CA2151507C - Composition pharmaceutique contenant des composes de type bicyclique - Google Patents

Composition pharmaceutique contenant des composes de type bicyclique Download PDF

Info

Publication number: CA2151507C
Authority: CA; Canada
Prior art keywords: alkyl; cis; dihydro; hydrogen; dimethyl
Prior art date: 1992-12-11
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

CA002151507A

Other languages

English (en)

Other versions

CA2151507A1 (fr

Inventor

Wai Ngor Chan

John Morris Evans

Geoffrey Stemp

Neil Upton

Robert Nicholas Willette

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

SmithKline Beecham Ltd

SmithKline Beecham Corp

Original Assignee

SmithKline Beecham Ltd

SmithKline Beecham Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-12-11

Filing date

1993-12-08

Publication date

2006-10-03

1992-12-11 Priority claimed from GB929225858A external-priority patent/GB9225858D0/en

1992-12-11 Priority claimed from GB929225861A external-priority patent/GB9225861D0/en

1992-12-11 Priority claimed from GB929225857A external-priority patent/GB9225857D0/en

1993-12-08 Application filed by SmithKline Beecham Ltd, SmithKline Beecham Corp filed Critical SmithKline Beecham Ltd

1993-12-08 Priority claimed from PCT/GB1993/002513 external-priority patent/WO1994013657A1/fr

1994-06-23 Publication of CA2151507A1 publication Critical patent/CA2151507A1/fr

2006-10-03 Application granted granted Critical

2006-10-03 Publication of CA2151507C publication Critical patent/CA2151507C/fr

2013-12-08 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 8
125000002619 bicyclic group Chemical group 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 91
-1 perfluoro Chemical group 0.000 claims abstract description 67
239000001257 hydrogen Substances 0.000 claims abstract description 50
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
150000003839 salts Chemical class 0.000 claims abstract description 34
125000000217 alkyl group Chemical group 0.000 claims abstract description 32
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
125000004169 (C1-C6) alkyl group Chemical class 0.000 claims abstract description 27
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 19
229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 15
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
239000001301 oxygen Substances 0.000 claims abstract description 15
125000003118 aryl group Chemical group 0.000 claims abstract description 13
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 9
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 8
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 8
150000002431 hydrogen Chemical group 0.000 claims abstract description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
239000005864 Sulphur Substances 0.000 claims abstract description 7
125000001589 carboacyl group Chemical group 0.000 claims abstract description 7
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 7
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Chemical group 0.000 claims abstract description 4
125000004685 alkoxythiocarbonyl group Chemical group 0.000 claims abstract description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 4
125000004691 alkyl thio carbonyl group Chemical group 0.000 claims abstract description 4
125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 4
125000005199 aryl carbonyloxy group Chemical group 0.000 claims abstract description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims abstract description 4
125000005469 ethylenyl group Chemical group 0.000 claims abstract description 4
125000005223 heteroarylcarbonyl group Chemical group 0.000 claims abstract description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 4
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical class C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims abstract description 4
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract description 4
150000003852 triazoles Chemical class 0.000 claims abstract description 4
125000005204 heteroarylcarbonyloxy group Chemical group 0.000 claims abstract description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 11
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 10
125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims abstract 3
125000006552 (C3-C8) cycloalkyl group Chemical class 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 33
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
208000035475 disorder Diseases 0.000 claims description 29
238000011282 treatment Methods 0.000 claims description 21
239000001961 anticonvulsive agent Substances 0.000 claims description 17
239000003814 drug Substances 0.000 claims description 17
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
238000011321 prophylaxis Methods 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
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206010015037 epilepsy Diseases 0.000 claims description 11
206010027599 migraine Diseases 0.000 claims description 11
206010008120 Cerebral ischaemia Diseases 0.000 claims description 9
125000004429 atom Chemical group 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
208000018737 Parkinson disease Diseases 0.000 claims description 8
208000028017 Psychotic disease Diseases 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 3
ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 3
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 3
238000010306 acid treatment Methods 0.000 claims description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
229910004679 ONO2 Inorganic materials 0.000 claims 2
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 2
125000003435 aroyl group Chemical group 0.000 claims 2
125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 claims 2
125000003806 alkyl carbonyl amino group Chemical group 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
241001465754 Metazoa Species 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
230000000694 effects Effects 0.000 description 17
239000000203 mixture Substances 0.000 description 17
241000700159 Rattus Species 0.000 description 16
238000012360 testing method Methods 0.000 description 15
239000003981 vehicle Substances 0.000 description 13
238000001356 surgical procedure Methods 0.000 description 11
210000004129 prosencephalon Anatomy 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
229940079593 drug Drugs 0.000 description 9
230000035939 shock Effects 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
210000001367 artery Anatomy 0.000 description 8
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
208000019901 Anxiety disease Diseases 0.000 description 7
206010010904 Convulsion Diseases 0.000 description 7
208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 7
125000003545 alkoxy group Chemical group 0.000 description 7
230000036506 anxiety Effects 0.000 description 7
230000001537 neural effect Effects 0.000 description 7
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 7
239000000243 solution Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
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235000019441 ethanol Nutrition 0.000 description 5
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208000001286 intracranial vasospasm Diseases 0.000 description 5
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230000008961 swelling Effects 0.000 description 5
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
230000001154 acute effect Effects 0.000 description 4
230000000949 anxiolytic effect Effects 0.000 description 4
229940049706 benzodiazepine Drugs 0.000 description 4
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 4
150000001562 benzopyrans Chemical class 0.000 description 4
229960003920 cocaine Drugs 0.000 description 4
125000005842 heteroatom Chemical group 0.000 description 4
238000001802 infusion Methods 0.000 description 4
229960002715 nicotine Drugs 0.000 description 4
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
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125000001424 substituent group Chemical group 0.000 description 4
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 2
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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 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/68—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with nitrogen atoms directly attached in position 4

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA002151507A 1992-12-11 1993-12-08 Composition pharmaceutique contenant des composes de type bicyclique Expired - Lifetime CA2151507C (fr)

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
GB9225857.3		1992-12-11
GB929225858A GB9225858D0 (en)	1992-12-11	1992-12-11	Novel treatment
GB9225861.5		1992-12-11
GB9225858.1		1992-12-11
GB929225861A GB9225861D0 (en)	1992-12-11	1992-12-11	Novel treatment
GB929225857A GB9225857D0 (en)	1992-12-11	1992-12-11	Novel treatment
PCT/GB1993/002513 WO1994013657A1 (fr)	1992-12-11	1993-12-08	Composition pharmaceutique contenant des composes du type bicyclique

Publications (2)

Publication Number	Publication Date
CA2151507A1 CA2151507A1 (fr)	1994-06-23
CA2151507C true CA2151507C (fr)	2006-10-03

Family

ID=37101722

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002151507A Expired - Lifetime CA2151507C (fr)	1992-12-11	1993-12-08	Composition pharmaceutique contenant des composes de type bicyclique

Country Status (1)

Country	Link
CA (1)	CA2151507C (fr)

1993
- 1993-12-08 CA CA002151507A patent/CA2151507C/fr not_active Expired - Lifetime

Also Published As

Publication number	Publication date
CA2151507A1 (fr)	1994-06-23

Legal Events

Date	Code	Title	Description
2000-01-05	EEER	Examination request
2014-02-10	MKEX	Expiry	Effective date: 20131209

Publication	Publication Date	Title
EP0673374B1 (fr)	2000-03-01	Composition pharmaceutique contenant des composes du type bicyclique
EP0764157B1 (fr)	2002-01-02	Benzopyrannes et leur utilisation en tant qu'agents therapeutiques
AU679475B2 (en)	1997-07-03	Bicyclic compounds with pharmaceutical activity
WO1994013292A1 (fr)	1994-06-23	Activateurs des vannes a potassium utilises en therapie
EP0764159B1 (fr)	2000-08-09	Composes a substitution amide c -4 et leur utilisation en tant qu'agents therapeutiques
EP0764158B1 (fr)	2002-09-18	Benzopyrannes et leur utilisation en tant qu'agents therapeutiques
CA2151507C (fr)	2006-10-03	Composition pharmaceutique contenant des composes de type bicyclique
US20030236410A1 (en)	2003-12-25	Pharmaceutical composition containing bicyclic type compounds
HK1012377B (en)	2000-11-24	Pharmaceutical composition containing bicyclic type compounds
EP0674519A1 (fr)	1995-10-04	Activateurs des vannes a potassium utilises en therapie
AU739678B2 (en)	2001-10-18	Benzopyrans and their use as therapeutic agents