OA10996A - Pyrrolidinyl and pyrrolinyl ethylamine compounds as kappa agonists - Google Patents
Pyrrolidinyl and pyrrolinyl ethylamine compounds as kappa agonists Download PDFInfo
- Publication number
- OA10996A OA10996A OA9900057A OA9900057A OA10996A OA 10996 A OA10996 A OA 10996A OA 9900057 A OA9900057 A OA 9900057A OA 9900057 A OA9900057 A OA 9900057A OA 10996 A OA10996 A OA 10996A
- Authority
- OA
- OAPI
- Prior art keywords
- methylamino
- phenylethyl
- hydroxypyrrolidin
- propylbenzamide
- hydroxy
- Prior art date
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- 239000000556 agonist Substances 0.000 title claims abstract description 17
- 125000000719 pyrrolidinyl group Chemical group 0.000 title description 3
- KRRLFZPRZPZNPW-UHFFFAOYSA-N n-ethyl-2,3-dihydropyrrol-1-amine Chemical class CCNN1CCC=C1 KRRLFZPRZPZNPW-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 31
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 17
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 144
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 90
- 239000000203 mixture Substances 0.000 claims description 77
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 66
- -1 haloCi-Cf Chemical group 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- 125000005843 halogen group Chemical group 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 102000048260 kappa Opioid Receptors Human genes 0.000 claims description 7
- 108020001588 κ-opioid receptors Proteins 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- IZRDLZYOQSBCNG-UHFFFAOYSA-N 2-propylbenzamide Chemical compound CCCC1=CC=CC=C1C(N)=O IZRDLZYOQSBCNG-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 230000003444 anaesthetic effect Effects 0.000 claims description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000004090 neuroprotective agent Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- XXZDIDFBKZKGQB-RYUDHWBXSA-N (1r)-2-[(3s)-3-fluoropyrrolidin-1-yl]-1-phenylethanol Chemical compound C([C@H](O)C=1C=CC=CC=1)N1CC[C@H](F)C1 XXZDIDFBKZKGQB-RYUDHWBXSA-N 0.000 claims description 3
- XXZDIDFBKZKGQB-VXGBXAGGSA-N (1s)-2-[(3r)-3-fluoropyrrolidin-1-yl]-1-phenylethanol Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1CC[C@@H](F)C1 XXZDIDFBKZKGQB-VXGBXAGGSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000003193 general anesthetic agent Substances 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000005543 phthalimide group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 9
- HVEKOIABBLJFPQ-MRVPVSSYSA-N n-[(2r)-2-hydroxypropyl]benzamide Chemical compound C[C@@H](O)CNC(=O)C1=CC=CC=C1 HVEKOIABBLJFPQ-MRVPVSSYSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 150000003235 pyrrolidines Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 102
- 239000007787 solid Substances 0.000 description 77
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 61
- 150000001412 amines Chemical class 0.000 description 56
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
- 239000000243 solution Substances 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- 101150041968 CDC13 gene Proteins 0.000 description 38
- 239000003921 oil Substances 0.000 description 38
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- 235000010233 benzoic acid Nutrition 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 28
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- 238000004440 column chromatography Methods 0.000 description 24
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- 229910002027 silica gel Inorganic materials 0.000 description 23
- 229960001866 silicon dioxide Drugs 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 18
- 239000012442 inert solvent Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
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- 238000012360 testing method Methods 0.000 description 9
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Substances [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
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- 239000002632 kappa opiate receptor agonist Substances 0.000 description 7
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Mechanical Coupling Of Light Guides (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| IBPCT/IB96/00957 | 1996-09-18 |
Publications (1)
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| OA10996A true OA10996A (en) | 2001-11-06 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU3053199A (en) * | 1998-04-01 | 1999-10-25 | Ono Pharmaceutical Co. Ltd. | Fused thiophene derivatives and drugs containing the same as the active ingredient |
| IL130429A0 (en) * | 1998-08-24 | 2000-06-01 | Pfizer Prod Inc | Process for preparing pyrrolidinyl hydroxamic acid compounds |
| CA2445874A1 (en) * | 2001-04-30 | 2002-11-07 | Fumitaka Ito | Process for preparing hydroxypyrrolidinyl ethylamine compounds useful as kappa agonists |
| AU2003248351A1 (en) * | 2002-02-28 | 2003-09-09 | Pfizer Products Inc. | Crystalline anhydrous and monohydrate benzoate salts of (2's,3s)-3-hydroxy-n-{2{n-methyl-n-4-(n-propylamino-carbonyl)phenyl)amino-2-phenyl}-ethylpyrrolidine |
| AU2003269399A1 (en) * | 2002-11-01 | 2004-05-25 | Pfizer Products Inc. | Process for the preparation of pyrrolidinyl ethylamine compounds via a copper-mediated aryl amination |
| JP2007531753A (ja) * | 2004-03-31 | 2007-11-08 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 非イミダゾール系複素環式化合物 |
| US7746514B2 (en) * | 2004-04-14 | 2010-06-29 | Hung-Yi Hsu | Scanner and exposure control method thereof |
| RU2303448C2 (ru) * | 2005-04-28 | 2007-07-27 | Государственное образовательное учреждение высшего профессионального образования "Пермская государственная фармацевтическая академия Федерального агентства по здравоохранению и социальному развитию" (ГОУ ВПО ПГФА Росздрава) | 3-гидрокси-5-(3-нитрофенил)-4-(4-хлорбензоил)-1-(2-диэтиламиноэтил)-3-пирролин-2-она гидрохлорид, проявляющий противовоспалительную активность |
| US20070213319A1 (en) * | 2006-01-11 | 2007-09-13 | Angion Biomedica Corporation | Modulators of hepatocyte growth factor/c-Met activity |
| CA2653940C (en) | 2006-05-30 | 2015-07-14 | Janssen Pharmaceutica N.V. | Substituted pyridyl amide compounds as modulators of the histamine h3 receptor |
| AU2007265238A1 (en) * | 2006-06-29 | 2008-01-03 | Janssen Pharmaceutica N.V. | Substituted benzamide modulators of the histamine H3 receptor |
| EA018582B1 (ru) | 2007-11-20 | 2013-09-30 | Янссен Фармацевтика Н.В. | Соединения циклоалкилокси- и гетероциклоалкилоксипиридина как модуляторы гистаминового рецептора н |
| RU2413512C1 (ru) * | 2009-07-29 | 2011-03-10 | Федеральное государственное автономное образовательное учреждение высшего профессионального образования "ЮЖНЫЙ ФЕДЕРАЛЬНЫЙ УНИВЕРСИТЕТ" | Средство, обладающее каппа-опиоидной агонистической активностью |
| WO2021163683A1 (en) | 2020-02-14 | 2021-08-19 | President And Fellows Of Harvard College | Inhibitors of nicotinamide n-methyltransferase, compositions and uses thereof |
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| GB8801304D0 (en) * | 1988-01-21 | 1988-02-17 | Ici Plc | Diamine compounds |
| DE3935371A1 (de) * | 1988-12-23 | 1990-07-05 | Merck Patent Gmbh | Stickstoffhaltige ringverbindungen |
| US5232978A (en) * | 1988-12-23 | 1993-08-03 | Merck Patent Gesellschaft Mit Beschrankter Haftung | 1-(2-arylethyl)-pyrrolidines |
| DE4034785A1 (de) * | 1990-11-02 | 1992-05-07 | Merck Patent Gmbh | 1-(2-arylethyl)-pyrrolidine |
| WO1994018165A1 (en) | 1993-02-12 | 1994-08-18 | Pfizer Inc. | Sulfonamide compounds as opioid k-receptor agonists |
| IL117440A0 (en) | 1995-03-31 | 1996-07-23 | Pfizer | Pyrrolidinyl hydroxamic acid compounds and their production process |
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