NO310618B1 - Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser - Google Patents

Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser Download PDF

Info

Publication number: NO310618B1
Authority: NO; Norway
Prior art keywords: azabicyclo; imino; heptane; trans; methyl
Prior art date: 1997-04-10

Application number

NO19981658A

Other languages

English (en)

Norwegian (no)

Other versions

NO981658L (no

NO981658D0 (no

Inventor

Naoyuki Taniguchi

Kaoru Kobayashi

Masao Naka

Original Assignee

Ono Pharmaceutical Co

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.)

1997-04-10

Filing date

1998-04-08

Publication date

2001-07-30

1998-04-08 Application filed by Ono Pharmaceutical Co filed Critical Ono Pharmaceutical Co

1998-04-08 Publication of NO981658D0 publication Critical patent/NO981658D0/no

1998-10-12 Publication of NO981658L publication Critical patent/NO981658L/no

2001-07-30 Publication of NO310618B1 publication Critical patent/NO310618B1/no

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 80
238000002360 preparation method Methods 0.000 title claims description 46
150000003053 piperidines Chemical class 0.000 title description 2
238000004519 manufacturing process Methods 0.000 claims abstract description 42
150000003839 salts Chemical class 0.000 claims abstract description 21
239000004480 active ingredient Substances 0.000 claims abstract description 9
239000002253 acid Substances 0.000 claims abstract description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
-1 piperidine compound Chemical class 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 17
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 12
231100000252 nontoxic Toxicity 0.000 claims description 12
230000003000 nontoxic effect Effects 0.000 claims description 12
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QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 8
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239000003765 sweetening agent Substances 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
LHHPEAQVCCPLBC-UHFFFAOYSA-N tributyltin;hydrate Chemical compound O.CCCC[Sn](CCCC)CCCC LHHPEAQVCCPLBC-UHFFFAOYSA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems

Landscapes

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

NO19981658A 1997-04-10 1998-04-08 Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser NO310618B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP9183097		1997-04-10
JP27319697		1997-10-07

Publications (3)

Publication Number	Publication Date
NO981658D0 NO981658D0 (no)	1998-04-08
NO981658L NO981658L (no)	1998-10-12
NO310618B1 true NO310618B1 (no)	2001-07-30

Family

ID=26433266

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19981658A NO310618B1 (no)	1997-04-10	1998-04-08	Kondenserte piperidinforbindelser, fremstilling og anvendelse derav, samt preparater omfattende slike forbindelser

Country Status (14)

Country	Link
US (2)	US6110930A (de)
EP (1)	EP0870763B1 (de)
KR (1)	KR19980081287A (de)
CN (1)	CN1202486A (de)
AT (1)	ATE210647T1 (de)
AU (1)	AU746048B2 (de)
CA (1)	CA2234571A1 (de)
DE (1)	DE69802858T2 (de)
DK (1)	DK0870763T3 (de)
ES (1)	ES2169886T3 (de)
HU (1)	HUP9800865A3 (de)
NO (1)	NO310618B1 (de)
PT (1)	PT870763E (de)
TW (1)	TW427979B (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2793248B1 (fr) *	1999-05-03	2001-06-29	Adir	Nouveaux derives de 2,3-methano-aminoacides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
AU5246000A (en) *	1999-06-09	2000-12-28	Ono Pharmaceutical Co. Ltd.	Analgesics
FR2794647A1 (fr)	1999-06-11	2000-12-15	Centre Nat Rech Scient	Compositions pharmaceutique comprenant du no ou au moins un compose capable de liberer ou d'induire la formation de no dans les cellules
AU5566700A (en) *	1999-06-22	2001-01-09	Ono Pharmaceutical Co. Ltd.	Process for the preparation of intermediate compounds of drugs
FR2803298A1 (fr) *	1999-12-30	2001-07-06	Adir	Nouvelles urees lineaires ou cycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
RU2002121496A (ru) *	2000-02-10	2004-03-20	Оно Фармасьютикал Ко., Лтд. (Jp)	Средство для лечения синдрома шегрена
AU2001296028A1 (en) *	2000-10-30	2002-05-15	Ono Pharmaceutical Co. Ltd.	Remedies for extraocular inflammatory diseases
WO2003022309A1 (fr) *	2001-09-10	2003-03-20	Ono Pharmaceutical Co., Ltd.	Remedes pour maladies allergiques
JP2006096665A (ja) *	2002-10-29	2006-04-13	Ono Pharmaceut Co Ltd	脊柱管狭窄症治療剤
WO2004101523A1 (en) *	2003-05-17	2004-11-25	Korea Research Institute Of Bioscience And Biotechnology	Novel 2-oxo-heterocyclic compounds and the pharmaceutical compositions comprising the same
KR100594377B1 (ko) *	2003-05-17	2006-06-30	한국생명공학연구원	항염증 활성을 갖는 신규 2-옥소-피페리딘 유도체(ⅰ)화합물, 이의 제조방법 및 이를 포함하는 염증 질환의치료를 위한 조성물
US20090186929A1 (en) *	2003-11-10	2009-07-23	U.S. Department Of Veterans Affairs	Method and agent for inducing apoptosis/cell death in leukemia cells
US20050234026A1 (en) *	2003-11-10	2005-10-20	Weinberg Joe B	Method and agent for inducing apoptosis/cell death in leukemia cells
US7364437B2 (en) *	2005-08-04	2008-04-29	Seagate Technology Llc	Electronic device housing
CN101616736B (zh)	2007-02-19	2013-02-13	帝斯曼知识产权资产管理有限公司	含有铂族金属纳米颗粒的催化剂和生产铂族金属纳米颗粒分散体系的工艺
WO2018035046A1 (en)	2016-08-15	2018-02-22	President And Fellows Of Harvard College	Treating infections using idsd from proteus mirabilis

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR100342275B1 (ko) *	1993-10-21	2002-12-05	지.디. 썰 엘엘씨	산화질소신타제저해제로서유용한아미디노유도체
US5629322A (en) *	1994-11-15	1997-05-13	Merck & Co., Inc.	Cyclic amidine analogs as inhibitors of nitric oxide synthase
AU4149696A (en) *	1994-11-15	1996-06-06	Merck & Co., Inc.	Substituted heterocycles as inhibitors of nitric oxide synthase
JPH11511741A (ja) *	1995-05-10	1999-10-12	ジー．ディー．サールアンドカンパニー	環状アミジン化合物から誘導される酸化窒素シンターゼインヒビター

1998
- 1998-04-08 US US09/056,867 patent/US6110930A/en not_active Expired - Fee Related
- 1998-04-08 NO NO19981658A patent/NO310618B1/no not_active IP Right Cessation
- 1998-04-09 EP EP98106569A patent/EP0870763B1/de not_active Expired - Lifetime
- 1998-04-09 DK DK98106569T patent/DK0870763T3/da active
- 1998-04-09 TW TW087105329A patent/TW427979B/zh active
- 1998-04-09 ES ES98106569T patent/ES2169886T3/es not_active Expired - Lifetime
- 1998-04-09 AU AU60777/98A patent/AU746048B2/en not_active Ceased
- 1998-04-09 PT PT98106569T patent/PT870763E/pt unknown
- 1998-04-09 CA CA002234571A patent/CA2234571A1/en not_active Abandoned
- 1998-04-09 CN CN98108834A patent/CN1202486A/zh active Pending
- 1998-04-09 AT AT98106569T patent/ATE210647T1/de not_active IP Right Cessation
- 1998-04-09 DE DE69802858T patent/DE69802858T2/de not_active Expired - Fee Related
- 1998-04-10 KR KR1019980012758A patent/KR19980081287A/ko not_active Ceased
- 1998-04-10 HU HU9800865A patent/HUP9800865A3/hu unknown
2000
- 2000-03-13 US US09/524,255 patent/US6228866B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
ES2169886T3 (es)	2002-07-16
DE69802858T2 (de)	2002-08-08
PT870763E (pt)	2002-06-28
NO981658L (no)	1998-10-12
CN1202486A (zh)	1998-12-23
US6228866B1 (en)	2001-05-08
EP0870763B1 (de)	2001-12-12
HUP9800865A3 (en)	1999-03-01
AU746048B2 (en)	2002-04-11
EP0870763A1 (de)	1998-10-14
CA2234571A1 (en)	1998-10-10
TW427979B (en)	2001-04-01
ATE210647T1 (de)	2001-12-15
NO981658D0 (no)	1998-04-08
KR19980081287A (ko)	1998-11-25
AU6077798A (en)	1998-10-15
US6110930A (en)	2000-08-29
HU9800865D0 (en)	1998-05-28
HUP9800865A2 (hu)	1999-01-28
DE69802858D1 (de)	2002-01-24
DK0870763T3 (da)	2002-03-11

Legal Events

Date	Code	Title	Description
2003-12-08	MM1K	Lapsed by not paying the annual fees	Free format text: LAPSED IN OCTOBER 2003

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