EA027082B1 - Производные имидазола в качестве ингибиторов фермента pde10a - Google Patents
Производные имидазола в качестве ингибиторов фермента pde10a Download PDFInfo
- Publication number
- EA027082B1 EA027082B1 EA201390741A EA201390741A EA027082B1 EA 027082 B1 EA027082 B1 EA 027082B1 EA 201390741 A EA201390741 A EA 201390741A EA 201390741 A EA201390741 A EA 201390741A EA 027082 B1 EA027082 B1 EA 027082B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- triazolo
- imidazo
- dimethyl
- pyrazin
- isoindole
- Prior art date
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- 239000002532 enzyme inhibitor Substances 0.000 title abstract 2
- 150000002460 imidazoles Chemical class 0.000 title 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title 1
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
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- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 6
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 5
- -1 [1,2,4] triazolo [1,5-a] pyridinyl Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 21
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- DBMVTWOKPCPULJ-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-5h-imidazo[2,1-a]isoindole Chemical compound C1=CC=C2C3=NC(CCC=4N=C5C(C)=NC=C(N5N=4)C)=CN3CC2=C1 DBMVTWOKPCPULJ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052805 deuterium Inorganic materials 0.000 claims description 5
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- DVCBKKQNCIKRPU-UHFFFAOYSA-N [2-[2-(5h-imidazo[2,1-a]isoindol-2-yl)ethyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]methanol Chemical compound C1=CC=C2C3=NC(CCC=4N=C5C(CO)=NC=C(N5N=4)C)=CN3CC2=C1 DVCBKKQNCIKRPU-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 208000022610 schizoaffective disease Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 210000005250 spinal neuron Anatomy 0.000 description 1
- 238000011064 split stream procedure Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001300 stimulation of adenylate cyclase Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 150000005075 thioxanthenes Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- KTSWILXIWHVQLR-UHFFFAOYSA-N tributylgermane Chemical compound CCCC[GeH](CCCC)CCCC KTSWILXIWHVQLR-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- AVCVDUDESCZFHJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound [Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 AVCVDUDESCZFHJ-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- WFPIAZLQTJBIFN-DVZOWYKESA-N zuclopenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(Cl)=CC=C2SC2=CC=CC=C2/1 WFPIAZLQTJBIFN-DVZOWYKESA-N 0.000 description 1
- 229960004141 zuclopenthixol Drugs 0.000 description 1
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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
-
- 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
-
- 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
- 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
- A61P25/24—Antidepressants
-
- 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
-
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Psychology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA201001045 | 2010-11-19 | ||
| PCT/DK2011/000136 WO2012065612A1 (en) | 2010-11-19 | 2011-11-18 | Imidazole derivatives as pde10a enzyme inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201390741A1 EA201390741A1 (ru) | 2013-11-29 |
| EA027082B1 true EA027082B1 (ru) | 2017-06-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201390741A EA027082B1 (ru) | 2010-11-19 | 2011-11-18 | Производные имидазола в качестве ингибиторов фермента pde10a |
Country Status (32)
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8552045B2 (en) | 2010-11-19 | 2013-10-08 | H. Lundbeck A/S | Tricyclic imidazole compounds as PDE10 inhibitors |
| JP6106603B2 (ja) * | 2011-01-11 | 2017-04-05 | スノビオン プハルマセウトイカルス インコーポレイテッド | ヘテロアリール化合物及びその使用方法 |
| WO2013045607A1 (en) * | 2011-09-30 | 2013-04-04 | H. Lundbeck A/S | Quinazoline linked heteroaromatic tricycle derivatives as pde10a enzyme inhibitors |
| WO2013107856A1 (en) * | 2012-01-20 | 2013-07-25 | H. Lundbeck A/S | Imidazole derivatives as pde10a enzyme inhibitors |
| WO2013192273A1 (en) * | 2012-06-19 | 2013-12-27 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
| CN103435617B (zh) * | 2013-08-22 | 2016-04-27 | 南京华安药业有限公司 | 一种6,7-二氢-5H-吡咯并[1,2-a]咪唑-2-甲醛的合成方法 |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| TWI729109B (zh) | 2016-04-12 | 2021-06-01 | 丹麥商Ｈ 朗德貝克公司 | 作爲PDE1抑制劑的1,5-二氫-4H-吡唑并[3,4-d]嘧啶-4-酮和1,5-二氫-4H-吡唑并[4,3-c]吡啶-4-酮 |
| US10633382B2 (en) | 2016-10-18 | 2020-04-28 | H. Lundbeck A/S | Imidazopyrazinones, pyrazolopyrimidinones and pyrazolopyridinones as PDE1 inhibitors |
| LT3532064T (lt) | 2016-10-28 | 2020-09-25 | H. Lundbeck A/S | Kompleksiniai gydymai, apimantys imidazopirazonus, skirti psichiatrinių ir (arba) kognityvinių sutrikimų gydymui |
| RU2019108717A (ru) | 2016-10-28 | 2020-11-30 | Х. Лундбекк А/С | Комбинированные средства для лечения, предусматривающего введение имидазопиразинонов |
| WO2020094591A1 (en) | 2018-11-06 | 2020-05-14 | H. Lundbeck A/S | Pde10a inhibitors for treating negative symptoms and cognitive impairments in a patient suffering from schizophrenia |
| CN109776527A (zh) * | 2019-02-21 | 2019-05-21 | 药雅科技(上海)有限公司 | 一种5-溴-7-氮杂吲哚的合成方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009152825A1 (en) * | 2008-06-20 | 2009-12-23 | H. Lundbeck A/S | Novel phenylimidazole derivatives as pde10a enzyme inhibitors |
| WO2010145668A1 (en) * | 2009-06-19 | 2010-12-23 | H. Lundbeck A/S | Novel phenylimidazole derivative as pde10a enzyme inhibitor |
| WO2011072695A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Phenylimidazole derivatives comprising an ethynylene linker as pde10a enzyme inhibitors |
| WO2011072694A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Heteroaromatic phenylimidazole derivatives as pde10a enzyme inhibitors |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8307865D0 (en) | 1983-03-22 | 1983-04-27 | Fujisawa Pharmaceutical Co | Benzimidazole derivatives |
| US5571775A (en) | 1994-07-11 | 1996-11-05 | Dowelanco | N-aryl[1,2,4]triazolo[1,5-a]pyridine-2-sulfonamide herbicides |
| IL149106A0 (en) | 2001-04-20 | 2002-11-10 | Pfizer Prod Inc | Therapeutic use of selective pde10 inhibitors |
| US20030032579A1 (en) | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| EP1641457B1 (en) | 2003-06-30 | 2009-08-05 | Nycomed GmbH | Pyrrolo-dihydroisoquinoline derivatives as pde10 inhibitors |
| MXPA05013553A (es) | 2003-06-30 | 2006-03-09 | Altana Pharma Ag | Pirrolodihidroisoquinolinas como inhibidores de pde10. |
| EP1651251A4 (en) | 2003-07-31 | 2008-06-18 | Bayer Pharmaceuticals Corp | METHOD FOR THE TREATMENT OF DIABETES AND RELATED DISEASES USING PDE 10A INHIBITORS |
| EP1723134A2 (en) | 2004-02-18 | 2006-11-22 | Pfizer Products Incorporated | Tetrahydroisoquinolinyl derivatives of quinazoline and isoquinoline |
| BRPI0511854A (pt) | 2004-06-07 | 2008-01-15 | Pfizer Prod Inc | inibição de fosfodiestearase 10 como tratamento para condições relacionados com a obesidade e relacionadas a sìndrome metabólica |
| US20060019975A1 (en) | 2004-07-23 | 2006-01-26 | Pfizer Inc | Novel piperidyl derivatives of quinazoline and isoquinoline |
| CA2578996A1 (en) | 2004-09-03 | 2006-03-16 | Memory Pharmaceuticals Corporation | 4-substituted 4, 6-dialkoxy-cinnoline derivatives as phospodiesterase 10 inhibitors for the treatment of psychiatric or neurological syndroms |
| US8133897B2 (en) * | 2008-06-20 | 2012-03-13 | H. Lundbeck A/S | Phenylimidazole derivatives as PDE10A enzyme inhibitors |
| TWI481607B (zh) * | 2009-12-17 | 2015-04-21 | Lundbeck & Co As H | 作為ｐｄｅ１０ａ酵素抑制劑的２－芳基咪唑衍生物 |
-
2011
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- 2011-11-18 PE PE2013001212A patent/PE20141534A1/es active IP Right Grant
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- 2011-11-18 EA EA201390741A patent/EA027082B1/ru not_active IP Right Cessation
- 2011-11-18 AR ARP110104313A patent/AR083926A1/es unknown
- 2011-11-18 AU AU2011331607A patent/AU2011331607B2/en not_active Ceased
- 2011-11-18 CN CN201180065325.2A patent/CN103328487B/zh not_active Expired - Fee Related
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- 2011-11-18 UA UAA201307630A patent/UA112065C2/uk unknown
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- 2011-11-18 RS RS20150574A patent/RS54210B1/sr unknown
- 2011-11-18 ES ES11793325.9T patent/ES2547090T3/es active Active
- 2011-11-18 PH PH1/2013/500968A patent/PH12013500968A1/en unknown
- 2011-11-18 AP AP2013006928A patent/AP3342A/xx active
- 2011-11-18 KR KR1020137012797A patent/KR101916487B1/ko not_active Expired - Fee Related
- 2011-11-18 CA CA2817663A patent/CA2817663C/en not_active Expired - Fee Related
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- 2011-11-18 PL PL11793325T patent/PL2640731T3/pl unknown
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- 2011-11-18 EP EP11793325.9A patent/EP2640731B9/en active Active
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- 2011-11-18 JP JP2013539140A patent/JP5937608B2/ja not_active Expired - Fee Related
- 2011-11-18 WO PCT/DK2011/000136 patent/WO2012065612A1/en not_active Ceased
- 2011-11-18 HU HUE11793325A patent/HUE025596T2/en unknown
- 2011-11-18 PT PT117933259T patent/PT2640731E/pt unknown
-
2013
- 2013-05-16 GT GT201300130A patent/GT201300130A/es unknown
- 2013-05-16 CR CR20130226A patent/CR20130226A/es unknown
- 2013-05-17 ZA ZA2013/03607A patent/ZA201303607B/en unknown
- 2013-06-18 EC ECSP13012698 patent/ECSP13012698A/es unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009152825A1 (en) * | 2008-06-20 | 2009-12-23 | H. Lundbeck A/S | Novel phenylimidazole derivatives as pde10a enzyme inhibitors |
| WO2010145668A1 (en) * | 2009-06-19 | 2010-12-23 | H. Lundbeck A/S | Novel phenylimidazole derivative as pde10a enzyme inhibitor |
| WO2011072695A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Phenylimidazole derivatives comprising an ethynylene linker as pde10a enzyme inhibitors |
| WO2011072694A1 (en) * | 2009-12-17 | 2011-06-23 | H. Lundbeck A/S | Heteroaromatic phenylimidazole derivatives as pde10a enzyme inhibitors |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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