TWI422369B - κ選擇性類鴉片受體拮抗劑 - Google Patents
κ選擇性類鴉片受體拮抗劑 Download PDFInfo
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- TWI422369B TWI422369B TW098101083A TW98101083A TWI422369B TW I422369 B TWI422369 B TW I422369B TW 098101083 A TW098101083 A TW 098101083A TW 98101083 A TW98101083 A TW 98101083A TW I422369 B TWI422369 B TW I422369B
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- pharmaceutically acceptable
- acceptable salt
- ethanol
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| CA2858752C (en) | 2011-12-09 | 2019-12-31 | Research Triangle Institute | 1-substituted 4-arylpiperazines as kappa opioid receptor antagonists |
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| US8551986B2 (en) * | 2005-12-08 | 2013-10-08 | The Mclean Hospital Corporation | Treatment of sequelae of psychiatric disorders |
| CA2646899C (en) | 2006-04-04 | 2014-05-06 | Holger Lars Hermann | Use of compositions containing kappa-opioid receptor antagonists for the treatment of dissociative disorders |
| JP5362565B2 (ja) | 2006-08-09 | 2013-12-11 | スミスクライン ビーチャム コーポレーション | オピオイド受容体のアンタゴニストまたはインバースアゴニストである新規化合物 |
| US20100222345A1 (en) | 2006-08-09 | 2010-09-02 | Caroline Jean Diaz | Novel compounds as antagonists or inverse agonists for opioid receptors |
| KR20090051778A (ko) | 2006-09-08 | 2009-05-22 | 화이자 프로덕츠 인코포레이티드 | 다이아릴 에터 유도체 및 이의 용도 |
| TWI422369B (zh) * | 2008-01-22 | 2014-01-11 | Lilly Co Eli | κ選擇性類鴉片受體拮抗劑 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004026305A1 (en) * | 2002-09-19 | 2004-04-01 | Eli Lilly And Company | Diaryl ethers as opioid receptor antagonist |
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