JP5100657B2 - グルカゴン受容体アンタゴニストおよびその製造及び治療用途 - Google Patents
グルカゴン受容体アンタゴニストおよびその製造及び治療用途 Download PDFInfo
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- JP5100657B2 JP5100657B2 JP2008541450A JP2008541450A JP5100657B2 JP 5100657 B2 JP5100657 B2 JP 5100657B2 JP 2008541450 A JP2008541450 A JP 2008541450A JP 2008541450 A JP2008541450 A JP 2008541450A JP 5100657 B2 JP5100657 B2 JP 5100657B2
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- Japan
- Prior art keywords
- group
- biphenyl
- benzoylamino
- halogens
- yloxymethyl
- 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.)
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- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 229940122904 Glucagon receptor antagonist Drugs 0.000 title abstract description 6
- 230000001225 therapeutic effect Effects 0.000 title description 3
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- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 125
- 150000002367 halogens Chemical class 0.000 claims description 110
- 239000001257 hydrogen Substances 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- -1 3,3-dimethylbutyl Chemical group 0.000 claims description 54
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 41
- 238000011282 treatment Methods 0.000 claims description 32
- 150000002431 hydrogen Chemical class 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical class N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
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- 125000001424 substituent group Chemical group 0.000 claims description 14
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 10
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- IVGUKGHYPQIEEZ-UHFFFAOYSA-N 3-[[4-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenoxy]-5,5,5-trifluoropentan-2-yl]benzoyl]amino]propanoic acid Chemical compound C=1C(C)=C(C=2C=CC(=CC=2)C(F)(F)F)C(C)=CC=1OCC(CCC(F)(F)F)C1=CC=C(C(=O)NCCC(O)=O)C=C1 IVGUKGHYPQIEEZ-UHFFFAOYSA-N 0.000 claims description 5
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- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 5
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- UTEBEYLRBKOJNN-UHFFFAOYSA-N 3-[[4-[4-[[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenoxy]methyl]hepta-1,6-dien-4-yl]benzoyl]amino]propanoic acid Chemical compound C=1C(C)=C(C=2C=CC(=CC=2)C(F)(F)F)C(C)=CC=1OCC(CC=C)(CC=C)C1=CC=C(C(=O)NCCC(O)=O)C=C1 UTEBEYLRBKOJNN-UHFFFAOYSA-N 0.000 claims description 4
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- NTOPXTVPTYQKDG-UHFFFAOYSA-N 3-[[4-[1-[[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenoxy]methyl]cyclopent-3-en-1-yl]benzoyl]amino]propanoic acid Chemical compound C=1C(C)=C(C=2C=CC(=CC=2)C(F)(F)F)C(C)=CC=1OCC1(C=2C=CC(=CC=2)C(=O)NCCC(O)=O)CC=CC1 NTOPXTVPTYQKDG-UHFFFAOYSA-N 0.000 claims description 3
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- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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- 125000000439 4-methylpentoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
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- 208000011580 syndromic disease Diseases 0.000 description 1
- 229960001693 terazosin Drugs 0.000 description 1
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 229960001130 urapidil Drugs 0.000 description 1
- 239000000777 urocortin Substances 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
-
- 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
-
- 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
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- 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
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73797905P | 2005-11-18 | 2005-11-18 | |
| US60/737,979 | 2005-11-18 | ||
| PCT/US2006/060769 WO2007114855A2 (en) | 2005-11-18 | 2006-11-10 | Glucagon receptor antagonists, preparation and therapeutic uses |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009519227A JP2009519227A (ja) | 2009-05-14 |
| JP2009519227A5 JP2009519227A5 (enExample) | 2009-12-10 |
| JP5100657B2 true JP5100657B2 (ja) | 2012-12-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2008541450A Expired - Fee Related JP5100657B2 (ja) | 2005-11-18 | 2006-11-10 | グルカゴン受容体アンタゴニストおよびその製造及び治療用途 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8076374B2 (enExample) |
| JP (1) | JP5100657B2 (enExample) |
| CN (1) | CN101309894B (enExample) |
| AT (1) | ATE473961T1 (enExample) |
| AU (1) | AU2006341392B2 (enExample) |
| BR (1) | BRPI0618484A2 (enExample) |
| CA (1) | CA2629321C (enExample) |
| DE (1) | DE602006015509D1 (enExample) |
| DK (1) | DK1951659T3 (enExample) |
| ES (1) | ES2346246T3 (enExample) |
| PT (1) | PT1951659E (enExample) |
| WO (1) | WO2007114855A2 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1758853T3 (da) * | 2004-06-14 | 2010-04-06 | Lilly Co Eli | Glucagon-receptorantagonister, fremstilling og terapeutiske anvendelser |
| KR20170085615A (ko) | 2007-02-09 | 2017-07-24 | 메타베이시스 테라퓨틱스, 인크. | 글루카곤 수용체의 길항제 |
| EP2799428B1 (en) | 2008-08-13 | 2016-11-16 | Metabasis Therapeutics, Inc. | Glucagon antagonists |
| AR073412A1 (es) | 2008-10-03 | 2010-11-03 | Schering Corp | Derivados de espiro imidazolona como antagonistas del receptor glucagon y composiciones que los comprende. |
| WO2011037815A1 (en) | 2009-09-22 | 2011-03-31 | Schering Corporation | Novel pyrrolidines as glucagon receptor antagonists, compositions, and methods for their use |
| JP5694561B2 (ja) | 2010-12-23 | 2015-04-01 | ファイザー・インク | グルカゴン受容体モジュレーター |
| WO2012107850A1 (en) | 2011-02-08 | 2012-08-16 | Pfizer Inc. | Glucagon receptor modulator |
| KR20140023441A (ko) | 2011-07-22 | 2014-02-26 | 화이자 인코포레이티드 | 퀴놀린일 글루카곤 수용체 조절제 |
| WO2015066252A1 (en) | 2013-11-04 | 2015-05-07 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions thereof, and methods of use |
| EP3154956A4 (en) | 2014-06-12 | 2018-01-17 | Ligand Pharmaceuticals, Inc. | Glucagon antagonists |
| US10201617B2 (en) | 2014-10-24 | 2019-02-12 | Zhuhai Beihai Biotech Co., Ltd. | 3-substituted piperidine-2, 6-diones and non-covalent complexes with albumin |
| CN111954560A (zh) | 2018-02-13 | 2020-11-17 | 配体药物公司 | 胰高血糖素受体拮抗剂 |
| CN110143935B (zh) * | 2019-06-03 | 2022-09-30 | 华侨大学 | 一种2，5-二取代呋喃衍生物的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9420557D0 (en) * | 1994-10-12 | 1994-11-30 | Zeneca Ltd | Aromatic compounds |
| NL1004346C2 (nl) | 1996-10-23 | 1998-04-24 | Dsm Nv | Werkwijze voor het scheiden van een mengsel van enantiomeren in een geschikt oplosmiddel. |
| EP1463715A1 (en) | 2001-12-03 | 2004-10-06 | Novo Nordisk A/S | Novel glucagon antagonists |
| WO2004002480A1 (en) | 2002-06-27 | 2004-01-08 | Novo Nordisk A/S | Novel glucagon antagonists/inverse agonists |
| AU2003291959A1 (en) * | 2002-12-20 | 2004-07-14 | Novo Nordisk A/S | Novel glucagon antagonists |
| WO2004063147A1 (en) * | 2003-01-10 | 2004-07-29 | Novo Nordisk A/S | Salts and solvates of glucagon antagonists |
| WO2005102067A1 (en) | 2004-04-26 | 2005-11-03 | Ipn Ip B.V. | Packaged flowable ice product, such as a milk shake |
-
2006
- 2006-11-10 BR BRPI0618484-7A patent/BRPI0618484A2/pt not_active IP Right Cessation
- 2006-11-10 AT AT06850138T patent/ATE473961T1/de active
- 2006-11-10 ES ES06850138T patent/ES2346246T3/es active Active
- 2006-11-10 DK DK06850138.6T patent/DK1951659T3/da active
- 2006-11-10 PT PT06850138T patent/PT1951659E/pt unknown
- 2006-11-10 DE DE602006015509T patent/DE602006015509D1/de active Active
- 2006-11-10 CA CA2629321A patent/CA2629321C/en not_active Expired - Fee Related
- 2006-11-10 CN CN2006800428747A patent/CN101309894B/zh not_active Expired - Fee Related
- 2006-11-10 JP JP2008541450A patent/JP5100657B2/ja not_active Expired - Fee Related
- 2006-11-10 US US12/093,598 patent/US8076374B2/en not_active Expired - Fee Related
- 2006-11-10 AU AU2006341392A patent/AU2006341392B2/en not_active Ceased
- 2006-11-10 WO PCT/US2006/060769 patent/WO2007114855A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CN101309894A (zh) | 2008-11-19 |
| CA2629321C (en) | 2013-08-06 |
| CA2629321A1 (en) | 2007-10-11 |
| AU2006341392A1 (en) | 2007-10-11 |
| CN101309894B (zh) | 2012-10-03 |
| JP2009519227A (ja) | 2009-05-14 |
| PT1951659E (pt) | 2010-09-10 |
| AU2006341392B2 (en) | 2012-05-17 |
| ATE473961T1 (de) | 2010-07-15 |
| ES2346246T3 (es) | 2010-10-13 |
| DE602006015509D1 (de) | 2010-08-26 |
| US20080319074A1 (en) | 2008-12-25 |
| US8076374B2 (en) | 2011-12-13 |
| WO2007114855A2 (en) | 2007-10-11 |
| WO2007114855A3 (en) | 2007-11-29 |
| DK1951659T3 (da) | 2010-10-11 |
| BRPI0618484A2 (pt) | 2011-08-30 |
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