JP2008526818A - Ｐｄｅ１０インヒビターとしての新規のピロロジヒドロイソキノリン - Google Patents
Ｐｄｅ１０インヒビターとしての新規のピロロジヒドロイソキノリン Download PDFInfo
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- JP2008526818A JP2008526818A JP2007549915A JP2007549915A JP2008526818A JP 2008526818 A JP2008526818 A JP 2008526818A JP 2007549915 A JP2007549915 A JP 2007549915A JP 2007549915 A JP2007549915 A JP 2007549915A JP 2008526818 A JP2008526818 A JP 2008526818A
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- alkyl
- alkoxy
- hydrogen
- phenyl
- substituted
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- 239000003112 inhibitor Substances 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 259
- 229910052739 hydrogen Inorganic materials 0.000 claims description 148
- 239000001257 hydrogen Substances 0.000 claims description 148
- -1 nitro, amino Chemical group 0.000 claims description 137
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 57
- 150000002367 halogens Chemical group 0.000 claims description 57
- HBMUMVMGBLMQJT-UHFFFAOYSA-N pyrrolo[2,1-a]isoquinoline Chemical group C12=CC=CC=C2C=CN2C1=CC=C2 HBMUMVMGBLMQJT-UHFFFAOYSA-N 0.000 claims description 54
- 150000002431 hydrogen Chemical group 0.000 claims description 53
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
- 229910052731 fluorine Inorganic materials 0.000 claims description 43
- 239000011737 fluorine Substances 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 33
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- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 29
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
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- 229910052717 sulfur Chemical group 0.000 claims description 24
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- 125000005842 heteroatom Chemical group 0.000 claims description 23
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- 239000001301 oxygen Chemical group 0.000 claims description 23
- 239000011593 sulfur Chemical group 0.000 claims description 23
- 125000002950 monocyclic group Chemical group 0.000 claims description 22
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- 125000003118 aryl group Chemical group 0.000 claims description 19
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- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
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- 125000001424 substituent group Chemical group 0.000 claims description 12
- URBDWHWYNSSOST-UHFFFAOYSA-N C1=CNC=C2C3=CC=NC3=CC=C21 Chemical group C1=CNC=C2C3=CC=NC3=CC=C21 URBDWHWYNSSOST-UHFFFAOYSA-N 0.000 claims description 11
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- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 6
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- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims description 3
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- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 230000003647 oxidation Effects 0.000 description 1
- 230000021962 pH elevation Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
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- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
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- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
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- 235000020989 red meat Nutrition 0.000 description 1
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- 208000017520 skin disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Chemical class 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
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- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
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- 230000009885 systemic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
- 239000010936 titanium Chemical class 0.000 description 1
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- 230000001256 tonic effect Effects 0.000 description 1
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
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- DJXRIQMCROIRCZ-XOEOCAAJSA-N vibegron Chemical compound C1([C@H]([C@@H]2N[C@H](CC=3C=CC(NC(=O)[C@H]4N5C(=O)C=CN=C5CC4)=CC=3)CC2)O)=CC=CC=C1 DJXRIQMCROIRCZ-XOEOCAAJSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Addiction (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05100154 | 2005-01-12 | ||
| PCT/EP2006/050167 WO2006089815A1 (en) | 2005-01-12 | 2006-01-11 | Novel pyrrolodihydroisoquinolines as pde10 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008526818A true JP2008526818A (ja) | 2008-07-24 |
| JP2008526818A5 JP2008526818A5 (enExample) | 2009-03-05 |
Family
ID=36097003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007549915A Withdrawn JP2008526818A (ja) | 2005-01-12 | 2006-01-11 | Ｐｄｅ１０インヒビターとしての新規のピロロジヒドロイソキノリン |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20080161338A1 (enExample) |
| EP (1) | EP1838707B1 (enExample) |
| JP (1) | JP2008526818A (enExample) |
| AT (1) | ATE430148T1 (enExample) |
| AU (1) | AU2006218054A1 (enExample) |
| CA (1) | CA2593750A1 (enExample) |
| DE (1) | DE602006006544D1 (enExample) |
| ES (1) | ES2326337T3 (enExample) |
| WO (1) | WO2006089815A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200510407A (en) * | 2003-06-30 | 2005-03-16 | Altana Pharma Ag | Novel pyrrolodihydroisoquinolines as PDE 10 inhibitors |
| EP1838708A2 (en) * | 2005-01-12 | 2007-10-03 | Nycomed GmbH | Pyrrolodihydroisoquinolines as antiproliferative agents |
| US7875618B2 (en) * | 2007-11-30 | 2011-01-25 | Wyeth | Substituted imidazo[1,5-a]quinoxalines useful as inhibitors of phosphodiesterase 10 for the treatment of neurological and other disorders |
| WO2009070583A1 (en) * | 2007-11-30 | 2009-06-04 | Wyeth | Pyrido[3,2-e]pyrazines, process for preparing the same, and their use as inhibitors of phosphodiesterase 10 |
| TW200944523A (en) | 2008-02-08 | 2009-11-01 | Organon Nv | (Dihydro)pyrrolo[2,1-a]isoquinolines |
| SG192839A1 (en) | 2011-02-18 | 2013-09-30 | Allergan Inc | Substituted 6,7-dialkoxy-3-isoquinolinol derivatives as inhibitors of phosphodiesterase 10 (pde10a) |
| GB201117453D0 (en) * | 2011-10-10 | 2011-11-23 | Univ Dundee | Improved sperm function/activity |
| WO2014071044A1 (en) | 2012-11-01 | 2014-05-08 | Allergan, Inc. | Substituted 6,7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (pde10a) |
| US9200016B2 (en) | 2013-12-05 | 2015-12-01 | Allergan, Inc. | Substituted 6, 7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (PDE 10A) |
| CN119367368B (zh) * | 2024-11-28 | 2025-12-05 | 中山大学 | 氮杂四元环连接的吡唑并吡啶类化合物在制备治疗肺动脉高压的药物中的应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2761358B1 (fr) * | 1997-03-27 | 1999-05-07 | Adir | Nouveaux composes de n-aryl piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US6930114B2 (en) * | 2000-12-13 | 2005-08-16 | Bayer Pharmaceuticals Corporation | Pyrrolo (2.1a)dihydroisoquinolines and their use as phosphodiesterase 10a inhibitors |
| US20030032579A1 (en) * | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| IL149106A0 (en) * | 2001-04-20 | 2002-11-10 | Pfizer Prod Inc | Therapeutic use of selective pde10 inhibitors |
| US20030018047A1 (en) * | 2001-04-20 | 2003-01-23 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| WO2003014115A1 (en) * | 2001-08-06 | 2003-02-20 | Bayer Aktiengesellschaft | 3-substituted pyrrolo (2.1-a) isoquinoline derivatives |
| AU2002366362A1 (en) * | 2001-12-18 | 2003-06-30 | Bayer Aktiengesellschaft | 2-substituted pyrrolo(2.1-a)isoquinolines against cancer |
| TW200510407A (en) * | 2003-06-30 | 2005-03-16 | Altana Pharma Ag | Novel pyrrolodihydroisoquinolines as PDE 10 inhibitors |
-
2006
- 2006-01-11 EP EP06701124A patent/EP1838707B1/en active Active
- 2006-01-11 CA CA002593750A patent/CA2593750A1/en not_active Abandoned
- 2006-01-11 WO PCT/EP2006/050167 patent/WO2006089815A1/en not_active Ceased
- 2006-01-11 DE DE602006006544T patent/DE602006006544D1/de active Active
- 2006-01-11 AT AT06701124T patent/ATE430148T1/de not_active IP Right Cessation
- 2006-01-11 JP JP2007549915A patent/JP2008526818A/ja not_active Withdrawn
- 2006-01-11 AU AU2006218054A patent/AU2006218054A1/en not_active Abandoned
- 2006-01-11 ES ES06701124T patent/ES2326337T3/es active Active
- 2006-01-11 US US11/794,497 patent/US20080161338A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006218054A1 (en) | 2006-08-31 |
| ATE430148T1 (de) | 2009-05-15 |
| EP1838707B1 (en) | 2009-04-29 |
| US20080161338A1 (en) | 2008-07-03 |
| ES2326337T3 (es) | 2009-10-07 |
| EP1838707A1 (en) | 2007-10-03 |
| CA2593750A1 (en) | 2006-08-31 |
| DE602006006544D1 (de) | 2009-06-10 |
| WO2006089815A1 (en) | 2006-08-31 |
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