JP2000502690A - タキキニンレセプターアンタゴニストとしての1−(1,2−ジ置換ピペリジニル)−4−置換ピペリジン誘導体 - Google Patents
タキキニンレセプターアンタゴニストとしての1−(1,2−ジ置換ピペリジニル)−4−置換ピペリジン誘導体Info
- Publication number
- JP2000502690A JP2000502690A JP09524031A JP52403197A JP2000502690A JP 2000502690 A JP2000502690 A JP 2000502690A JP 09524031 A JP09524031 A JP 09524031A JP 52403197 A JP52403197 A JP 52403197A JP 2000502690 A JP2000502690 A JP 2000502690A
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- Prior art keywords
- alkyl
- formula
- phenyl
- hydrogen
- halo
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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- C07—ORGANIC CHEMISTRY
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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
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- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式 上記式中、 nは、0、1または2であり、 mは、1または2であり、ただしmが2である場合、nは1であり、 pは、0、1または2であり、 =Qは、=Oまたは=NR3であり、 Xは、共有結合または式−O−、−S−、−NR3−の二価の基であり、 R1は、Ar1、Ar1C1-6アルキルまたはジ(Ar1)C1-6アルキルであり、場 合によっては、各C1-6アルキル基がヒドロキシ、C1-4アルキルオキシ、オキソ または式−O−CH2−CH2−O−もしくは−O−CH2−CH2−CH2−O− のケタール化オキソ置換基で置換され、 R2は、Ar2、Ar2C1-6アルキル、HetまたはHetC1-6アルキルであり 、 R3は、水素またはC1-6アルキルであり、 R4は、水素、C1-4アルキル、C1-4アルキルオキシC1-4アルキル、ヒドロキシ C1-4アルキル、カルボキシル、C1-4アルキルオキシカルボニルまたはAr3で あり、 R5は、水素;ヒドロキシ;Ar3;Ar3C1-6アルキルオキシ;ジ(Ar3)C1 -6 アルキルオキシ;Ar3C1-6アルキルチオ;ジ(A r3)C1-6アルキルチオ;Ar3C1-6アルキルスルホキシ;ジ(Ar3)C1-6ア ルキルスルホキシ;Ar3C1-6アルキルスルホニル;ジ(Ar3)C1-6アルキル スルホニル;−NR7R8;−NR7R8で置換されたC1-6アルキル;または式の基であり、 上記式中、R7は、水素、C1-6アルキル、ピリジニルまたはAr3であり、 R8は、水素;C1-6アルキル;Ar3C1-6アルキル;ジ(Ar3)C1-6アルキル ;Ar3、C1-6アルキルもしくはAr3C1-6アルキルで置換されたイミダゾリル ;ベンゾオキサゾリルまたはベンゾチアゾリルであり、 R9は、水素;ヒドロキシ;C1-6アルキル;C1-6アルキルオキシ;Ar3;Ar3 C1-6アルキル;ジ(Ar3)C1-6アルキル;アミノ;モノ−もしくはジ(C1- 6 アルキル)アミノ;イミダゾリル:Ar3、C1-6アルキルもしくはAr3C1-6 アルキルで置換されたイミダゾリル;ピロリジニル;ピペリジニル;ホモピペリ ジニル;モルホリニルまたはチオモルホリニルであり、 R10は、水素またはC1-6アルキルカルボニルであり、 R11は、水素;ハロまたはモノ−、ジ−もしくはトリ(ハロ)メチルであり、 Yは、Y1またはY2であり、この場合、 Y1は、共有結合、C1-6アルカンジイル、−NR7もしくは−C1-6アルカ ンジイル−NR7−であり、または Y2は、R9がヒドロキシもしくはC1-6アルキルオキシ以外である場合、 −O−であり、 R4及びR5は一緒に、式−O−CH2−CH2−O−または−C(=O)−NR3 −CH2−NR7−の2価の基を形成してもよく、 R6は、水素、ヒドロキシ、C1-6アルキルオキシ、C1-6アルキルまたはAr3C1-6 アルキルであり、 Ar1は、フェニル;ハロ、C1-4アルキル、ハロC1-4アルキル、シアノ、アミ ノカルボニル、C1-4アルキルオキシもしくはハロC1-4アルキルオキシから各々 独立して選択された1、2もしくは3個の置換基で置換されたフェニルであり、 Ar2は、ナフタレニル;フェニル;ヒドロキシ、ハロ、シアノ、ニトロ、アミ ノ、モノ−もしくはジ(C1-4アルキル)アミノ、C1-4アルキル、ハロC1-4ア ルキル、C1-4アルキルオキシ、ハロC1-4アルキルオキシ、カルボキシル、C1- 4 アルキルオキシカルボニル、アミノカルボニル及びモノ−もしくはジ(C1-4ア ルキル)アミノカルボニルから各々独立して選択された1、2もしくは3個の置 換基で置換されたフェニルであり、 Ar3は、フェニルまたはハロ、ヒドロキシ、アミノ、ニトロ、アミノカルボニ ル、C1-6アルキル、ハロC1-6アルキルもしくはC1-6 アルキルオキシから選択された1、2もしくは3個の置換基で置換されたフェニ ルであり、そして Hetは、ピロリル、ピラゾリル、イミダゾリル、フラニル、チエニル、オキサ ゾリル、イソオキサゾリル、チアゾリル、イソチアゾリル、ピリジニル、ピリミ ジニル、ピラジニル及びピリダジニルから選択された単環式複素環またはキノリ ニル、キノキサリニル、インドリル、ベンゾイミダゾリル、ベンゾオキサゾリル 、ベンゾイソオキサゾリル、ベンゾチアゾリル、ベンゾイソチアゾリル、ベンゾ フラニル及びベンゾチエニルから選択された二環式複素環であり、場合によって は、各単環式及び二環式複素環が、炭素原子においてハロ、C1-4アルキルまた はモノ−、ジ−もしくはトリ(ハロ)メチルから選択された1または2個の置換 基で置換されていてもよい、 の化合物、N−オキシド形、製薬学的に受容しうる付加塩またはその立体化学的 異性体。 2. R8が、水素、C1-6アルキル、Ar3C1-6アルキル、ジ(Ar3)C1-6 アルキル、ベンゾオキサゾリルまたはベンゾチアゾリルであり、R9が、水素、 ヒドロキシ、C1-6アルキル、C1-6アルキルオキシ、Ar3、Ar3C1-6アルキ ル、ジ(Ar3)C1-6アルキル、アミノ、モノ−もしくはジ(C1-6アルキル) アミノ、ピロリジニル、ピペリジニル、ホモ−ピペリジニル、モルホリニルまた はチオモルホリニルであり、そしてHetが、ピロリル、ピラゾリル、イミダゾ リル、フラニル、チエニル、オキサゾリル、イソオキサゾリル、チアゾリル、イ ソチアゾリル、ピリジニル、ピリミジニル、ピラジニル及びピリダジニルから選 択され た単環式複素環またはキノリニル、ベンゾイミダゾリル、ベンゾオキサゾリル、 ベンゾイソオキサゾリル、ベンゾチアゾリル、ベンゾイソチアゾリル、ベンゾフ ラニル及びベンゾチエニルから選択された二環式複素環であり、場合によっては 、各単環式及び二環式複素環が、炭素原子においてハロ、C1-4アルキルまたは モノ−、ジ−もしくはトリ(ハロ)メチルから選択された1もしくは2個の置換 基で置換されていてもよい、請求の範囲1に請求された化合物。 3. R1がAr1C1-6アルキルであり、R2が、メチルまたはトリフルオロメ チルから選択された2置換基で置換されたフェニルであり、Xが共有結合であり 、そして=Qが=Oである請求の範囲1または2に請求された化合物。 4. m、n及びpが1である請求の範囲1ないし3のいずれかに請求された 化合物。 5. pが1であり、R4が水素;C1-4アルキルオキシC1-4アルキル;フェ ニル;またはハロで置換されたフェニルであり、R5がフェニル;フェニルもし くは置換されたイミダゾリルで置換されたアミノ;またはハロで置換されたフェ ニルであり、あるいはR5が式(a−1)の基であり、この式中、YがY1または Y2であり、この場合、Y1が共有結合、−NR7または−CH2−NR7−であり 、ここでR7が水素または場合によってはハロで置換されたフェニルであり、Y2 が−O−であり、R9がC1-6アルキル、C1-6アルキルオキシ、ピロリジニル、 フェニルC1-6アルキル、フェニルC1-6アルキルで置換されたイミダゾリルまた はAr3であり、あるいはR5が式(a−2)の基であり、この式中、R10が水素 またはC1-6アルキルカルボニルであり、R11が水素であり、 あるいはR4及びR5が一緒に、式−C(=O)−NR3−CH2−NR7−の2価 の基を形成し、この式中、各R7が独立して水素またはフェニルから選択され、 そしてR6が水素である請求の範囲1ないし4のいずれかに請求された化合物。 6. 化合物が、 1−[3,5−ビス(トリフルオロメチル)ベンゾイル]−4−[4−(2,3 −ジヒドロ−2−オキソ−1H−ベンゾイミダゾール−1−イル)−1−ピペリ ジニル]−2−(フェニルメチル)ピペリジン、 1−[3,5−ビス(トリフルオロメチル)ベンゾイル]−2−(フェニルメチ ル)−4−[4−フェニル−4−(1−ピロリジニルカルボニル)−1−ピペリ ジニル]ピペリジン、 N−[[1−[1−[3,5−ビス(トリフルオロメチル)ベンゾイル]−2− (フェニルメチル)−4−ピペリジニル]−4−フェニル−4−ピペリジニル] メチル]アセトアミド、または 1−[3,5−ビス(トリフルオロメチル)ベンゾイル]−4−[4−オキソ− 1−フェニル−1,3,8−トリアザスピロ[4.5]デク(dec)−8−イ ル]−2−(フェニルメチル)ピペリジン、 1−[3,5−ビス(トリフルオロメチル)ベンゾイル]−4−[4−フェニル −4−(1−ピロリジニルカルボニル)−1−ピペリジニル]−2−[[4−( トリフルオロメチル)フェニル]メチル]ピペリジン、及び 1−[3,5−ビス(トリフルオロメチル)ベンゾイル]−2−[(3,4−ジ フルオロフェニル)メチル]−4−[4−フェニル−4−(1−ピロリジニルカ ルボニル)−1−ピペリジニル]ピペリジン、立体異性 体またはその製薬学的に受容しうる酸付加塩である請求の範囲1に請求された化 合物。 7. 医薬品としての使用のための請求の範囲1ないし6のいずれかに請求さ れた化合物。 8. 製薬学的に受容しうる担体及び有効成分として治療的に有効量の請求の 範囲1ないし6のいずれかに請求された化合物を含んでなる製薬学的組成物。 9. 製薬学的に受容しうる担体を治療的に有効量の請求の範囲1ないし6の いずれかに請求された化合物とよく混合することを特徴とする、請求の範囲8に 請求された組成物の製造方法。 10. a)反応不活性溶媒中、還元剤の存在下で、そして場合によっては適 当な触媒の存在下で、R4、R5及びR6が請求の範囲1に定義したとおりである 式(III)の中間体をR1、R2、X、=Q、n、m及びpが請求の範囲1に定義 したとおりである式(II)の中間体と還元的にN−アルキル化し、 b)反応不活性溶媒中、適当な塩基の存在下で、R2、X及び=Qが請求の範囲 1に定義したとおりであり、そしてW1が適当な脱離基である式(IV)の中間体 をR1、R4、R5、R6、X、=Q、n、m及びpが請求の範囲1に定義したとお りである式(V)の中間体と反応させ、 c)R1、R2、R6、X、=Q、n、m及びpが請求の範囲1に定義したとおり である式(VI)のピペリジノン誘導体をMが適当な有機金属部分であり、そして R4’が請求の範囲1に定義したR4と同じであるが水素以外である式(VII)の 中間体と反応させ、 そして、適切な場合、当該技術分野で知られている転化により式(I)の化合物 を互いに転化し、そしてさらに、適切な場合、酸との処理により式(I)の化合 物を治療に有効な無毒の酸付加塩に転化し、または逆に、アルカリとの処理によ り酸付加塩形態を遊離塩基に転化し、そして適切な場合、これらの立体化学的異 性体もしくはN−オキシド形を製造することを特徴とする請求の範囲1に請求さ れた化合物の製造方法。
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NZ321575A (en) | 1995-10-30 | 1999-05-28 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4- substituted piperazine derivatives |
TW531537B (en) | 1995-12-27 | 2003-05-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-substituted piperidine derivatives |
TW429256B (en) * | 1995-12-27 | 2001-04-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-(benzimidazolyl- and imidazopyridinyl)-piperidine derivatives |
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JP2005532361A (ja) * | 2002-06-17 | 2005-10-27 | メルク エンド カムパニー インコーポレーテッド | 高眼圧症の治療用の眼科用組成物 |
JP2006512348A (ja) * | 2002-12-23 | 2006-04-13 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 置換1−ピペリジン−3−イル−4−ピペリジン−4−イル−ピペラジン誘導体およびそれらのニューロキニン拮抗薬としての使用 |
JP4660198B2 (ja) * | 2002-12-23 | 2011-03-30 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 置換1−ピペリジン−3−イル−4−ピペリジン−4−イル−ピペラジン誘導体およびそれらのニューロキニン拮抗薬としての使用 |
WO2006054513A1 (ja) * | 2004-11-19 | 2006-05-26 | Kissei Pharmaceutical Co., Ltd. | 神経因性疼痛の予防又は治療剤 |
JPWO2006054513A1 (ja) * | 2004-11-19 | 2008-05-29 | キッセイ薬品工業株式会社 | 神経因性疼痛の予防又は治療剤 |
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