ES2392200T3 - Ésteres de diarilo como antagonistas del receptor opiáceo - Google Patents
Ésteres de diarilo como antagonistas del receptor opiáceo Download PDFInfo
- Publication number
- ES2392200T3 ES2392200T3 ES08153866T ES08153866T ES2392200T3 ES 2392200 T3 ES2392200 T3 ES 2392200T3 ES 08153866 T ES08153866 T ES 08153866T ES 08153866 T ES08153866 T ES 08153866T ES 2392200 T3 ES2392200 T3 ES 2392200T3
- Authority
- ES
- Spain
- Prior art keywords
- mmol
- compound
- phenoxy
- methyl
- title compound
- 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.)
- Expired - Lifetime
Links
- 229940123257 Opioid receptor antagonist Drugs 0.000 title description 5
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 title description 2
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- QWNDOCKIKKQJNN-UHFFFAOYSA-N 6-[2-fluoro-4-[[2-(oxan-4-yl)ethylamino]methyl]phenoxy]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1OC(C(=C1)F)=CC=C1CNCCC1CCOCC1 QWNDOCKIKKQJNN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 208000007848 Alcoholism Diseases 0.000 claims abstract description 6
- 201000007930 alcohol dependence Diseases 0.000 claims abstract description 5
- 229940079593 drug Drugs 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- ZGCYVRNZWGUXNQ-UHFFFAOYSA-N Bevenopran Chemical compound C=1C=C(OC=2N=CC(=NC=2)C(N)=O)C(OC)=CC=1CNCCC1CCOCC1 ZGCYVRNZWGUXNQ-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 222
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 198
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
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- 238000006243 chemical reaction Methods 0.000 description 61
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 239000012141 concentrate Substances 0.000 description 51
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 45
- -1 bicyclic phenyl-piperidine analogs Chemical class 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
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- 125000003118 aryl group Chemical group 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- 239000002904 solvent Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000012279 sodium borohydride Substances 0.000 description 20
- 229910000033 sodium borohydride Inorganic materials 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 239000004480 active ingredient Substances 0.000 description 19
- 150000001412 amines Chemical class 0.000 description 19
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical class OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- 125000000217 alkyl group Chemical group 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 102000003840 Opioid Receptors Human genes 0.000 description 14
- 108090000137 Opioid Receptors Proteins 0.000 description 14
- 241000700159 Rattus Species 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 13
- 150000001299 aldehydes Chemical class 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 235000015320 potassium carbonate Nutrition 0.000 description 13
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 125000000623 heterocyclic group Chemical group 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 238000002531 positive electrospray ionisation time-of-flight mass spectrometry Methods 0.000 description 12
- 238000006268 reductive amination reaction Methods 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 11
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- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- 108020001588 κ-opioid receptors Proteins 0.000 description 11
- 108020001612 μ-opioid receptors Proteins 0.000 description 11
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- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 10
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- 102000048260 kappa Opioid Receptors Human genes 0.000 description 10
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
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- NQRQAZFETBXHCA-UHFFFAOYSA-N tert-butyl n-[[4-(6-carbamoylpyridin-3-yl)oxyphenyl]methyl]-n-(2-phenylethyl)carbamate Chemical compound C=1C=C(OC=2C=NC(=CC=2)C(N)=O)C=CC=1CN(C(=O)OC(C)(C)C)CCC1=CC=CC=C1 NQRQAZFETBXHCA-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A61P1/12—Antidiarrhoeals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41215802P | 2002-09-19 | 2002-09-19 | |
| US412158P | 2002-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2392200T3 true ES2392200T3 (es) | 2012-12-05 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| ES08153866T Expired - Lifetime ES2392200T3 (es) | 2002-09-19 | 2003-09-17 | Ésteres de diarilo como antagonistas del receptor opiáceo |
| ES03751877T Expired - Lifetime ES2305491T3 (es) | 2002-09-19 | 2003-09-17 | Eteres de diarilo como antagonistas de receptores de opioides. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES03751877T Expired - Lifetime ES2305491T3 (es) | 2002-09-19 | 2003-09-17 | Eteres de diarilo como antagonistas de receptores de opioides. |
Country Status (29)
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| EP (2) | EP1562595B1 (enExample) |
| JP (1) | JP4646628B2 (enExample) |
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- 2003-09-17 AR ARP030103376A patent/AR042423A1/es active IP Right Grant
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