JP2006520373A5

JP2006520373A5 -

Info

Publication number: JP2006520373A5
Application number: JP2006505952A
Authority: JP
Filing date: 2004-03-12
Publication date: 2007-04-19

Claims

Formula I

[In the above formula,
R ¹ represents an aryl group or a heteroaryl group, both of which represent a group that may be substituted by one or more substituents selected from G ¹ and B ¹ , and the B ¹ group itself is G ² , Z (wherein Z is not directly bonded to an aryl or heteroaryl group) and B ² (wherein the B ² group is substituted by one or more substituents selected from G ³ , B ³ and Z) Which may be further substituted, provided that Z is not directly attached to an aryl or heteroaryl group) and may be further substituted with one or more substituents selected from:
R ² represents H or C _1-6 alkyl, the latter group optionally substituted by one or more halo groups;
Or
When R ² represents C _1-6 alkyl optionally substituted by halo, R ¹ and R ² are bonded together and contain 1 to 3 heteroatoms and / or 1 to 3 double bonds. May form a further 5- to 7-membered ring, which itself is G ¹ , Z (where the ring is not aromatic) and B ¹ (where the B ¹ group is substituted as described above) Any one of which may be substituted with one or more substituents selected from:
R ³ is C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl, C _3-8 heterocycloalkyl, aryl or heteroaryl, all groups of which are G ^{One selected from 1a} , Z (wherein Z is not directly bonded to an aryl or heteroaryl group) and B ¹ (the B ¹ group is not directly bonded to an aryl or heteroaryl group); Or represents a group which may be substituted by a plurality of substituents;
X represents a direct bond, —O— or —N (R ⁴ ) —;
Y represents —C (O) —, —C (S) — or —S (O) ₂ —;
B ¹ , B ² and B ³ are, independently in each case used above, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl, C _3-8 represents heterocycloalkyl, aryl or heteroaryl,
G ¹ , G ^1a , G ² and G ³ each independently represent halo, cyano, —N ₃ , —NO ₂ , —ONO ₂ or —A ¹ —R ⁴ in each case used above. Representation;
Here, A ¹ is a spacer group selected from —C (Z) A ² —, —N (R ⁵ ) A ³ —, —OA ⁴ —, —S— or —S (O) _n A ⁵ —. Where
A ² represents a single bond, —O—, —S— or —N (R ⁵ ) —;
A ³ represents A ⁶ , —C (Z) N (R ⁵ ) C (Z) N (R ⁵ ) —, —C (Z) N (R ⁵ ) C (Z) O—, —C (Z) N (R ⁵ ) S (O) _n N (R ⁵ )-, -C (Z) S-, -S (O) _n- , -S (O) _n N (R ⁵ ) C (Z) N ( ^{R 5) -, - S (} O) n n (R 5) C (Z) O -, - S (O) n n (R 5) S (O) n n (R 5) -, - C (Z ) O—, —S (O) _n N (R ⁵ ) — or —S (O) _n O—;
A ⁴ represents A ⁶ , —S (O) _n —, —C (Z) O—, —S (O) _n N (R ⁵ ) —, or —S (O) _n O—;
A ⁵ represents a single bond, —N (R ⁵ ) — or —O—;
A ⁶ represents a single bond, —C (Z) — or —C (Z) N (R ⁵ ) —;
Z is, in each case used above, = O, = S, = NR ⁴ , = NN (R ⁴ ) (R ⁵ ), = NOR ⁴ , = NS (O) ₂ N (R ⁴ ) ( Represents a substituent linked by a double bond selected from R ⁵ ), = NCN, ═CHNO ₂ and ═C (R ⁴ ) (R ⁵ );
R ⁴ and R ⁵ each independently represents H or B ⁴ in each case used above, wherein the B ⁴ group itself is G ⁴ , Q (where Q is directly connected to an aryl or heteroaryl group) One or more selected from B ⁵ (the B ⁵ group itself is G ⁵ , Q (where Q is not directly bonded to an aryl or heteroaryl group)) and B ⁶ When R ⁴ and R ⁵ together represent a B ⁴ group that may be substituted, and may be substituted by one or more substituents selected from The optional pairs are bonded to each other, for example when present on the same atom or adjacent atoms, and together with these or other related atoms, have 1-3 heteroatoms and / or 1-3 double bonds. Forming a 5- to 7-membered ring that may contain Ku, the ring itself G ^6, Q (provided that the ring is not aromatic) and B ^{4 (the} B ⁴ groups may be substituted as described above) one or more selected from Optionally substituted by a substituent;
B ⁴ , B ⁵ and B ⁶ are, independently in each case used above, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl, C _3-8 represents heterocycloalkyl, aryl or heteroaryl,
G ⁴ , G ⁵ and G ⁶ each independently represent halo, cyano, —N ₃ , —NO ₂ , —ONO ₂ or —A ⁷ —R ⁶ in each case used above;
Here, ^{A 7} ^{is, -C (Q) A 8 -} , - N (R 7) A 9 -, - N (R 7a) A 9a -, - OA 10 -, - S- or -S (O) _{n a} 11 ^- represents a spacer group selected from, wherein
A ⁸ represents a single bond, —O—, —S— or —N (R ⁷ ) —;
A ⁹ is A ¹² , —C (Q) S—, —S (O) _n —, —C (Q) O—, —S (O) _n N (R ⁷ ) — or —S (O) _n Represents O-;
A ^9a is -C (Q) N (R ⁷ ) C (Q) N (R ⁷ )-, -C (Q) N (R ⁷ ) C (Q) O-, -C (Q) N (R ^{_{7) S (O) n n}} (R 7) -, - S (O) n n (R 7) C (Q) n (R 7) -, - S (O) n n (R 7) C (Q ) O -, - S (O ) n n (R 7) S (O) n n (R 7) - it represents;
A ¹⁰ represents A ¹² , —S (O) _n —, —C (Q) O—, —S (O) _n N (R ⁷ ) —, or —S (O) _n O—;
A ¹¹ represents a single bond, —N (R ⁷ ) — or —O—;
A ¹² represents a single bond, —C (Q) — or —C (Q) N (R ⁷ ) —;
Q is, in each case used above, = O, = S, = NR ⁶ , = NN (R ⁶ ) (R ⁷ ), = NOR ⁶ , = NS (O) ₂ N (R ⁶ ) ( R ⁷ ), = NCN, = CHNO ₂ and = C (R ⁶ ) (R ⁷ ) represents a substituent linked by a double bond selected from;
R ⁶ , R ⁷ and R ^7a are, in each case used above, independently H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl , C _3-8 heterocycloalkyl, aryl or heteroaryl, the last seven groups being halo, C _1-6 alkyl (optionally substituted with one or more halo groups), —N (R ⁸ ) optionally substituted with one or more groups selected from R ⁹ , —OR ⁸ , —ONO ₂ and —SR ⁸ ; or, if they do not represent H, R ⁶ and R ⁷ Any pair is bound to each other, for example when present on the same atom or adjacent atoms, and together with these or other related atoms, contains 1-3 heteroatoms and / or 1-3 double bonds. May form a 5- to 7-membered ring, , _{C 1-6} alkyl (optionally substituted with one or more halo ^{groups), - N (R 8)} R 9, -OR 8, one or more selected from -ONO _2, and -SR ⁸ Optionally substituted with a group;
R ⁸ and R ⁹ in each case used above independently represent H or C _1-6 alkyl, the latter group optionally substituted by one or more halo groups;
n represents 1 or 2 in each case used above, or a pharmaceutically acceptable salt thereof,
Where R ² represents H, Y represents —C (O) —, and:
(A) X represents a direct bond and:
i) when R ³ represents phenyl, R ¹ does not represent phenyl, 2-methoxyphenyl, 2-thiazolyl or 6-methyl-2-pyridinyl;
ii) when R ³ represents 4-fluorophenyl, R ¹ does not represent 2-carbomethoxyphenyl, 3-carbomethoxyphenyl or 2,4-dimethylphenyl;
iii) when R ³ represents 2-chlorophenyl, R ¹ does not represent phenyl, 3-bromophenyl or 4-bromophenyl;
iv) when R ³ represents 3-chlorophenyl, R ¹ does not represent phenyl, 2-fluorophenyl, 2-chlorophenyl, 2,3-dichlorophenyl or 2,5-dichlorophenyl;
v) when R ³ represents 4-chlorophenyl, R ¹ does not represent 3-bromophenyl or 4-methoxyphenyl;
vi) when R ³ represents 3-iodophenyl, R ¹ does not represent 2-methoxyphenyl or 2,4-dimethylphenyl;
vii) when R ³ represents 2,4-dichlorophenyl, R ¹ does not represent 4-chlorophenyl or 2,3-dichlorophenyl;
viii) when R ³ represents 3,5-dinitrophenyl, R ¹ does not represent 2,3-dichlorophenyl;
ix) when R ³ represents 2,4-dimethyl-6-oxo-6H-pyran-3-yl, R ¹ does not represent 3-carbomethoxyphenyl;
x) when R ³ represents methyl, R ¹ represents 3,4-dichlorophenyl, 2-methoxyphenyl, 2-thiazolyl, 4-methyl-2-pyridinyl, 6-methyl-2-pyridinyl or 4-acetylphenyl Sazu;
xi) when R ³ represents ethyl, R ¹ does not represent 2,3-dichlorophenyl, 4-methoxyphenyl, 2-carbomethoxyphenyl, 2-thiazolyl or 4-methyl-2-pyridinyl;
(B) X represents —N (H) — and:
i) when R ³ represents phenyl, R ¹ does not represent 4-methoxyphenyl, 2,4-dimethylphenyl or 2-thiazolyl;
ii) when R ³ represents 3-chlorophenyl, R ¹ does not represent 4-methylphenyl;
iii) when R ³ represents 4-chlorophenyl, R ¹ does not represent 3-bromophenyl;
iv) when R ³ represents 3,4-dichlorophenyl, R ¹ does not represent 4-methyl-2-pyridinyl or 6-methyl-2-pyridinyl;
v) when R ³ represents 2′-sulfamoylbiphenyl-4-yl, R ¹ does not represent 5-bromo-2-pyridinyl;
vi) when R ³ represents 1-propyl, R ¹ does not represent phenyl;
vii) when R ³ represents 1-butyl, R ¹ does not represent 4-bromophenyl or 2,4-dimethylphenyl;
viii) when R ³ represents cyclohexyl, R ¹ does not represent 4-methoxyphenyl;
(C) X represents —O— and:
i) when R ³ represents phenyl, R ¹ does not represent phenyl or 6-methyl-2-pyridinyl;
ii) when R ³ represents methyl, R ¹ does not represent phenyl, 2-fluorophenyl, 2,4-dimethylphenyl, 4-acetylphenyl or 2-thiazolyl;
iii) when R ³ represents ethyl, R ¹ does not represent phenyl, 2-fluorophenyl, 4-acetylphenyl or 4-methyl-2-pyridinyl;
iv) when R ³ represents 1-butyl, R ¹ does not represent 2-fluorophenyl, 2-methoxyphenyl, 4-methyl-2-pyridinyl or 6-methyl-2-pyridinyl;
v) when R ³ represents 2-butyl, R ¹ does not represent 2-thiazolyl or 4-acetylphenyl;
vi) A compound in which when R ³ represents 2-methyl-1-propyl, R ¹ does not represent phenyl or 3-nitrophenyl.

2. A compound according to claim 1, wherein R < ¹ > represents an aryl or heteroaryl group, both groups optionally substituted as defined in claim 1.

G ¹ is represented halo, cyano or -A ¹ -R ^4, A compound according to claim 1 or 2.

The B ¹ represents an optionally substituted C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-7 cycloalkyl, C _4-7 heterocycloalkyl, or phenyl group. The compound according to any one of 1 to 3.

The compound according to any one of claims 1 to 4, wherein G ^1a represents halo, cyano, -NO ₂ or -A ¹ -R ⁴ .

G ² is halo, cyano, represents a -ONO ₂ or -A ¹ -R ^4, A compound according to any one of claims 1 to 5.

B ² represents C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl, all of which may be substituted with one or more G ³ and / or B ³ groups. 7. The compound according to any one of 6.

G ³ is _{^{halo, -ONO 2, -N (R 5}} ) (R 4) or an -OR ^4, A compound according to any one of claims 1 to 7.

B ³ represents _{C 1-6} _{alkyl, C 2-6} alkenyl or _{C 2-6} alkynyl, A compound according to any one of claims 1 to 8.

A ¹ represents —N (R ⁵ ) A ³ —, and A ³ represents A ⁶ , —C (Z) S—, —S (O) _n —, —C (Z) O— or —S (O) _{n n} (R ⁵⁾ - represents a compound according to any one of claims 1 to 9.

The compound according to any one of claims 1 to 9, wherein A ¹ represents -OA ^4- and A ⁴ represents A ⁶ .

The compound according to any one of claims 1 to 9, wherein A ¹ represents -S (O) _n A ^5- , and A ^5- represents a single bond or -N (R ⁵ )-.

The compound according to any one of claims 1 to 9, wherein A ¹ represents -C (Z) A ^2- , and A ^2- represents a single bond, -O- or -N (R ⁵ )-.

A ¹ is ^{-C (Z) A 2 -,} - N (R 5) A 3 - or -OA 4 ^- a representative compound according to any one of claims 1 to 11 or 13.

Z represents a is = O or = NR ^4, a compound according to any one of claims 1 to 14.

If any pair of R ⁴ and R ⁵ form a ring together, they may be substituted with G ⁶ and / B ^4, according to any one of claims 1 to 15 Compound.

G ⁴ is halo, cyano, -ONO represents ₂ or -A ⁷ -R ^6, A compound according to any one of claims 1 to 16.

18. Any one of claims 1 to 17, wherein B ⁵ represents C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl, all of which may be substituted with G ⁵ and / or B ⁶ groups. A compound according to one paragraph.

G ⁵ is _{^{halo, -ONO 2, -N (R 7}} ) (R 6) or an -OR ^6, compounds according to any of claims 1 to 18.

B ⁶ represents _{C 1-6} _{alkyl, C 2-6} alkenyl or _{C 2-6} alkynyl, A compound according to any one of claims 1 to 19.

G ⁶ represents halo, cyano or -A ⁷ -R ^6, A compound according to any one of claims 1 to 20.

A ⁷ is ^{-C (Q) A 8 -,} - N (R 7) A 9 -, - OA 10 -, - S- or -S (O) _n A ^{11 -} represents the, any of claims 1 to 21 A compound according to claim 1.

When A ⁷ represents —N (R ⁷ ) A ⁹ —, A ⁹ represents A ¹² , —C (Q) S—, —S (O) _n —, —C (Q) O— or —S (O ⁾ _{n n} (R ⁷⁾ - a representative compound according to any one of claims 1 to 22.

A ⁷ is -OA ^{10 -} when referring ^{to, A 10} represents ^{A 12,} A compound according to any one of claims 1 to 22.

When referring ^{to, A 11} is a single bond or ^{^{-N (R 7) - - A}} 7 is -S (O) _n A ¹¹ a represents A compound according to any one of claims 1 to 22.

When referring to, A ⁸ is a single bond, -O- or ^{^{-N (R 7) - - A}} 7 is -C (Q) A 8 a represents A compound according to any one of claims 1 to 22.

Q represents a is = O or = NR ^6, A compound according to any one of claims 1 to 26.

R ⁶ , R ⁷ and R ^7a independently represent H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl, all of which groups are halo, C _1-6 alkyl, —N The compound according to any one of claims 1 to 27, which may be substituted with one or more groups selected from (R ⁸ ) R ⁹ , -OR ⁸ and -ONO ₂ .

Any pair of R ⁶ and R ⁷ can be joined together to form a ring that is halo, C _1-6 alkyl (optionally substituted with one or more halo groups), —N ( R ⁸⁾ R ^9, which may be substituted with one or more groups selected from -OR ⁸ and -ONO _2, a compound according to any one of claims 1 to 27.

The B ⁴ represents an optionally substituted C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-8 cycloalkyl, C _4-7 heterocycloalkyl, or phenyl group. 30. The compound according to any one of 1 to 29.

31. According to any one of claims 1 to 30, wherein R ⁴ and / or R ⁵ independently represents H or C _1-6 alkyl, the latter group optionally substituted with one or more fluoro groups. The described compound.

The compound according to any one of claims 1 to 31, wherein X represents a direct bond, -O-, -N (H)-or -N (Me)-.

R ² represents H, methyl or ethyl, A compound according to any one of claims 1 to 32.

R ¹ may be substituted phenyl, naphthyl, pyrrolidinyl, piperidinyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, indazolyl, indolyl, indolinyl, isoindolinyl, oxyindolyl, quinolinyl, 1 , 2,3,4-tetrahydroquinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, quinolidinyl, benzofuranyl, isobenzofuranyl, chromanyl, benzothiophenyl, pyridazinyl, pyrimidinyl, pyrazinyl, indazolyl 34. Represents a benzimidazolyl, quinazolinyl, quinoxalinyl, 1,3-benzodioxolyl, benzothiazolyl or benzodioxanyl group according to any one of claims 1, 32 or 33. Compound of the mounting.

R ¹ represents an optionally substituted phenyl, 2-pyridinyl, 3-pyridinyl, 2-thiophenyl, 4-pyrazolyl, 5-isoxazolyl, 1,3-benzodioxolyl, indazolyl, benzothiazolyl, or quinolinyl group; 35. The compound of claim 34.

Optional substituents are halo, cyano, C _1-6 alkyl (wherein the alkyl is linear or branched and / or substituted with one or more fluoro and / or C _3-6 cycloalkyl groups) C _2-6 alkenyl, C _3-6 cycloalkyl, phenyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, thiomethyl, methylsulfinyl, methylsulfonyl, —OR ¹⁰ , —N (R) ¹⁰ ) R ¹¹ , —C (O) OR ¹⁰ , —C (O) R ¹⁰ , —C (O) N (R ¹⁰ ) R ¹¹ , —S (O) ₂ N (R ¹⁰ ) R ¹¹ and —N (R ¹⁰ ) S (O) ₂ R ¹² {where R ¹⁰ and R ¹¹ are independently H, phenyl, C _1-6 alkyl (wherein the alkyl may be substituted with one or more fluoro atoms) ), C _2-6 R represents alkenyl or C _3-6 cycloalkyl; or R ¹⁰ and R ¹¹ are bonded to each other and may contain one additional heteroatom with the nitrogen atom to which they are bonded, and one or more C _It may form a 5- to 7-membered ring optionally substituted with a _1-6 alkyl group, and the alkyl group itself may be substituted with one or more halo groups; R ¹² is phenyl, C _{1 35. selected from -6} alkyl (which may be substituted with one or more fluoro atoms), C _2-6 alkenyl or C _3-6 cycloalkyl}. Or the compound according to 35.

37. The compound of claim 36, wherein the optional substituent is selected from carbomethoxy, methyl, dimethylamino, cyano, chloro, fluoro, trifluoromethyl, bromo, methoxy and trifluoromethoxy.

R ³ optionally substituted C _1-6 alkyl, C _3-6 cycloalkyl, phenyl, naphthyl, pyrrolidinyl, piperidinyl, piperazinyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, Indazolyl, indolyl, indolinyl, isoindolinyl, oxyindolyl, quinolinyl, 1,2,3,4-tetrahydroquinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, quinolidinyl, benzofuranyl, isobenzofuran Nyl, chromanyl, benzothiophenyl, pyridazinyl, pyrimidinyl, pyrazinyl, indazolyl, benzimidazolyl, quinazolinyl, quinoxalinyl, 1,3-benzodioxolyl, benzothiazolyl, or benzodi 38. A compound according to any one of claims 1 or 32 to 37 which represents an oxanyl group.

R ³ may be optionally substituted C _1-6 alkyl, cyclohexyl, phenyl, 2-thiophenyl, 2-furanyl, 3-furanyl, 2-pyrrolyl, 1-naphthyl, 4-piperazinyl, 4-piperidinyl, benzofuranyl, or 39. A compound according to claim 38, which represents a 1,3-benzodioxolyl group.

Optional substituents are halo, —NO ₂ , cyano, C _1-6 alkyl (wherein the alkyl is linear or branched, and / or one or more halo, C _1-6 alkyl, C _2-6 An alkenyl and / or C _3-6 cycloalkyl group, and the subsequent three groups themselves may be substituted with one or more halo and / or C _1-6 alkyl groups), C _2-6 alkenyl ( _optionally substituted with one or more C _1-6 alkyl groups), C _3-6 cycloalkyl (optionally substituted with one or more halo groups), phenyl (one or more halo groups may be substituted), pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, thiomethyl, methylsulfinyl, methylsulfonyl, = O, -OR ^{^{^{3, -N (R 13) R}}} 14, -C (O) OR 13, -C (O) R 13, -C (O) N (R 13) R 14, -S (O) 2 N (R 13 ) R ¹⁴ and —N (R ¹³ ) S (O) ₂ R ¹⁵ {wherein R ¹³ and R ¹⁴ are independently H, phenyl, C _1-6 alkyl (wherein the alkyl is one or more fluoro atoms) Optionally substituted), C _2-6 alkenyl or C _3-6 cycloalkyl; or R ¹³ and R ¹⁴ are bonded to each other and together with the nitrogen atom to which they are bonded one additional heteroatom And may form a 5- to 7-membered ring which may be substituted with one or more C _1-6 alkyl groups, and the alkyl group itself is substituted with one or more halo groups. even if ^{well; R 15} is _{phenyl, C 1-6} alkyl (which alkyl is one or more fluoro atoms May be conversion), it is selected from C _2-6 optionally substituted alkenyl or C _3-6 cycloalkyl} The compound of claim 38 or 39.

Optional substituents are methyl, ethyl, ethoxy, trifluoromethyl, fluoro, chloro, iodo, phenyl, 2-chlorophenyl, 4-chlorophenyl, n-pentyl, i-propyl, nitro, t-butyl, —CH ₂ CH═ CHC ₈ H _17, trifluoroacetyl, carbomethoxy, is selected from carboethoxy and trifluoromethoxy, a compound according to claim 40.

R ¹ is phenyl, 2-chlorophenyl, 2-chloro-4-fluorophenyl, 3-chloro-4-fluorophenyl, 2,6-dichlorophenyl, 5-chloro-2-cyanophenyl, 2-fluoro-5-trifluoro Methylphenyl, 2-bromo-4-trifluoromethoxyphenyl, 2-methoxy-6-methylphenyl, 3-cyanophenyl, 4-trifluoromethylphenyl, 4-dimethylaminophenyl, 4-carbomethoxyphenyl, 1,3 , 5-Trimethyl-1H-pyrazol-4-yl, 3-methylisoxazol-5-yl, 3-pyridinyl, 2-chloro-3-pyridinyl, 3-methyl-2-pyridinyl, 3-carbomethoxythiophene-2 -Yl or 1,3-benzodioxolyl;
R ² is hydrogen or methyl;
R ³ is methyl, n-butyl, n-pentyl, 1-octyl, oleoyl, (1R, 2S, 5R)-(−)-menthyl, 2-chlorobenzyl, benzyl, phenyl, 3-fluorophenyl, 3- Chlorophenyl, 4-chlorophenyl, 2-fluoro-5-iodophenyl, 5-fluoro-2-methylphenyl, 4-tert-butylphenyl, 4-pentylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-nitrophenyl, 2-ethoxyphenyl, 1-naphthyl, 2-furanyl, 2,5-dimethyl-3-furanyl, 2-carbomethoxy-5-furanyl, 1-methyl-1H-pyrrol-2-yl, 3 -Methyl-2-benzofuranyl, 3-methyl-2-thiophenyl, 1 (N) -methyl-4-piperazinyl, 1 (N)-(2,2,2-trifluoroacetyl) piperidin-4-yl, ethylhexa No art or , It is a 3-benzodioxolyl;
Y is —C (O) —, —C (S) — or —S (O) ₂ —;
42. The compound according to any one of claims 1 or 32 to 41, wherein X is a bond, -N (H)-, -N (Me)-, or -O-.

43. A compound of formula I or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 42, for use as a medicament, excluding the proviso.

However compounds of formula I according to any one of claims 1 excluding the teeth writing 42 or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier A pharmaceutical composition for the treatment of diseases in which inhibition of lipoxygenase activity is desired and / or required .

45. The composition of claim 44 , wherein the lipoxygenase is 15-lipoxygenase.

46. A composition according to claim 44 or 45 , wherein the disease is inflammation and / or has an inflammatory component.

Inflammatory disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, allergic disease, rhinitis, inflammatory bowel disease, ulcer, inflammatory pain, fever, atherosclerosis, coronary artery disease, vasculitis , Pancreatitis, arthritis, osteoarthritis, rheumatoid arthritis, conjunctivitis, iritis, scleritis, uveitis, wound, dermatitis, eczema, psoriasis, stroke, diabetes, autoimmune disease, Alzheimer's disease, multiple sclerosis, 47. The composition of claim 46 , wherein the composition is sarcoidosis, Hodgkin's disease or other malignancy.

43. A medicament for the treatment of diseases in which inhibition of lipoxygenase activity is desired and / or required, comprising: (A) a compound of formula I according to any one of claims 1 to 42, excluding the proviso ; and (B) it viewed including the other therapeutic agent useful in the treatment of inflammation, are each mixed with a pharmaceutically acceptable adjuvant, diluent or carrier formulation of components (a) and (B) Medicine .

43. A pharmaceutical comprising a compound of formula I according to any one of claims 1-42 excluding proviso, other therapeutic agents useful for the treatment of inflammation, and a pharmaceutically acceptable adjuvant, diluent or carrier. 49. The medicament of claim 48 , comprising a formulation.

(A) a pharmaceutical formulation comprising a compound of formula I according to any one of claims 1 to 42 excluding proviso in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier; and (b) A kit of parts comprising components of a pharmaceutical formulation comprising other therapeutic agents useful in the treatment of inflammation in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier, comprising components (a) and (b) 49. The medicament of claim 48 , wherein each is provided in a form suitable for administration in combination with the other.

It is a manufacturing method of the compound of Claim 1, Comprising:
(I) When Y is —S (O) ₂ —, X represents a direct bond or —N (R ⁴ ) —, where R ⁴ represents B ⁴ for compounds of formula I II

A compound of formula III wherein R ¹ and R ² are as defined in claim 1
R ³ -X ^a -Y-L ¹ III
(In the above formula, when Y represents —S (O) ₂ —, or to all other groups of Y, when representing X according to claim 1, X ^a is a direct bond or —N ( B ⁴ ) —, wherein R ³ and Y are as defined in claim 1 and L ¹ represents a suitable leaving group)
(Ii) For compounds of formula I wherein X represents a single bond and Y represents —C (O) —, the compound of formula II
R ³ C (O) OH IV
Reaction with a compound of formula (wherein R ³ is as defined in claim 1);
(Iii) For compounds of formula I wherein X represents a direct bond and Y represents a —C (O) — or —C (S) — group, the compound of formula II above, of formula V
R ³ = Y ^a V
(Wherein Y ^a represents —C (O) — or —C (S) — and R ³ is as defined in claim 1);
(Iv) For compounds of formula I wherein X represents —NH— and Y represents —C (O) — or —C (S) —, a compound of formula II
R ³ N = Y ^a VI
Reaction with a compound of the formula (wherein R ³ is as defined in claim 1 and Y ^a is as defined above);
(V) For compounds of formula I wherein Y represents —C (O) — or —C (S) —,
(A) Formula VII
Cl-Y ^a -Cl VII
A compound of
(B) Formula VIII

A compound of (wherein Y ^a is as described above); or (c) when Y represents —C (O) —, after reaction with triphosgene:
(1) For compounds of formula I wherein X represents a direct bond,
R ³ M IX
Reaction of the compound with (wherein M represents a metal such as Mn, Fe, Ni, Cu, Zn, Pd or Ce, or a salt or complex thereof, and R ³ is as defined in claim 1);
(2) For compounds of formula I where X represents O,
R ³ OH X
Reaction with a compound of formula (wherein R ³ is as defined in claim 1);
(3) For compounds of formula I wherein X represents —N (R ⁴ ) —
R ³ N (H) R ⁴ XI
Reaction with the compound (wherein R ³ and R ⁴ are as defined in claim 1);
(Vi) For compounds of formula I where X represents —N (R ⁴ ) — and R ⁴ is other than hydrogen,
R ⁴ -L ¹ XII
Reaction of a corresponding compound of formula I wherein X represents —N (H) — with a compound of the formula (wherein R ⁴ is as defined in claim 1 and L ¹ is as defined above);
(Vii) For compounds of formula I in which Y represents —C (S) —, conversion of the corresponding compounds of formula I in which Y represents —C (O) — into a thiocarbonyl group Reaction with suitable reagents for;
(Viii) Formula XIII

(Wherein R ³ , Y and X are as defined in claim 1)
Formula XIV
HN (R ¹ ) (R ² ) XIV
Reaction with the compound (wherein R ¹ and R ² are as defined in claim 1);
(Ix) Formula XV

(Wherein R ² , R ³ , Y and X are as defined in claim 1),
Formula XVI
R ¹ -L ² XVI
Wherein L ² is a suitable leaving group and R ¹ is as described in claim 1.