JP4332433B2 - Ccr−3レセプターアンタゴニストとしてのアゼチジン誘導体 - Google Patents
Ccr−3レセプターアンタゴニストとしてのアゼチジン誘導体 Download PDFInfo
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- JP4332433B2 JP4332433B2 JP2003575960A JP2003575960A JP4332433B2 JP 4332433 B2 JP4332433 B2 JP 4332433B2 JP 2003575960 A JP2003575960 A JP 2003575960A JP 2003575960 A JP2003575960 A JP 2003575960A JP 4332433 B2 JP4332433 B2 JP 4332433B2
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- Prior art keywords
- alkyl
- phenoxy
- azetidin
- phenyl
- substituted
- 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.)
- Expired - Fee Related
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- 108010017316 CCR3 Receptors Proteins 0.000 title description 3
- 102000004499 CCR3 Receptors Human genes 0.000 title description 3
- 229940044551 receptor antagonist Drugs 0.000 title description 2
- 239000002464 receptor antagonist Substances 0.000 title description 2
- 150000001539 azetidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 168
- -1 phenoxy oxy Chemical group 0.000 claims description 153
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 75
- 239000001257 hydrogen Substances 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 125000001424 substituent group Chemical group 0.000 claims description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 125000000623 heterocyclic group Chemical class 0.000 claims description 34
- 150000003839 salts Chemical group 0.000 claims description 34
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- 125000001624 naphthyl group Chemical group 0.000 claims description 32
- 239000001301 oxygen Chemical group 0.000 claims description 30
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 29
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
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- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 229910052717 sulfur Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 239000011593 sulfur Chemical group 0.000 claims description 19
- 125000006413 ring segment Chemical group 0.000 claims description 18
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000004423 acyloxy group Chemical group 0.000 claims description 12
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- ZXVYOESVEWVQDR-UHFFFAOYSA-N phenyl n-[3-(dimethylcarbamoyl)phenyl]carbamate Chemical compound CN(C)C(=O)C1=CC=CC(NC(=O)OC=2C=CC=CC=2)=C1 ZXVYOESVEWVQDR-UHFFFAOYSA-N 0.000 description 1
- DNYPKBUXFIRXPO-UHFFFAOYSA-N phenyl n-[3-(methylcarbamoyl)phenyl]carbamate Chemical compound CNC(=O)C1=CC=CC(NC(=O)OC=2C=CC=CC=2)=C1 DNYPKBUXFIRXPO-UHFFFAOYSA-N 0.000 description 1
- YMYXABQKRCYYJB-UHFFFAOYSA-N phenyl n-[4-(methoxymethyl)phenyl]carbamate Chemical compound C1=CC(COC)=CC=C1NC(=O)OC1=CC=CC=C1 YMYXABQKRCYYJB-UHFFFAOYSA-N 0.000 description 1
- UQJHSJZRRHVSTK-UHFFFAOYSA-N phenyl n-[4-[acetyl(methyl)amino]phenyl]carbamate Chemical compound C1=CC(N(C(C)=O)C)=CC=C1NC(=O)OC1=CC=CC=C1 UQJHSJZRRHVSTK-UHFFFAOYSA-N 0.000 description 1
- ZBELOBHZQGHUNR-UHFFFAOYSA-N phenyl n-pyridin-3-ylcarbamate Chemical compound C=1C=CC=CC=1OC(=O)NC1=CC=CN=C1 ZBELOBHZQGHUNR-UHFFFAOYSA-N 0.000 description 1
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- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- HNUSZIQSLZBZTO-UHFFFAOYSA-N quinoline-3-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CN=C21 HNUSZIQSLZBZTO-UHFFFAOYSA-N 0.000 description 1
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- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
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- ROMQMQRPRNOOOF-UHFFFAOYSA-N tert-butyl 3-(4-chlorobenzoyl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1C(=O)C1=CC=C(Cl)C=C1 ROMQMQRPRNOOOF-UHFFFAOYSA-N 0.000 description 1
- WMCYWTMASDHKLR-UHFFFAOYSA-N tert-butyl 3-[(4-chlorophenyl)methyl]azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1CC1=CC=C(Cl)C=C1 WMCYWTMASDHKLR-UHFFFAOYSA-N 0.000 description 1
- YYJIKNGZPNMDBJ-NRFANRHFSA-N tert-butyl N-[(2S)-1-tert-butylsilyloxy-4-iodo-1,1-diphenylbutan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@@H](CCI)C(O[SiH2]C(C)(C)C)(C1=CC=CC=C1)C1=CC=CC=C1)=O YYJIKNGZPNMDBJ-NRFANRHFSA-N 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-N tert-butyl hydrogen carbonate Chemical compound CC(C)(C)OC(O)=O XKXIQBVKMABYQJ-UHFFFAOYSA-N 0.000 description 1
- XKQZGOQUIRSASV-CYBMUJFWSA-N tert-butyl n-[(2r)-4-[3-(4-chlorophenoxy)azetidin-1-yl]butan-2-yl]carbamate Chemical compound C1N(CC[C@@H](C)NC(=O)OC(C)(C)C)CC1OC1=CC=C(Cl)C=C1 XKQZGOQUIRSASV-CYBMUJFWSA-N 0.000 description 1
- UIMDTLOXOIDRDY-SSDOTTSWSA-N tert-butyl n-[(2r)-4-iodobutan-2-yl]carbamate Chemical compound ICC[C@@H](C)NC(=O)OC(C)(C)C UIMDTLOXOIDRDY-SSDOTTSWSA-N 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
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- 230000009385 viral infection Effects 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| GB0229627A GB0229627D0 (en) | 2002-12-19 | 2002-12-19 | Organic compounds |
| PCT/EP2003/002715 WO2003077907A1 (en) | 2002-03-15 | 2003-03-14 | Azetidine derivatives as ccr-3 receptor antagonists |
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| WO2004089296A2 (en) | 2003-04-03 | 2004-10-21 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
| EP1638939A2 (en) * | 2003-06-24 | 2006-03-29 | Neurosearch A/S | Aza-ring derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
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| US20090018092A1 (en) | 2004-03-16 | 2009-01-15 | The Regents Of The University Of California | Reducing Nephropathy with Inhibitors of Soluble Epoxide Hydrolase and Epoxyeicosanoids |
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| AU2005295167B2 (en) | 2004-10-20 | 2012-05-10 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
| GB0607196D0 (en) * | 2006-04-11 | 2006-05-17 | Prosidion Ltd | G-protein coupled receptor agonists |
| GB0720390D0 (en) * | 2007-10-18 | 2007-11-28 | Prosidion Ltd | G-Protein coupled receptor agonists |
| GB0720389D0 (en) * | 2007-10-18 | 2008-11-12 | Prosidion Ltd | G-Protein Coupled Receptor Agonists |
| WO2010129351A1 (en) | 2009-04-28 | 2010-11-11 | Schepens Eye Research Institute | Method to identify and treat age-related macular degeneration |
| HRP20191842T1 (hr) | 2011-01-07 | 2019-12-27 | Novartis Ag | Formulacije imunosupresiva |
| EP3613435A1 (en) | 2015-01-28 | 2020-02-26 | Universite De Bordeaux | Chemokine receptor cxcr4 inhibitors for treating and/or preventing chronic obstructive pulmonary disease |
| SG11202007072RA (en) | 2018-01-26 | 2020-08-28 | Rapt Therapeutics Inc | Chemokine receptor modulators and uses thereof |
| CN110498750B (zh) * | 2019-09-02 | 2021-10-15 | 南通大学 | 一种(r)-4-羟基-1-甲氧基丁-2-基氨基甲酸叔丁酯的合成方法 |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法 |
| US12221463B2 (en) | 2020-08-07 | 2025-02-11 | The Board Of Regents Of The University Of Oklahoma | Method of promoting wound healing by inhibiting CCR3 |
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| GB2093456B (en) | 1980-10-08 | 1984-12-05 | Robins Co Inc A H | 1-r1-3-phenozyazetidines |
| US5095014A (en) * | 1990-12-07 | 1992-03-10 | A. H. Robins Company, Incorporated | 3-(2-chloro-4-(trifluoromethyl)phenoxy)-1-azetidine carboxamides having anticonvulsant activity |
| DE4335718A1 (de) * | 1993-10-20 | 1995-04-27 | Merck Patent Gmbh | Cyclische Aminderivate |
| AU8576098A (en) * | 1997-07-25 | 1999-02-16 | Merck & Co., Inc. | Cyclic amine modulators of chemokine receptor activity |
| IL125658A0 (en) * | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
| PE20001420A1 (es) * | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
| GB0019006D0 (en) * | 2000-08-04 | 2000-09-20 | Astrazeneca Ab | Novel compounds |
| GB0117387D0 (en) * | 2001-07-17 | 2001-09-05 | Novartis Ag | Organic compounds |
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| JP2009102325A (ja) | 2009-05-14 |
| NZ535082A (en) | 2006-08-31 |
| JP2005526773A (ja) | 2005-09-08 |
| TW200800167A (en) | 2008-01-01 |
| BR0308419A (pt) | 2005-01-18 |
| CA2479266A1 (en) | 2003-09-25 |
| KR100706270B1 (ko) | 2007-04-11 |
| PL371055A1 (en) | 2005-06-13 |
| NO20044373L (no) | 2004-10-14 |
| AU2003227072A1 (en) | 2003-09-29 |
| AR041786A1 (es) | 2005-06-01 |
| MXPA04009057A (es) | 2005-01-25 |
| CN1638761A (zh) | 2005-07-13 |
| RU2004130487A (ru) | 2005-07-10 |
| US7288537B2 (en) | 2007-10-30 |
| IL164016A0 (en) | 2005-12-18 |
| CO5611125A2 (es) | 2006-02-28 |
| US20050222118A1 (en) | 2005-10-06 |
| WO2003077907A1 (en) | 2003-09-25 |
| KR20040091690A (ko) | 2004-10-28 |
| EP1487435A1 (en) | 2004-12-22 |
| AU2003227072B2 (en) | 2006-08-10 |
| RU2314292C2 (ru) | 2008-01-10 |
| TW200305395A (en) | 2003-11-01 |
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