JP2006519208A - 新規ジアザビシクロアリール誘導体 - Google Patents
新規ジアザビシクロアリール誘導体 Download PDFInfo
- Publication number
- JP2006519208A JP2006519208A JP2006502001A JP2006502001A JP2006519208A JP 2006519208 A JP2006519208 A JP 2006519208A JP 2006502001 A JP2006502001 A JP 2006502001A JP 2006502001 A JP2006502001 A JP 2006502001A JP 2006519208 A JP2006519208 A JP 2006519208A
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- Prior art keywords
- phenyl
- alkyl
- diaza
- bicyclo
- furan
- Prior art date
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- Ceased
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- 125000000217 alkyl group Chemical group 0.000 claims description 106
- 238000000034 method Methods 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 239000001257 hydrogen Substances 0.000 claims description 77
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 46
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 38
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 37
- 125000004104 aryloxy group Chemical group 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 31
- 125000001475 halogen functional group Chemical group 0.000 claims description 31
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 29
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- BJLUNDZICFZBJD-UHFFFAOYSA-N [5-(4-aminophenyl)furan-2-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone Chemical compound C1=CC(N)=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 BJLUNDZICFZBJD-UHFFFAOYSA-N 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
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- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
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- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 6
- 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 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 6
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- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 6
- 229940047889 isobutyramide Drugs 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- XNMFNLRNMZWUIA-UHFFFAOYSA-N n-[4-[5-(1,4-diazabicyclo[3.2.2]nonane-4-carbonyl)furan-2-yl]phenyl]prop-2-enamide Chemical compound C1=CC(NC(=O)C=C)=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 XNMFNLRNMZWUIA-UHFFFAOYSA-N 0.000 claims description 6
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
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- KZTBGMWRHBBBPK-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(2-phenylethynyl)furan-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C#CC1=CC=CC=C1 KZTBGMWRHBBBPK-UHFFFAOYSA-N 0.000 claims description 4
- GQIFXRMBIAUXKQ-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(3,5-dichlorophenoxy)furan-2-yl]methanone Chemical compound ClC1=CC(Cl)=CC(OC=2OC(=CC=2)C(=O)N2C3CCN(CC3)CC2)=C1 GQIFXRMBIAUXKQ-UHFFFAOYSA-N 0.000 claims description 4
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
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- 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 claims description 4
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- QZGHAGYWPNKMDA-UHFFFAOYSA-N n-[4-[5-(1,4-diazabicyclo[3.2.2]nonane-4-carbonyl)furan-2-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 QZGHAGYWPNKMDA-UHFFFAOYSA-N 0.000 claims description 4
- YBBICDNRBJYUCE-UHFFFAOYSA-N n-[4-[5-(1,4-diazabicyclo[3.2.2]nonane-4-carbonyl)furan-2-yl]phenyl]formamide Chemical compound C1=CC(NC=O)=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 YBBICDNRBJYUCE-UHFFFAOYSA-N 0.000 claims description 4
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- UFSFIYCYNOTBHE-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(2-nitrophenyl)furan-2-yl]methanone Chemical compound [O-][N+](=O)C1=CC=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 UFSFIYCYNOTBHE-UHFFFAOYSA-N 0.000 claims description 3
- XGPOLGZOWNUHAQ-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(3-nitrophenyl)furan-2-yl]methanone Chemical compound [O-][N+](=O)C1=CC=CC(C=2OC(=CC=2)C(=O)N2C3CCN(CC3)CC2)=C1 XGPOLGZOWNUHAQ-UHFFFAOYSA-N 0.000 claims description 3
- RSNBYPOHHFTGQR-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(4-methyl-2-nitrophenyl)furan-2-yl]methanone Chemical compound [O-][N+](=O)C1=CC(C)=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 RSNBYPOHHFTGQR-UHFFFAOYSA-N 0.000 claims description 3
- PQJGRVDZIMMNNW-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(4-nitrophenyl)furan-2-yl]methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 PQJGRVDZIMMNNW-UHFFFAOYSA-N 0.000 claims description 3
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- QELUQQRTYJZTSY-UHFFFAOYSA-N [5-(2-aminophenyl)furan-2-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone Chemical compound NC1=CC=CC=C1C1=CC=C(C(=O)N2C3CCN(CC3)CC2)O1 QELUQQRTYJZTSY-UHFFFAOYSA-N 0.000 claims description 3
- JCNNFDOJIGHJCS-UHFFFAOYSA-N [5-(3-aminophenyl)furan-2-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone Chemical compound NC1=CC=CC(C=2OC(=CC=2)C(=O)N2C3CCN(CC3)CC2)=C1 JCNNFDOJIGHJCS-UHFFFAOYSA-N 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- LYTCVQQGCSNFJU-LKGYBJPKSA-N α-bungarotoxin Chemical compound C(/[C@H]1O[C@H]2C[C@H]3O[C@@H](CC(=C)C=O)C[C@H](O)[C@]3(C)O[C@@H]2C[C@@H]1O[C@@H]1C2)=C/C[C@]1(C)O[C@H]1[C@@]2(C)O[C@]2(C)CC[C@@H]3O[C@@H]4C[C@]5(C)O[C@@H]6C(C)=CC(=O)O[C@H]6C[C@H]5O[C@H]4C[C@@H](C)[C@H]3O[C@H]2C1 LYTCVQQGCSNFJU-LKGYBJPKSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
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- Addiction (AREA)
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- Pain & Pain Management (AREA)
- Reproductive Health (AREA)
- Orthopedic Medicine & Surgery (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Child & Adolescent Psychology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Urology & Nephrology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44987103P | 2003-02-27 | 2003-02-27 | |
| DKPA200300310 | 2003-02-27 | ||
| DKPA200300940 | 2003-06-24 | ||
| US48202203P | 2003-06-25 | 2003-06-25 | |
| PCT/EP2004/050079 WO2004076453A1 (en) | 2003-02-27 | 2004-02-04 | Novel diazabicyclic aryl derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006519208A true JP2006519208A (ja) | 2006-08-24 |
| JP2006519208A5 JP2006519208A5 (enExample) | 2010-10-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006502001A Ceased JP2006519208A (ja) | 2003-02-27 | 2004-02-04 | 新規ジアザビシクロアリール誘導体 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7678788B2 (enExample) |
| EP (1) | EP1599476B1 (enExample) |
| JP (1) | JP2006519208A (enExample) |
| AT (1) | ATE445618T1 (enExample) |
| AU (1) | AU2004215658B2 (enExample) |
| BR (1) | BRPI0407216A (enExample) |
| CA (1) | CA2518675A1 (enExample) |
| DE (1) | DE602004023586D1 (enExample) |
| MX (1) | MXPA05006861A (enExample) |
| NZ (1) | NZ540998A (enExample) |
| WO (1) | WO2004076453A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007520527A (ja) * | 2004-02-04 | 2007-07-26 | ノイロサーチ アクティーゼルスカブ | ニコチン性アセチルコリン受容体リガンドとしてのジアザ２環式アリール誘導体 |
| JP2010509230A (ja) * | 2006-11-02 | 2010-03-25 | ターガセプト，インコーポレイテッド | ニコチン性アセチルコリン受容体サブタイプ選択的なジアザビシクロアルカンのアミド |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0202430D0 (sv) * | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | New Compounds |
| SE0202465D0 (sv) * | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | New compounds |
| US7094572B2 (en) | 2003-03-14 | 2006-08-22 | Bristol-Myers Squibb | Polynucleotide encoding a novel human G-protein coupled receptor variant of HM74, HGPRBMY74 |
| TW200529860A (en) * | 2003-12-22 | 2005-09-16 | Astrazeneca Ab | Nicotinic acetylcholine receptor ligands |
| EP1713809B1 (en) * | 2004-02-04 | 2009-07-29 | Neurosearch A/S | Dimeric azacyclic compounds and their use |
| KR20070015607A (ko) | 2004-05-07 | 2007-02-05 | 메모리 파마슈티칼스 코포레이션 | 1ｈ-인다졸, 벤조티아졸, 1,2-벤조이속사졸,1,2-벤조이소티아졸, 및 크로몬 및 그의 제조법 및 용도 |
| EP1751150A2 (en) | 2004-05-19 | 2007-02-14 | Neurosearch A/S | Novel azabicyclic aryl derivatives |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| GB0723814D0 (en) * | 2007-12-05 | 2008-01-16 | Glaxo Group Ltd | Compounds |
| DE102008015032A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte Pyrazolamide und ihre Verwendung |
| DE102008015033A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte (Pyrazolyl-carbonyl)imidazolidinone und ihre Verwendung |
| DE102008062878A1 (de) | 2008-12-17 | 2010-06-24 | Aicuris Gmbh & Co. Kg | Substituierte Furancarboxamide und ihre Verwendung |
| DE102008062863A1 (de) | 2008-12-17 | 2010-06-24 | Aicuris Gmbh & Co. Kg | Substituierte (Thiophenyl-carbonyl)imidazolidinone und ihre Verwendung |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| TWI558398B (zh) | 2009-09-22 | 2016-11-21 | 諾華公司 | 菸鹼乙醯膽鹼受體α７活化劑之用途 |
| CA2822357A1 (en) | 2010-12-22 | 2012-06-28 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001092261A1 (fr) * | 2000-05-31 | 2001-12-06 | Sanofi-Synthelabo | Derives de 1,4-diazabicyclo [3.2.2]nonanebenzoxazole, -benzothiazole et -benzimidazole, leur preparation et leur application therapeutique |
| WO2001092259A1 (fr) * | 2000-05-31 | 2001-12-06 | Sanofi-Synthelabo | Derives de 1,4-diazabicyclo[3.22]nonane-phenylisoxazole, leur preparation et leur application en therapeutique |
| JP2002255965A (ja) * | 2000-12-29 | 2002-09-11 | Pfizer Prod Inc | Ｃｎｓおよび他の疾患のための医薬組成物 |
| JP2002302490A (ja) * | 2001-02-06 | 2002-10-18 | Pfizer Prod Inc | Ｃｎｓ障害及び他の障害治療用医薬組成物 |
| JP2002540208A (ja) * | 1999-03-30 | 2002-11-26 | サノフィ−サンテラボ | １，４−ジアザビシクロ［３．２．２］ノナン−４−カルボキシレートおよびカルボキサミド誘導体、治療におけるその製造ならびに使用 |
| JP2005507241A (ja) * | 2001-06-11 | 2005-03-17 | メディカル リサーチ カウンシル | 多様性の生成方法 |
| JP2005539030A (ja) * | 2002-08-14 | 2005-12-22 | アストラゼネカ・アクチエボラーグ | ニコチン性アセチルコリン作用剤としてのアリール置換ジアザビシクロアルカン |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60008866T2 (de) * | 1999-05-04 | 2005-01-27 | Neurosearch A/S | Heteroaryl diazabicycloalkene, deren herstellung und verwendung |
| FR2804430B1 (fr) * | 2000-01-28 | 2002-03-22 | Sanofi Synthelabo | Derives de 4-heteroaryl-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
| FR2832713B1 (fr) | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(1,3,4-thiadiazol-2-yl)-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
| FR2832712B1 (fr) | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(oxadiazol-3-yl)-1,4-diazabicyclo[3.2.2]nonane, leur preparation et leur application en therapeutique |
| US20050227699A1 (en) | 2002-06-26 | 2005-10-13 | Harmen Schreuder | Method and network element for optimisation of radio resource utilisation in radio access network |
| SE0202430D0 (sv) * | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | New Compounds |
| DE60326894D1 (de) | 2002-09-30 | 2009-05-07 | Neurosearch As | 1,4-Diazabicycloalkanderivate, deren Herstellung und Verwendung |
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2004
- 2004-02-04 NZ NZ540998A patent/NZ540998A/en not_active IP Right Cessation
- 2004-02-04 BR BR0407216-2A patent/BRPI0407216A/pt not_active Application Discontinuation
- 2004-02-04 AU AU2004215658A patent/AU2004215658B2/en not_active Ceased
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- 2004-02-04 MX MXPA05006861A patent/MXPA05006861A/es active IP Right Grant
- 2004-02-04 CA CA002518675A patent/CA2518675A1/en not_active Abandoned
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- 2004-02-04 DE DE602004023586T patent/DE602004023586D1/de not_active Expired - Lifetime
- 2004-02-04 EP EP04707948A patent/EP1599476B1/en not_active Expired - Lifetime
- 2004-02-04 AT AT04707948T patent/ATE445618T1/de not_active IP Right Cessation
- 2004-02-04 JP JP2006502001A patent/JP2006519208A/ja not_active Ceased
-
2010
- 2010-01-27 US US12/694,952 patent/US20100130483A1/en not_active Abandoned
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002540208A (ja) * | 1999-03-30 | 2002-11-26 | サノフィ−サンテラボ | １，４−ジアザビシクロ［３．２．２］ノナン−４−カルボキシレートおよびカルボキサミド誘導体、治療におけるその製造ならびに使用 |
| WO2001092261A1 (fr) * | 2000-05-31 | 2001-12-06 | Sanofi-Synthelabo | Derives de 1,4-diazabicyclo [3.2.2]nonanebenzoxazole, -benzothiazole et -benzimidazole, leur preparation et leur application therapeutique |
| WO2001092259A1 (fr) * | 2000-05-31 | 2001-12-06 | Sanofi-Synthelabo | Derives de 1,4-diazabicyclo[3.22]nonane-phenylisoxazole, leur preparation et leur application en therapeutique |
| JP2002255965A (ja) * | 2000-12-29 | 2002-09-11 | Pfizer Prod Inc | Ｃｎｓおよび他の疾患のための医薬組成物 |
| JP2002302490A (ja) * | 2001-02-06 | 2002-10-18 | Pfizer Prod Inc | Ｃｎｓ障害及び他の障害治療用医薬組成物 |
| JP2005507241A (ja) * | 2001-06-11 | 2005-03-17 | メディカル リサーチ カウンシル | 多様性の生成方法 |
| JP2005539030A (ja) * | 2002-08-14 | 2005-12-22 | アストラゼネカ・アクチエボラーグ | ニコチン性アセチルコリン作用剤としてのアリール置換ジアザビシクロアルカン |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007520527A (ja) * | 2004-02-04 | 2007-07-26 | ノイロサーチ アクティーゼルスカブ | ニコチン性アセチルコリン受容体リガンドとしてのジアザ２環式アリール誘導体 |
| JP2010509230A (ja) * | 2006-11-02 | 2010-03-25 | ターガセプト，インコーポレイテッド | ニコチン性アセチルコリン受容体サブタイプ選択的なジアザビシクロアルカンのアミド |
| JP2013056919A (ja) * | 2006-11-02 | 2013-03-28 | Targacept Inc | ニコチン性アセチルコリン受容体サブタイプ選択的なジアザビシクロアルカンのアミド |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2518675A1 (en) | 2004-09-10 |
| US7678788B2 (en) | 2010-03-16 |
| MXPA05006861A (es) | 2005-12-12 |
| AU2004215658B2 (en) | 2010-06-24 |
| DE602004023586D1 (de) | 2009-11-26 |
| NZ540998A (en) | 2008-06-30 |
| EP1599476A1 (en) | 2005-11-30 |
| BRPI0407216A (pt) | 2006-01-24 |
| WO2004076453A1 (en) | 2004-09-10 |
| AU2004215658A1 (en) | 2004-09-10 |
| ATE445618T1 (de) | 2009-10-15 |
| EP1599476B1 (en) | 2009-10-14 |
| US20060148789A1 (en) | 2006-07-06 |
| US20100130483A1 (en) | 2010-05-27 |
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