KR100856622B1 - 포스포디에스테라제 4 억제제 - Google Patents
포스포디에스테라제 4 억제제 Download PDFInfo
- Publication number
- KR100856622B1 KR100856622B1 KR1020037009624A KR20037009624A KR100856622B1 KR 100856622 B1 KR100856622 B1 KR 100856622B1 KR 1020037009624 A KR1020037009624 A KR 1020037009624A KR 20037009624 A KR20037009624 A KR 20037009624A KR 100856622 B1 KR100856622 B1 KR 100856622B1
- Authority
- KR
- South Korea
- Prior art keywords
- pyridylmethyl
- diphenylamine
- methoxy
- cyclopentyloxy
- carbon atoms
- Prior art date
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- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 16
- -1 N-substituted anilines Chemical class 0.000 claims abstract description 622
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims abstract description 209
- 150000001875 compounds Chemical class 0.000 claims abstract description 207
- 239000003112 inhibitor Substances 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 225
- 125000000217 alkyl group Chemical group 0.000 claims description 178
- 229910052736 halogen Inorganic materials 0.000 claims description 136
- 150000002367 halogens Chemical class 0.000 claims description 135
- 229940035422 diphenylamine Drugs 0.000 claims description 105
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 94
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 77
- 125000004043 oxo group Chemical group O=* 0.000 claims description 76
- 239000000203 mixture Substances 0.000 claims description 73
- 125000003545 alkoxy group Chemical group 0.000 claims description 72
- 125000006413 ring segment Chemical group 0.000 claims description 67
- 125000003118 aryl group Chemical group 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 48
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 47
- 150000001412 amines Chemical class 0.000 claims description 44
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 40
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 229920006395 saturated elastomer Polymers 0.000 claims description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 125000002252 acyl group Chemical group 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
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- 125000002837 carbocyclic group Chemical group 0.000 claims description 19
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 18
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- 125000004434 sulfur atom Chemical group 0.000 claims description 17
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 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 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 11
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 10
- PNIUJOQYAGLPHM-UHFFFAOYSA-N 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OC1CCCC1 PNIUJOQYAGLPHM-UHFFFAOYSA-N 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 9
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- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
- BHMSBBTXYYMQGC-UHFFFAOYSA-N C(C)OC1=C(C=CC=C1)N(CC=1C=NC=CC=1OC)C1=CC=CC=C1 Chemical compound C(C)OC1=C(C=CC=C1)N(CC=1C=NC=CC=1OC)C1=CC=CC=C1 BHMSBBTXYYMQGC-UHFFFAOYSA-N 0.000 claims description 6
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- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- UGWWTKUPDVMIAT-UHFFFAOYSA-N 3-[3-(cyclopropylmethoxy)-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(O)=O)C=C1OCC1CC1 UGWWTKUPDVMIAT-UHFFFAOYSA-N 0.000 claims description 5
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- XQVMANRSBUNGSR-UHFFFAOYSA-N 4-[3-(cyclopropylmethoxy)-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoic acid Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=CC(=CC=2)C(O)=O)C=C1OCC1CC1 XQVMANRSBUNGSR-UHFFFAOYSA-N 0.000 claims description 5
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- AXZNPNQZVQZTIM-UHFFFAOYSA-N tert-butyl 3-[3-cyclopentyloxy-4-methoxy-n-(pyridin-3-ylmethyl)anilino]benzoate Chemical compound COC1=CC=C(N(CC=2C=NC=CC=2)C=2C=C(C=CC=2)C(=O)OC(C)(C)C)C=C1OC1CCCC1 AXZNPNQZVQZTIM-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
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- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/88—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to a carbon atom of a ring other than a six-membered aromatic ring
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
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- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/92—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the nitrogen atom of at least one of the amino groups being further bound to a carbon atom of a six-membered aromatic ring
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- 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
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- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
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- C07D401/00—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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—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
- 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
- C07D405/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Pulmonology (AREA)
- Psychology (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26265101P | 2001-01-22 | 2001-01-22 | |
US60/262,651 | 2001-01-22 | ||
US26719601P | 2001-02-08 | 2001-02-08 | |
US60/267,196 | 2001-02-08 | ||
US30614001P | 2001-07-19 | 2001-07-19 | |
US60/306,140 | 2001-07-19 | ||
PCT/US2002/001508 WO2002074726A2 (en) | 2001-01-22 | 2002-01-22 | Aniline derivatives useful as phosphodiesterase 4 inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20040064606A KR20040064606A (ko) | 2004-07-19 |
KR100856622B1 true KR100856622B1 (ko) | 2008-09-03 |
Family
ID=27401532
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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KR1020037009624A KR100856622B1 (ko) | 2001-01-22 | 2002-01-22 | 포스포디에스테라제 4 억제제 |
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EP (1) | EP1353907A2 (es) |
JP (1) | JP4223287B2 (es) |
KR (1) | KR100856622B1 (es) |
CN (1) | CN100378075C (es) |
AU (1) | AU2002303078B2 (es) |
BG (1) | BG108003A (es) |
BR (1) | BR0206943A (es) |
CA (1) | CA2435847A1 (es) |
CL (1) | CL2004001165A1 (es) |
CZ (1) | CZ20031986A3 (es) |
EE (1) | EE05362B1 (es) |
HK (1) | HK1066215A1 (es) |
HR (1) | HRP20030662A2 (es) |
HU (1) | HUP0302793A3 (es) |
IL (1) | IL156958A0 (es) |
MA (1) | MA25996A1 (es) |
MX (1) | MXPA03006519A (es) |
NO (1) | NO329548B1 (es) |
NZ (1) | NZ527081A (es) |
PL (1) | PL373301A1 (es) |
SK (1) | SK9152003A3 (es) |
WO (1) | WO2002074726A2 (es) |
YU (1) | YU57603A (es) |
ZA (1) | ZA200305623B (es) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7153871B2 (en) | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
DK1363876T3 (da) * | 2001-02-14 | 2009-11-30 | Karobio Ab | Glucocorticoidreceptormodulatorer |
US7405230B2 (en) * | 2002-07-19 | 2008-07-29 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs |
CA2492911A1 (en) | 2002-07-19 | 2004-01-29 | Memory Pharmaceuticals Corporation | 6-amino-1h-indazole and 4-aminobenzofuran compounds as phosphodiesterase 4 inhibitors |
EP1569908B1 (en) | 2002-11-19 | 2010-09-15 | Memory Pharmaceuticals Corporation | Pyridine n-oxide compounds as phosphodiesterase 4 inhibitors |
US20060040981A1 (en) * | 2002-11-22 | 2006-02-23 | Daniel Dube | Use of phosphodiesterase-4 inhibitors as enhancers of cognition |
MXPA05006463A (es) * | 2002-12-27 | 2005-08-26 | Lundbeck & Co As H | Derivados de 1,2,4-triaminobenceno, utiles para tratar transtornos del sistema nervioso central. |
FR2856595B1 (fr) * | 2003-06-27 | 2008-05-30 | Exonhit Therapeutics Sa | Methodes et compositions pour le traitement de deficits cognitifs. |
MXPA06002521A (es) | 2003-09-05 | 2006-06-20 | Altana Pharma Ag | Uso de inhibidores de pde4 para el tratamiento de diabetes mellitus. |
MY141255A (en) * | 2003-12-11 | 2010-03-31 | Memory Pharm Corp | Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs |
RU2392278C2 (ru) | 2004-07-15 | 2010-06-20 | Джапан Тобакко Инк. | Конденсированное производное бензамида и ингибитор активности подтипа 1 рецептора ваниллоида (vr1) |
US20070287716A1 (en) * | 2004-10-28 | 2007-12-13 | Hu Essa H | Pyrimidine and Quinoline Potentiators of Metabotropic Glutamate Receptors |
EA015382B1 (ru) | 2005-03-08 | 2011-08-30 | Никомед Гмбх | Применение рофлумиласта для лечения сахарного диабета типа 2 |
WO2006135828A2 (en) * | 2005-06-10 | 2006-12-21 | Memory Pharmaceuticals Corporation | Trisubstituted amines as phosphodiesterase 4 inhibitors |
AR057455A1 (es) * | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
US7906508B2 (en) | 2005-12-28 | 2011-03-15 | Japan Tobacco Inc. | 3,4-dihydrobenzoxazine compounds and inhibitors of vanilloid receptor subtype 1 (VRI) activity |
AU2008215948A1 (en) | 2007-02-12 | 2008-08-21 | Merck & Co., Inc. | Piperazine derivatives for treatment of AD and related conditions |
EP2110375A1 (en) * | 2008-04-14 | 2009-10-21 | CHIESI FARMACEUTICI S.p.A. | Phosphodiesterase-4 inhibitors belonging to the tertiary amine class |
EP2291181B9 (en) | 2008-04-18 | 2013-09-11 | University College Dublin National University Of Ireland, Dublin | Captodiamine for the treatment of depression symptoms |
WO2010041449A1 (ja) * | 2008-10-09 | 2010-04-15 | 国立大学法人 岡山大学 | Rxr作動性物質を有効成分とする抗アレルギー剤 |
MX2019008390A (es) * | 2009-06-12 | 2019-09-09 | Abivax | Compuestos utiles para tratar cancer. |
US10253020B2 (en) | 2009-06-12 | 2019-04-09 | Abivax | Compounds for preventing, inhibiting, or treating cancer, AIDS and/or premature aging |
KR101982461B1 (ko) | 2009-06-12 | 2019-05-24 | 아비박스 | 조기 노화, 구체적으로 조로증을 치료하는데 유용한 화합물 |
CA2789663C (en) | 2010-02-12 | 2018-10-02 | Raqualia Pharma Inc. | 5-ht4 receptor agonists for the treatment of dementia |
WO2013118855A1 (ja) | 2012-02-09 | 2013-08-15 | 塩野義製薬株式会社 | 複素環および炭素環誘導体 |
CN102603676B (zh) * | 2012-02-20 | 2014-02-12 | 徐江平 | 一种能避免呕吐反应的磷酸二酯酶4抑制剂 |
JP5959670B2 (ja) * | 2012-03-14 | 2016-08-02 | シノケム・コーポレーションSinochem Corporation | 抗腫瘍薬の調製における置換ジフェニルアミン化合物の使用 |
EP2757161A1 (en) | 2013-01-17 | 2014-07-23 | Splicos | miRNA-124 as a biomarker of viral infection |
HRP20211839T1 (hr) | 2013-07-05 | 2022-03-04 | Abivax | Biciklički spojevi korisni za liječenje bolesti uzrokovanih retrovirusima |
CA2921308A1 (en) | 2013-08-16 | 2015-02-19 | Universiteit Maastricht | Treatment of cognitive impairment with pde4 inhibitor |
EP2974729A1 (en) | 2014-07-17 | 2016-01-20 | Abivax | Quinoline derivatives for use in the treatment of inflammatory diseases |
EP3669873A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Quinoline derivatives for use ine the traeatment of inflammation diseases |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994027971A1 (en) | 1993-05-27 | 1994-12-08 | Smithkline Beecham Laboratoires Pharmaceutiques | Anti-arrhythmic n-substituted 3-benzazepines or isoquinolines |
WO1996021435A1 (en) | 1995-01-10 | 1996-07-18 | Euro-Celtique, S.A. | Compounds for and method of inhibiting phosphodiesterase iv |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07206789A (ja) * | 1993-09-01 | 1995-08-08 | Taisho Pharmaceut Co Ltd | コンブレタスタチン類縁化合物 |
FR2729142A1 (fr) * | 1995-01-06 | 1996-07-12 | Smithkline Beecham Lab | Nouvelles amines heterocycliques, leur procede de preparation et leur utilisation en tant que medicaments et notamment en tant qu'agents anti-arythmiques |
CA2295106C (en) * | 1997-06-24 | 2007-03-13 | Nikken Chemicals Co., Ltd. | 3-anilino-2-cycloalkenone derivatives |
WO2000071129A1 (en) * | 1999-05-21 | 2000-11-30 | Bristol-Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
DE50011851D1 (de) * | 1999-12-18 | 2006-01-19 | Wella Ag | 2-Aminoalkyl-1,4-diaminobenzol-Derivate und diese Verbindungen enthaltende Färbemittel |
-
2002
- 2002-01-22 CZ CZ20031986A patent/CZ20031986A3/cs unknown
- 2002-01-22 EE EEP200300347A patent/EE05362B1/xx not_active IP Right Cessation
- 2002-01-22 WO PCT/US2002/001508 patent/WO2002074726A2/en active Application Filing
- 2002-01-22 MX MXPA03006519A patent/MXPA03006519A/es active IP Right Grant
- 2002-01-22 CA CA002435847A patent/CA2435847A1/en not_active Abandoned
- 2002-01-22 AU AU2002303078A patent/AU2002303078B2/en not_active Ceased
- 2002-01-22 EP EP02731078A patent/EP1353907A2/en not_active Withdrawn
- 2002-01-22 NZ NZ527081A patent/NZ527081A/xx unknown
- 2002-01-22 HU HU0302793A patent/HUP0302793A3/hu unknown
- 2002-01-22 BR BR0206943-1A patent/BR0206943A/pt not_active Application Discontinuation
- 2002-01-22 PL PL02373301A patent/PL373301A1/xx not_active Application Discontinuation
- 2002-01-22 CN CNB028070100A patent/CN100378075C/zh not_active Expired - Fee Related
- 2002-01-22 JP JP2002573735A patent/JP4223287B2/ja not_active Expired - Fee Related
- 2002-01-22 IL IL15695802A patent/IL156958A0/xx unknown
- 2002-01-22 SK SK915-2003A patent/SK9152003A3/sk unknown
- 2002-01-22 KR KR1020037009624A patent/KR100856622B1/ko not_active IP Right Cessation
- 2002-01-22 YU YU57603A patent/YU57603A/sh unknown
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2003
- 2003-07-18 BG BG108003A patent/BG108003A/bg unknown
- 2003-07-21 ZA ZA2003/05623A patent/ZA200305623B/en unknown
- 2003-07-21 NO NO20033288A patent/NO329548B1/no not_active IP Right Cessation
- 2003-07-22 MA MA27246A patent/MA25996A1/fr unknown
- 2003-08-20 HR HR20030662A patent/HRP20030662A2/hr not_active Application Discontinuation
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2004
- 2004-05-20 CL CL200401165A patent/CL2004001165A1/es unknown
- 2004-11-17 HK HK04109061A patent/HK1066215A1/xx not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994027971A1 (en) | 1993-05-27 | 1994-12-08 | Smithkline Beecham Laboratoires Pharmaceutiques | Anti-arrhythmic n-substituted 3-benzazepines or isoquinolines |
WO1996021435A1 (en) | 1995-01-10 | 1996-07-18 | Euro-Celtique, S.A. | Compounds for and method of inhibiting phosphodiesterase iv |
Also Published As
Publication number | Publication date |
---|---|
BR0206943A (pt) | 2006-01-24 |
HRP20030662A2 (en) | 2005-06-30 |
CL2004001165A1 (es) | 2005-04-15 |
HUP0302793A2 (hu) | 2003-11-28 |
CA2435847A1 (en) | 2002-09-26 |
NZ527081A (en) | 2006-03-31 |
EP1353907A2 (en) | 2003-10-22 |
ZA200305623B (en) | 2005-01-26 |
EE200300347A (et) | 2003-12-15 |
PL373301A1 (en) | 2005-08-22 |
CN100378075C (zh) | 2008-04-02 |
YU57603A (sh) | 2006-08-17 |
CZ20031986A3 (cs) | 2003-12-17 |
IL156958A0 (en) | 2004-02-08 |
AU2002303078B2 (en) | 2007-08-30 |
EE05362B1 (et) | 2010-12-15 |
NO329548B1 (no) | 2010-11-08 |
KR20040064606A (ko) | 2004-07-19 |
SK9152003A3 (en) | 2004-04-06 |
WO2002074726A3 (en) | 2003-03-13 |
MA25996A1 (fr) | 2003-12-31 |
JP2005507365A (ja) | 2005-03-17 |
MXPA03006519A (es) | 2004-10-15 |
HUP0302793A3 (en) | 2006-01-30 |
BG108003A (bg) | 2004-09-30 |
WO2002074726A2 (en) | 2002-09-26 |
NO20033288L (no) | 2003-09-22 |
NO20033288D0 (no) | 2003-07-21 |
HK1066215A1 (en) | 2005-03-18 |
JP4223287B2 (ja) | 2009-02-12 |
CN1498211A (zh) | 2004-05-19 |
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