ZA200205991B - 1,3-disubstituted pyrrolidines as alpha-2-adrenoceptor antagonists. - Google Patents
1,3-disubstituted pyrrolidines as alpha-2-adrenoceptor antagonists. Download PDFInfo
- Publication number
- ZA200205991B ZA200205991B ZA200205991A ZA200205991A ZA200205991B ZA 200205991 B ZA200205991 B ZA 200205991B ZA 200205991 A ZA200205991 A ZA 200205991A ZA 200205991 A ZA200205991 A ZA 200205991A ZA 200205991 B ZA200205991 B ZA 200205991B
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- ZA
- South Africa
- Prior art keywords
- alkyl
- hydrogen
- compound
- free base
- addition salt
- Prior art date
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- -1 1,3-disubstituted pyrrolidines Chemical class 0.000 title claims description 16
- 239000005557 antagonist Substances 0.000 title claims description 9
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 title description 2
- 102000015006 alpha2-adrenergic receptor activity proteins Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical group 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 239000012458 free base Substances 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 108060003345 Adrenergic Receptor Proteins 0.000 claims description 6
- 102000017910 Adrenergic receptor Human genes 0.000 claims description 6
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 230000002152 alkylating effect Effects 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
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- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- A—HUMAN NECESSITIES
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- A61P25/22—Anxiolytics
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/08—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing alicyclic rings
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- C—CHEMISTRY; METALLURGY
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Organic Chemistry (AREA)
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- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Hematology (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB0002100.6A GB0002100D0 (en) | 2000-01-28 | 2000-01-28 | Organic compounds |
Publications (1)
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|---|---|
| ZA200205991B true ZA200205991B (en) | 2003-10-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| ZA200205991A ZA200205991B (en) | 2000-01-28 | 2002-07-26 | 1,3-disubstituted pyrrolidines as alpha-2-adrenoceptor antagonists. |
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| EP (1) | EP1257547B1 (cs) |
| JP (1) | JP2003523353A (cs) |
| KR (1) | KR20020069375A (cs) |
| CN (2) | CN1178935C (cs) |
| AR (1) | AR029463A1 (cs) |
| AT (1) | ATE384715T1 (cs) |
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| BR (1) | BR0107888A (cs) |
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| ES (1) | ES2296763T3 (cs) |
| GB (1) | GB0002100D0 (cs) |
| HU (1) | HUP0203836A3 (cs) |
| IL (1) | IL150550A0 (cs) |
| MX (1) | MXPA02007318A (cs) |
| MY (1) | MY128639A (cs) |
| NO (1) | NO20023485L (cs) |
| NZ (1) | NZ520342A (cs) |
| PE (1) | PE20011068A1 (cs) |
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| RU (1) | RU2002121646A (cs) |
| SK (1) | SK10802002A3 (cs) |
| WO (1) | WO2001055132A1 (cs) |
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Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB0002100D0 (en) * | 2000-01-28 | 2000-03-22 | Novartis Ag | Organic compounds |
| US6436972B1 (en) | 2000-04-10 | 2002-08-20 | Dalhousie University | Pyridones and their use as modulators of serine hydrolase enzymes |
| AU2003216954A1 (en) * | 2002-03-29 | 2003-10-13 | Orion Corporation | Treatment of dependence and dependence related withdrawal symptoms |
| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| JP2008037850A (ja) * | 2006-08-10 | 2008-02-21 | Mitsubishi Tanabe Pharma Corp | 新規置換ピペリジン誘導体 |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| RU2336901C1 (ru) * | 2007-08-10 | 2008-10-27 | Владимир Павлович Чехонин | Противоопухолевое средство на основе иммунолипосомальной биологической конструкции, способ его получения и векторной доставки в центральную нервную систему при опухолевом процессе |
| TWI445532B (zh) | 2007-09-14 | 2014-07-21 | Janssen Pharmaceuticals Inc | １’，３’－二取代－４－苯基－３，４，５，６－四氫－２ｈ，１’ｈ－〔１，４’〕聯吡啶基－２’－酮化物 |
| US8273900B2 (en) * | 2008-08-07 | 2012-09-25 | Novartis Ag | Organic compounds |
| US8691849B2 (en) | 2008-09-02 | 2014-04-08 | Janssen Pharmaceuticals, Inc. | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
| CN102232074B (zh) | 2008-11-28 | 2014-12-03 | 奥梅-杨森制药有限公司 | 作为代谢性谷氨酸盐受体调节剂的吲哚和苯并噁嗪衍生物 |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2409006T3 (es) | 2009-05-12 | 2013-06-24 | Janssen Pharmaceuticals Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de los receptores mGluR2 |
| EP2430022B1 (en) | 2009-05-12 | 2013-11-20 | Janssen Pharmaceuticals, Inc. | 1,2,4-Triazolo[4,3-a]pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders |
| AU2011328194B2 (en) | 2010-11-08 | 2015-04-16 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors |
| JP5852665B2 (ja) | 2010-11-08 | 2016-02-03 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | １，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用 |
| WO2012062759A1 (en) | 2010-11-08 | 2012-05-18 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| GB2503187A (en) * | 2011-09-15 | 2013-12-25 | Univ Sussex | Composition for use in the treatment of neurodevelopmental disorders |
| WO2014080290A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Cyclic amines as bromodomain inhibitors |
| WO2014080291A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Biaryl derivatives as bromodomain inhibitors |
| CN105073744B (zh) * | 2012-12-21 | 2019-11-08 | 齐尼思表观遗传学有限公司 | 作为溴结构域抑制剂的新型杂环化合物 |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| EA035601B1 (ru) | 2013-06-21 | 2020-07-14 | Зенит Эпидженетикс Лтд. | Бициклические ингибиторы бромодомена |
| CN105473581B (zh) | 2013-06-21 | 2019-04-23 | 齐尼思表观遗传学有限公司 | 作为溴结构域抑制剂的新取代的双环化合物 |
| KR20160038008A (ko) | 2013-07-31 | 2016-04-06 | 제니쓰 에피제네틱스 코포레이션 | 브로모도메인 억제제로서 신규 퀴나졸리논 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| LT3096790T (lt) | 2014-01-21 | 2019-10-10 | Janssen Pharmaceutica, N.V. | Deriniai, apimantys 2 potipio metabotropinio glutamaterginio receptoriaus teigiamus alosterinius moduliatorius arba ortosterinius agonistus, ir jų panaudojimas |
| UA127921C2 (uk) | 2014-01-21 | 2024-02-14 | Янссен Фармацевтика Нв | Комбінації, які містять позитивні алостеричні модулятори або ортостеричні агоністи метаботропного глутаматергічного рецептора 2 підтипу, та їх застосування |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| WO2016087942A1 (en) | 2014-12-01 | 2016-06-09 | Zenith Epigenetics Corp. | Substituted pyridines as bromodomain inhibitors |
| EP3230277B1 (en) | 2014-12-11 | 2019-09-18 | Zenith Epigenetics Ltd. | Substituted heterocycles as bromodomain inhibitors |
| JP2017538721A (ja) | 2014-12-17 | 2017-12-28 | ゼニス・エピジェネティクス・リミテッドＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｌｔｄ． | ブロモドメインの阻害剤 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| FI95572C (fi) | 1987-06-22 | 1996-02-26 | Eisai Co Ltd | Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi |
| US5185364A (en) * | 1988-01-15 | 1993-02-09 | Abbott Laboratories | Aminomethyl-chroman and -thiochroman compounds |
| ES2157204T3 (es) | 1991-04-17 | 2001-08-16 | Upjohn Co | Derivados de (s)-3-fenilpiperidina sustituidos, su preparacion y uso como antagonistas de autorreceptores de dopamina. |
| GB9113031D0 (en) | 1991-06-17 | 1991-08-07 | Smithkline Beecham Plc | Compounds |
| FR2687146B1 (fr) * | 1992-02-12 | 1994-04-01 | Adir Cie | Nouveaux derives de pyrrolidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| DE69531098T2 (de) | 1994-03-09 | 2004-04-29 | Novo Nordisk A/S | Piperidine und pyrrolidine |
| SE9802546D0 (sv) * | 1998-07-15 | 1998-07-15 | Ross Nicholas Waters | Medicinal product and method for treatment and prevention of dyskinesia |
| IT1303737B1 (it) | 1998-11-11 | 2001-02-23 | Smithkline Beecham Spa | Derivati fenilpiperidinici procedimento per la loro preparazione eloro uso come ligandi del recettore orl-1. |
| GB0002100D0 (en) * | 2000-01-28 | 2000-03-22 | Novartis Ag | Organic compounds |
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2000
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2001
- 2001-01-23 MY MYPI20010309A patent/MY128639A/en unknown
- 2001-01-25 AR ARP010100318A patent/AR029463A1/es unknown
- 2001-01-26 HU HU0203836A patent/HUP0203836A3/hu unknown
- 2001-01-26 CZ CZ20022581A patent/CZ20022581A3/cs unknown
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- 2001-01-26 DE DE60132558T patent/DE60132558T2/de not_active Expired - Fee Related
- 2001-01-26 JP JP2001560991A patent/JP2003523353A/ja active Pending
- 2001-01-26 US US10/182,090 patent/US7012085B2/en not_active Expired - Fee Related
- 2001-01-26 ES ES01946858T patent/ES2296763T3/es not_active Expired - Lifetime
- 2001-01-26 PE PE2001000086A patent/PE20011068A1/es not_active Application Discontinuation
- 2001-01-26 CA CA002398794A patent/CA2398794C/en not_active Expired - Fee Related
- 2001-01-26 SK SK1080-2002A patent/SK10802002A3/sk unknown
- 2001-01-26 RU RU2002121646/04A patent/RU2002121646A/ru not_active Application Discontinuation
- 2001-01-26 CN CNB018042341A patent/CN1178935C/zh not_active Expired - Fee Related
- 2001-01-26 MX MXPA02007318A patent/MXPA02007318A/es active IP Right Grant
- 2001-01-26 AU AU28501/01A patent/AU768844B2/en not_active Ceased
- 2001-01-26 WO PCT/EP2001/000861 patent/WO2001055132A1/en not_active Ceased
- 2001-01-26 CN CNB2004100839164A patent/CN1305847C/zh not_active Expired - Fee Related
- 2001-01-26 EP EP01946858A patent/EP1257547B1/en not_active Expired - Lifetime
- 2001-01-26 PT PT01946858T patent/PT1257547E/pt unknown
- 2001-01-26 AT AT01946858T patent/ATE384715T1/de not_active IP Right Cessation
- 2001-01-26 BR BR0107888-7A patent/BR0107888A/pt not_active Application Discontinuation
- 2001-01-26 KR KR1020027009705A patent/KR20020069375A/ko not_active Withdrawn
- 2001-01-26 PL PL356265A patent/PL202473B1/pl not_active IP Right Cessation
- 2001-01-26 NZ NZ520342A patent/NZ520342A/en unknown
- 2001-01-29 CO CO01006310A patent/CO5261521A1/es not_active Application Discontinuation
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2002
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- 2002-07-26 ZA ZA200205991A patent/ZA200205991B/en unknown
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