-6 alkyl group, R6 and R7 may be taken together with the adjacent carbon atom to form a C3-8 cycloalkane, Each of R8 and R9 is a hydrogen atom or a C1-6 alkyl group, Y is <
1>
a methylene group which may have 1 or 2 C1-6 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 C6-14 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 C1-6 alkyl group [this C1-6 alkyl group may have a substituent selected from a halogen atom, cyano, carbamoyl, C1-6 alkyl-carbamoyl, C1-6 alkyl-carbonyloxy, C1-6 alkoxy-carbonyl-C1-6 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)-C1-6 alkyl-carbamoyl, C1-6 alkylsulfonylamino, C1-6 alkoxy-carbonyl and carboxy], (4) a C3-6 cycloalkyl group, (5) a C6-14 aryl group [this 06-14 aryl group may have a substituent selected from amino, optionally halogenated C1-6 alkyl-carbonylamino, ureido, C1-6 alkylsulfonylamino, (C1-6 alkyl)(C1-6 alkylsulfonyl) amino, C1-6 alkoxy-carbonyl-C1-6 alkylamino], (6) a C1-6 alkoxy group which may have a halogen atom or C1-6 alkoxy-C6-14 aryl, (7) a C6-14 aryloxy group, (8) a C1-6 alkylthio group, (9) a C1-6 alkylsulfinyl group, (10) a C6-14 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-C1-6 alkyl, C1-6 alkyl-carbonyloxy-C1-6 alkyl, C1-6 alkoxy-carbonyl-C1-6 alkyl, C1-6 alkyl-carbamoyl-C1-6 alkyl], (13) a carboxy group, (14) a group represented by Formula;
—
CO—
Hal (Hal is a halogen atom),(15) a C1-6 alkyl-carbonyl group, (16) a C1-6 alkyl-sulfonyl group, (17) a C1-6 alkoxy-carbonyl group, (18) a sulfamoyl group [this sulfamoyl group may have a substituent selected from C1-6 alkyl, carbamoyl-C1-6 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)-C1-6 alkyl], (19) a group represented by Formula;
—
NRaRb [each of Ra and Rb is (i) a hydrogen atom, (ii) a C1-6 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)-C1-6 alkyl, (iv) a C1-6 alkoxy-carbonyl-C1-6 alkyl, (v) a di-C1-6 alkylamino-methylene-sulfamoyl-C2-6 alkyl, (vi) a carbamoyl-C1-6 alkyl, (vii) a sulfamoyl-C1-6 alkyl, (viii) a C1-6 alkyl-sulfonyl, (ix) a C1-6 alkoxy-carbonyl, (x) a di-C1-6 alkoxy-carbonyl-C1-6 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, C1-6 alkyl-carboxamido and C1-6 alkyl-sulfonylamino], (xiii) an optionally halogenated C1-6 alkyl-carbonyl, (xiv) a C1-6 alkylthio-C1-6 alkyl-carbonyl, (xv) a C1-6 alkylsulfinyl-C1-6 alkyl-carbonyl, (xvi) a C1-6 alkylsulfonyl-C1-6 alkyl-carbonyl, (xvii) an amino-C1-6 alkyl-carbonyl, (xviii) an optionally halogenated C1-6 alkyl-carbonyl-amino-C1-6 alkyl-carbonyl, (xix) a C6-14 aryl-carbonyl, (xx) a carboxy-C6-14 aryl-carbonyl, (xxi) an optionally C1-6 alkyl-esterified phosphono-C1-6 alkyl-C6-14 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 C1-6 alkoxy-carbonyl)-C1-6 alkyl-carbonyl, (xxiv) a C6-14 aryl-oxy-carbonyl, (xxv) a carboxy-C1-6 alkyl or (xxvi) a carbamoyl],(20) a group represented by Formula;
—
C(═
O)NRcRd [each of Rc and Rd is (i) a hydrogen atom, (ii) a C1-6 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)-C1-6 alkyl, (iv) a carboxy-C1-6 alkyl, (v) a C1-6 alkoxy-carbonyl-C1-6 alkyl, (vi) a di-C1-6 alkylamino-C1-6 alkyl, (vii) a carbamoyl-C1-6 alkyl, (viii) a C1-6 alkylcarbamoyl-C1-6 alkyl, (ix) a (5- or 6-membered heterocyclic group containing 1 to 3 heteroatom(s) selected from nitrogen, sulfur and oxygen atoms)-C1-6 alkyl carbamoyl-C1-6 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-C1-6 alkyl, (xi) a sulfamoyl-C6-14 aryl-C1-6 alkyl, (xii) a C6-14 aryl which may have a C1-6 alkoxy, (xiii) a C1-6 alkyl-C1-14 aryl which have an optionally C1-6 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, C1-6 alkyl and oxo] or (xv) a C6-14 aryl-carbamoyl-C1-6 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 C1-6 alkyl group [this alkyl may have a substituent selected from carboxy, C1-6 alkoxy, C1-6 alkoxy-carbonyl, mono-C1-6 alkyl-amino, di-C1-6 alkyl-amino, carbamoyl, C1-6 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-C1-6 alkyl-carbamoyl], (3) a C1-6 alkoxy group, (4) a C6-14 aryl group, (5) a C7-16 aralkyl group [this C7-16 aralkyl group may have a substituent selected from carboxy, C1-6 alkoxy-carbonyl, carbamoyl, C1-6 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 C1-6 alkyl, C1-6 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 C3-6 cycloalkyl group;
or,(iv) a group represented by Formula;
—
L′
—
R1a (L′
is methylene, carbonyl or —
NH—
, R1a is (1) a hydrogen atom, (2) a C6-14 aryl group which may have 1 to 5 substituent(s) selected from a C1-6 alkyl and C1-6 alkoxy, (3) a hydroxy group which may be substituted by a C1-6 alkyl group, (4) a C1-6 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 C6-14 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 C1-6 alkyl group or (3) a C1-6 alkoxy-carbonyl group, R2 and R3 may be taken together with the adjacent carbon atom to form a C3-8 cycloalkane, R4 is (i) a hydrogen atom, (ii) a C1-6 alkyl group [this C1-6 alkyl group may have a substituent selected from (1) a halogen atom, (2) a cyano group, (3) a C1-6 alkoxy group, (4) a hydroxy group, (5) an amino group, (6) a mono-C1-6 alkylamino group, (7) a di-C1-6 alkylamino group, (8) a tri-C1-6 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 C6-14 arylthio, (11) an ureido, (12) a carboxy, (13) a carbamoyl, (14) a C1-6 alkoxy-carbonyl, (15) a mono-C1-6 alkyl-carbamoyl, (16) a formylamino, (17) a C1-6 alkyl-carboxamido] or (iii) a C2-6 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 C1-6 alkyl group or (iii) a halogen atom, when X is an oxygen atom, then (i) a hydrogen atom, (ii) a C1-6 alkyl group [this C1-6 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 C1-6 alkoxy-carbonyl, (7) a mono-C1-6 alkyl-carbamoyl, (8) a di-C1-6 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 C2-6 alkenyl group [this C2-6 alkenyl group may have a C6-14 aryl], (iv) a C2-6 alkynyl group, (v) a C3-6 cycloalkyl group, (vi) a C7-16 aralkyl group, (vii) a C1-6 alkyl-carbonyl group, (viii) a C6-14 aryl-carbonyl group, (ix) a C1-6 alkoxy-carbonyl group, (x) a mono- or di-C1-6 alkyl-thiocarbamoyl group, (xi) an optionally halogenated C1-6 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 C6-14 aryl], when X is a sulfur, then (i) a C1-6 alkyl group or (ii) a mono- or di-C1-6 alkyl-carbamoyl group, when X is —
NH—
or —
N(methyl)-, then (i) a hydrogen atom, (ii) a C1-6 alkyl group [this C1-6 alkyl group may have a C1-6 alkoxy-carbonyl], (iii) formyl, (iv) a C1-6 alkyl-carbonyl group, (v) a C1-6 alkoxy-carbonyl group, (vi) a carbamoyl group, (vii) a mono- or di-C1-6 alkyl-carbamoyl group or (viii) a C1-6 alkyl-sulfonyl group,each of R6 and R7 is a hydrogen atom or C1-6 alkyl group, R6 and R7 may be taken together with the adjacent carbon atom to form a C3-8 cycloalkane, each of R8 and R9 is a hydrogen atom or a C1-6 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 C1-6 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 C1-6 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.
- reacting a compound represented by Formula;
-
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.
- N—
Specification