JP2000034288A

JP2000034288A - スピロピペリジン誘導体

スピロピペリジン誘導体

Info

Publication number: JP2000034288A
Authority: JP; Japan
Prior art keywords: single bond; place; group; diclph; difph
Prior art date: 1998-01-23
Legal status : Pending

Application number

JP11014058A

Other languages

English (en)

Japanese (ja)

Other versions

JP2000034288A5 (enExample

Inventor

Takehide Nishi

剛秀西

Katsuyoshi Nakajima

勝義中島

Sachiko Iio

幸子飯尾

Takeshi Yamaguchi

武山口

Toshiyasu Takemoto

利泰竹元

Current Assignee

Sankyo Co Ltd

Original Assignee

Sankyo Co Ltd

Priority date

1998-01-23

Filing date

1999-01-22

Publication date

2000-02-02

1999-01-22 Application filed by Sankyo Co Ltd filed Critical Sankyo Co Ltd

1999-01-22 Priority to JP11014058A priority Critical patent/JP2000034288A/ja

2000-02-02 Publication of JP2000034288A publication Critical patent/JP2000034288A/ja

2006-04-06 Publication of JP2000034288A5 publication Critical patent/JP2000034288A5/ja

Status Pending legal-status Critical Current

Links

JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical class C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 title abstract description 7
150000001875 compounds Chemical class 0.000 claims abstract description 118
125000003118 aryl group Chemical group 0.000 claims abstract description 57
125000000217 alkyl group Chemical group 0.000 claims abstract description 50
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 37
125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims abstract description 29
125000002947 alkylene group Chemical group 0.000 claims abstract description 13
229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract 3
-1 3,4,5-trimethoxybenzoyl Chemical group 0.000 claims description 294
125000001424 substituent group Chemical group 0.000 claims description 68
150000002148 esters Chemical class 0.000 claims description 40
150000003839 salts Chemical class 0.000 claims description 39
125000004432 carbon atom Chemical group C* 0.000 claims description 36
125000003003 spiro group Chemical group 0.000 claims description 25
239000003814 drug Substances 0.000 claims description 23
125000004122 cyclic group Chemical group 0.000 claims description 20
125000005843 halogen group Chemical group 0.000 claims description 18
238000000034 method Methods 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 18
125000001072 heteroaryl group Chemical group 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000002252 acyl group Chemical group 0.000 claims description 13
125000001931 aliphatic group Chemical group 0.000 claims description 13
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000004430 oxygen atom Chemical group O* 0.000 claims description 9
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 6
125000004434 sulfur atom Chemical group 0.000 claims description 6
125000004450 alkenylene group Chemical group 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000004043 oxo group Chemical group O=* 0.000 claims description 4
UHKAJLSKXBADFT-UHFFFAOYSA-N 1,3-indandione Chemical compound C1=CC=C2C(=O)CC(=O)C2=C1 UHKAJLSKXBADFT-UHFFFAOYSA-N 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 3
235000014113 dietary fatty acids Nutrition 0.000 claims description 2
239000000194 fatty acid Substances 0.000 claims description 2
229930195729 fatty acid Natural products 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
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239000002904 solvent Substances 0.000 abstract description 29
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108010072901 Tachykinin Receptors Proteins 0.000 abstract description 3
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239000003795 chemical substances by application Substances 0.000 abstract description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
238000011321 prophylaxis Methods 0.000 abstract 1
230000001988 toxicity Effects 0.000 abstract 1
231100000419 toxicity Toxicity 0.000 abstract 1
238000011282 treatment Methods 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
238000006243 chemical reaction Methods 0.000 description 31
238000012360 testing method Methods 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 27
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
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230000037396 body weight Effects 0.000 description 10
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
201000010099 disease Diseases 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000000126 substance Substances 0.000 description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
229910052783 alkali metal Inorganic materials 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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201000004624 Dermatitis Diseases 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
208000019695 Migraine disease Diseases 0.000 description 6
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
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QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 5
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QXNXVWNYCKUANQ-UHFFFAOYSA-N spiro[indene-1,4'-piperidine] Chemical compound C1CNCCC21C1=CC=CC=C1C=C2 QXNXVWNYCKUANQ-UHFFFAOYSA-N 0.000 description 4
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