CA2480378A1 - Novel azacyclic ethynyl derivatives - Google Patents
Novel azacyclic ethynyl derivatives Download PDFInfo
- Publication number
- CA2480378A1 CA2480378A1 CA002480378A CA2480378A CA2480378A1 CA 2480378 A1 CA2480378 A1 CA 2480378A1 CA 002480378 A CA002480378 A CA 002480378A CA 2480378 A CA2480378 A CA 2480378A CA 2480378 A1 CA2480378 A1 CA 2480378A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- alkyl
- cycloalkyl
- aryl
- cycloalkoxy
- Prior art date
- 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.)
- Abandoned
Links
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 title claims abstract description 72
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 89
- 201000010099 disease Diseases 0.000 claims abstract description 48
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- 238000011282 treatment Methods 0.000 claims abstract description 25
- 102000005962 receptors Human genes 0.000 claims abstract description 15
- 108020003175 receptors Proteins 0.000 claims abstract description 15
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- 239000000126 substance Substances 0.000 claims abstract description 12
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- 230000004770 neurodegeneration Effects 0.000 claims abstract description 6
- 230000016160 smooth muscle contraction Effects 0.000 claims abstract description 6
- -1 cyano, amino Chemical group 0.000 claims description 237
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 125000000304 alkynyl group Chemical group 0.000 claims description 61
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 55
- 125000003545 alkoxy group Chemical group 0.000 claims description 51
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 49
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 49
- 150000002367 halogens Chemical class 0.000 claims description 49
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 49
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 48
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- 238000000034 method Methods 0.000 claims description 36
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 22
- 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 16
- 125000004122 cyclic group Chemical group 0.000 claims description 16
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
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- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 3
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 3
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 claims description 3
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- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 125000003943 azolyl group Chemical group 0.000 claims description 3
- 125000003828 azulenyl group Chemical group 0.000 claims description 3
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
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- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 150000004291 polyenes Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
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- 108090000765 processed proteins & peptides Proteins 0.000 description 1
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- GHUURDQYRGVEHX-UHFFFAOYSA-N prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1 GHUURDQYRGVEHX-UHFFFAOYSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
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- 229940075554 sorbate Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 229910021653 sulphate ion Inorganic materials 0.000 description 1
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- 239000012730 sustained-release form Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
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- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 150000005671 trienes Chemical class 0.000 description 1
- 208000037820 vascular cognitive impairment Diseases 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
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (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)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Addiction (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Pregnancy & Childbirth (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200200691 | 2002-05-07 | ||
| DKPA200200691 | 2002-05-07 | ||
| PCT/DK2003/000294 WO2003094830A2 (en) | 2002-05-07 | 2003-05-06 | Novel azacyclic ethynyl derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2480378A1 true CA2480378A1 (en) | 2003-11-20 |
Family
ID=29414627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002480378A Abandoned CA2480378A1 (en) | 2002-05-07 | 2003-05-06 | Novel azacyclic ethynyl derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US7378526B2 (enExample) |
| EP (1) | EP1506205B1 (enExample) |
| JP (1) | JP2005524712A (enExample) |
| CN (1) | CN100522976C (enExample) |
| AT (1) | ATE401334T1 (enExample) |
| AU (1) | AU2003222738B2 (enExample) |
| CA (1) | CA2480378A1 (enExample) |
| DE (1) | DE60322212D1 (enExample) |
| MX (1) | MXPA04010965A (enExample) |
| NZ (1) | NZ535641A (enExample) |
| WO (1) | WO2003094830A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| CA2499128C (en) | 2002-09-25 | 2012-07-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
| PL1697378T3 (pl) | 2003-12-22 | 2008-04-30 | Memory Pharm Corp | Indole, 1h-indazole, 1,2-benzoizoksazole i 1,2-benzoizotiazole oraz ich wytwarzanie i zastosowania |
| WO2005092890A2 (en) | 2004-03-25 | 2005-10-06 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| DE602005024677D1 (de) | 2004-04-22 | 2010-12-23 | Memory Pharm Corp | Indole, 1h-indazole, 1,2-benzisoxazole, 1,2-benzoisothiazole, deren herstellung und verwendungen |
| RU2386633C2 (ru) | 2004-05-07 | 2010-04-20 | Мемори Фармасьютиклз Корпорейшн | 1h-индазолы, бензотиазолы, 1, 2-бензоизоксазолы, 1, 2-бензоизотиазолы и хромоны и их получение и применения |
| JP2008525464A (ja) | 2004-12-22 | 2008-07-17 | メモリー・ファーマシューティカルズ・コーポレイション | α−７ニコチン性受容体リガンド並びにその製造及び使用 |
| AU2010319927B2 (en) * | 2009-10-29 | 2015-01-22 | Janssen Pharmaceutica Nv | Alkynyl derivatives useful as DPP-1 inhibitors |
| TWI519532B (zh) | 2010-05-17 | 2016-02-01 | 艾維沃製藥公司 | （Ｒ）－７－氯－Ｎ－（啶－３－基）苯並［b］噻吩－２－羧醯胺鹽酸鹽單水合物之結晶形體 |
| RU2017136693A (ru) | 2012-05-08 | 2019-02-08 | Форум Фармасьютикалз, Инк. | Способы поддержания, лечения или улучшения когнитивной функции |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9218334D0 (en) * | 1992-08-28 | 1992-10-14 | Ici Plc | Heterocyclic compounds |
| GB9226573D0 (en) * | 1992-12-21 | 1993-02-17 | Ici Plc | Heterocyclic compounds |
| US5616712A (en) * | 1995-05-16 | 1997-04-01 | Allergan | Acetylenes disubstituted with a phenyl or heteroaryl group and a 2-thio-1,2,3,4-tetrahdroquinolinyl, 2-alkylthio-3,4-dihydroquinolinyl or 2-alkoxy-3,4-dihydroquinolinyl group having retinoid-like biological activity |
| HUP9802433A3 (en) * | 1995-10-13 | 2000-03-28 | Neurosearch As | 8-azabicyclo[3.2.1]oct-2-ene derivatives, their preparation and use |
| KR100589872B1 (ko) * | 1997-05-30 | 2006-06-15 | 뉴로서치 에이/에스 | 8-아자비사이클로(3,2,1)옥트-2-엔 유도체 및 이의 제조방법 |
| DE69914935T2 (de) * | 1998-11-27 | 2009-10-01 | Neurosearch A/S | 8-azabicyclo[3.2.1]okt-2-en- und -oktanderivate |
| UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| JP4815083B2 (ja) | 1999-08-31 | 2011-11-16 | メルク・シャープ・エンド・ドーム・コーポレイション | 複素環化合物およびそれの使用方法 |
| JP5154728B2 (ja) * | 2000-07-24 | 2013-02-27 | クレニツキー・ファーマシューティカルズ，インコーポレイテッド | 神経栄養活性を有する置換５−アルキニルピリミジン |
| US6624167B1 (en) * | 2000-08-04 | 2003-09-23 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| EP1358177B1 (en) * | 2000-10-13 | 2006-08-02 | NeuroSearch A/S | Treatment of affective disorders by the combined action of a nicotinic receptor agonist and a monoaminergic substance |
| RU2288919C2 (ru) * | 2001-10-02 | 2006-12-10 | Акадиа Фармасьютикалз, Инк. | Производные бензимидазолидинона в качестве агентов мускариновых рецепторов |
| RU2004110717A (ru) | 2001-10-17 | 2005-10-20 | Юсиби, С.А. (Be) | Производные хинуклидина, способы их получения и их применение в качестве и нгибиторов м2- и/или м3- мускариновых рецепторов |
| KR100432283B1 (ko) * | 2001-10-27 | 2004-05-22 | 한국과학기술연구원 | 무스카린성 아세틸콜린 수용체에 작용하는테트라하이드로피리딘 유도체 |
-
2003
- 2003-05-06 AU AU2003222738A patent/AU2003222738B2/en not_active Ceased
- 2003-05-06 MX MXPA04010965A patent/MXPA04010965A/es active IP Right Grant
- 2003-05-06 DE DE60322212T patent/DE60322212D1/de not_active Expired - Lifetime
- 2003-05-06 NZ NZ535641A patent/NZ535641A/en not_active IP Right Cessation
- 2003-05-06 CN CNB03810184XA patent/CN100522976C/zh not_active Expired - Fee Related
- 2003-05-06 CA CA002480378A patent/CA2480378A1/en not_active Abandoned
- 2003-05-06 WO PCT/DK2003/000294 patent/WO2003094830A2/en not_active Ceased
- 2003-05-06 EP EP03718655A patent/EP1506205B1/en not_active Expired - Lifetime
- 2003-05-06 AT AT03718655T patent/ATE401334T1/de not_active IP Right Cessation
- 2003-05-06 US US10/513,416 patent/US7378526B2/en not_active Expired - Fee Related
- 2003-05-06 JP JP2004502919A patent/JP2005524712A/ja not_active Ceased
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2008
- 2008-03-25 US US12/076,929 patent/US7667040B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7667040B2 (en) | 2010-02-23 |
| ATE401334T1 (de) | 2008-08-15 |
| WO2003094830A2 (en) | 2003-11-20 |
| WO2003094830A3 (en) | 2004-03-18 |
| US20050171078A1 (en) | 2005-08-04 |
| US7378526B2 (en) | 2008-05-27 |
| CN100522976C (zh) | 2009-08-05 |
| CN1649884A (zh) | 2005-08-03 |
| JP2005524712A (ja) | 2005-08-18 |
| DE60322212D1 (de) | 2008-08-28 |
| US20080188519A1 (en) | 2008-08-07 |
| NZ535641A (en) | 2006-10-27 |
| EP1506205B1 (en) | 2008-07-16 |
| HK1079528A1 (en) | 2006-04-07 |
| AU2003222738B2 (en) | 2009-09-17 |
| MXPA04010965A (es) | 2005-01-25 |
| AU2003222738A1 (en) | 2003-11-11 |
| EP1506205A2 (en) | 2005-02-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20111201 |