JP6474804B2 - アザベンゾイミダゾール誘導体 - Google Patents
アザベンゾイミダゾール誘導体 Download PDFInfo
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- JP6474804B2 JP6474804B2 JP2016527342A JP2016527342A JP6474804B2 JP 6474804 B2 JP6474804 B2 JP 6474804B2 JP 2016527342 A JP2016527342 A JP 2016527342A JP 2016527342 A JP2016527342 A JP 2016527342A JP 6474804 B2 JP6474804 B2 JP 6474804B2
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- Japan
- Prior art keywords
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- imidazo
- chloro
- phenyl
- yloxy
- Prior art date
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- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical class C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 title description 5
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- 150000003839 salts Chemical class 0.000 claims description 38
- 108010011376 AMP-Activated Protein Kinases Proteins 0.000 claims description 33
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- 239000003814 drug Substances 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 229940124597 therapeutic agent Drugs 0.000 claims description 20
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 208000024891 symptom Diseases 0.000 claims description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 18
- 206010012601 diabetes mellitus Diseases 0.000 claims description 16
- 208000008589 Obesity Diseases 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 235000020824 obesity Nutrition 0.000 claims description 14
- 208000030159 metabolic disease Diseases 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 10
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 206010022489 Insulin Resistance Diseases 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000016097 disease of metabolism Diseases 0.000 claims description 4
- 206010033307 Overweight Diseases 0.000 claims description 3
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
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- 239000000460 chlorine Substances 0.000 description 46
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 26
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- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 22
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- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
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- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 13
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- 125000000217 alkyl group Chemical group 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
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- AUELWJRRASQDKI-UHFFFAOYSA-N cyclohexyl carbamate Chemical compound NC(=O)OC1CCCCC1 AUELWJRRASQDKI-UHFFFAOYSA-N 0.000 description 10
- KOGOBKOHQTZGIS-UHFFFAOYSA-N cyclohexyl methanesulfonate Chemical compound CS(=O)(=O)OC1CCCCC1 KOGOBKOHQTZGIS-UHFFFAOYSA-N 0.000 description 10
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- 125000001072 heteroaryl group Chemical group 0.000 description 10
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
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Classifications
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- 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
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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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13191195.0 | 2013-10-31 | ||
| EP13191195 | 2013-10-31 | ||
| PCT/EP2014/072959 WO2015063011A1 (en) | 2013-10-31 | 2014-10-27 | Azabenzimidazole derivatives |
Publications (3)
| Publication Number | Publication Date |
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| JP2016535049A JP2016535049A (ja) | 2016-11-10 |
| JP2016535049A5 JP2016535049A5 (enExample) | 2017-12-14 |
| JP6474804B2 true JP6474804B2 (ja) | 2019-02-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2016527342A Active JP6474804B2 (ja) | 2013-10-31 | 2014-10-27 | アザベンゾイミダゾール誘導体 |
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| Country | Link |
|---|---|
| US (1) | US9187477B2 (enExample) |
| EP (1) | EP3063148B1 (enExample) |
| JP (1) | JP6474804B2 (enExample) |
| WO (1) | WO2015063011A1 (enExample) |
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| AU2015309863B2 (en) | 2014-08-27 | 2019-12-05 | Shionogi & Co., Ltd. | Azaindole derivative having AMPK-activating effect |
| KR20170077131A (ko) | 2014-10-28 | 2017-07-05 | 시오노기세야쿠 가부시키가이샤 | Ampk 활성화 작용을 갖는 복소환 유도체 |
| JPWO2017146186A1 (ja) | 2016-02-26 | 2018-12-20 | 塩野義製薬株式会社 | Ａｍｐｋ活性化作用を有する５−フェニルアザインドール誘導体 |
| CN109476661A (zh) * | 2016-05-20 | 2019-03-15 | 盐野义制药株式会社 | 具有ampk活化作用的5-取代苯并咪唑及5-取代氮杂苯并咪唑衍生物 |
| JP2023526625A (ja) | 2020-05-19 | 2023-06-22 | キャリーオペ，インク． | Ａｍｐｋアクチベーター |
| CN116390925A (zh) | 2020-06-26 | 2023-07-04 | 卡尔优普公司 | Ampk活化剂 |
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| PH12013501686A1 (en) * | 2011-02-25 | 2017-10-25 | Merck Sharp & Dohme | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| EP2733141B1 (en) * | 2011-07-15 | 2019-01-09 | Shionogi & Co., Ltd. | Azabenzimidazole derivative having ampk-activating activity |
| WO2014031465A1 (en) * | 2012-08-22 | 2014-02-27 | Merck Sharp & Dohme Corp. | Novel azabenzimidazole tetrahydropyran derivatives |
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| EP3063148A1 (en) | 2016-09-07 |
| US20150119393A1 (en) | 2015-04-30 |
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