Aniline derivatives or salts thereof and cytokine production inhibitors containing the same

• US 7,132,546 B2
• Filed: 12/21/2001
• Issued: 11/07/2006
• Est. Priority Date: 12/22/2000
• Status: Expired due to Fees

• Current Assignee: Ishihara Sangyo Kaisha Limited
• Original Assignee: Ishihara Sangyo Kaisha Limited
• Inventors: Okada, Takashi, Yamamoto, Kazuhiro, Yuki, Shunji, Kimura, Hirohiko, Kato, Fuminori
• Primary Examiner(s): Morris, Patricia L.
• Application Number:
  US10/451,101
• Publication Number:
  US 20040048891A1
• Time in Patent Office: 1,782 Days
• Field of Search: 546/300, 546/312, 514/312
• US Class Current: 546/300
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 27/16 Otologicals
• 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 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 233/65 : having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
• CPC Class Codes: C07C 233/66 : having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07C 233/75 : with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 233/76 : having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
• CPC Class Codes: C07C 233/80 : with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/56 : having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/64 : having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 245/08 : with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
• CPC Class Codes: C07C 255/57 : containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2602/08 : the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2603/74 : Adamantanes
• CPC Class Codes: C07C 311/21 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/46 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 311/51 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 323/42 : Y being a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 213/40 : Acylated substituent nitrogen atom
• CPC Class Codes: C07D 213/61 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 213/64 : attached in position 2 or 6
• CPC Class Codes: C07D 213/643 : 2-Phenoxypyridines; Derivatives thereof
• CPC Class Codes: C07D 213/70 : Sulfur atoms
• CPC Class Codes: C07D 213/71 : to which a second hetero atom is attached
• CPC Class Codes: C07D 213/74 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 213/76 : to which a second hetero atom is attached nitro radicals C07D213/61
• CPC Class Codes: C07D 239/47 : One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• CPC Class Codes: C07D 241/44 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 277/46 : by carboxylic acids, or sulfur or nitrogen analogues thereof
• CPC Class Codes: C07D 277/52 : to sulfur atoms, e.g. sulfonamides
• CPC Class Codes: C07D 277/62 : Benzothiazoles
• CPC Class Codes: C07D 277/66 : with aromatic rings or ring systems directly attached in position 2
• CPC Class Codes: C07D 277/82 : Nitrogen atoms
• CPC Class Codes: C07D 295/135 : with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides a cytokine production inhibitor containing as an active ingredient an aniline derivative of the formula (I) or a salt thereof:

[wherein A is CO or SO₂; Cy is an aryl group or a heterocyclic group; each of R¹ and R² which are independent of each other, is a halogen atom, a cyano group, a nitro group, an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cycloalkyl group which may be substituted, a cycloalkenyl group which may be substituted, an aryl group which may be substituted, a heterocyclic group which may be substituted, an amino group which may be substituted or a —B-Q group; R³ is a -M¹-M²-R⁵ group; R⁴ is a hydrogen atom or an alkyl group which may be substituted; x is an integer of from 0 to 5; y is an integer of from 0 to 4; and z is an integer of from 0 to 1].

Claims

1. An aniline derivative of the formula (I′

) or a salt thereof, said derivative and salt having cytokine production inhibitor activity;

2. The aniline derivative or a salt thereof according to claim 1, wherein A is CO.

3. The aniline derivative or a salt thereof according to claim 1, wherein A is CO, and R^5′

is a pyridyl group which may be substituted.

4. The aniline derivative or a salt thereof according to claim 1, wherein A is CO, and R^5′

is a pyridyl group substituted with a haloalkyl group (provided that the pyridyl group may be substituted with at least one substituent selected from the group consisting of a halogen atom, a hydroxyl group, a mercapto group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an alkenyloxy group, an alkenylthio group, an alkynyloxy group, an alkynylthio group, cycloalkyl group, a cycloalkenyl group, a cycloalkoxy group, a cycloalkylthio group, a cycloalkenyloxy group, a cycloalkenylthio group, an alkoxycarbonyl group, an alkylcarbonyl group, an alkylcarbonyloxy group, an alkenyloxycarbonyl group, an alkenylcarbonyl group, an alkenylcarbonyloxy group, an alkynyloxycarbonyl group, an alkynylcarbonyl group, an alkynylcarbonyloxy group, a cycloalkoxycarbonyl group, a cycloalkylcarbonyl group, a cycloalkylcarbonyloxy group, a cycloalkenyloxycarbonyl group, a cycloalkenylcarbonyl group, a cycloalkenylcarbonyloxy group, an aryl group, an aryloxy group, an arylthio group, an aryloxycarbonyl group, an arylcarbonyl group, an arylcarbonyloxy group, an amino group, a cyano group, a nitro group, a carboxyl group, an aminocarbonyl group, an alkylsulfonyl group, an alkenylsulfonyl group, an alkynylsulfonyl group, a cycloalkylsulfonyl group, a cycloalkenylsulfonyl group, an arylsulfonyl group, and an aminosulfonyl group).

5. The aniline derivative or a salt thereof according to claim 1, wherein A is CO, and R^5′

is a 3-chloro-5-trifluoromethyl-2-pyridyl group.