JP5726301B2 - 新規抗ヒスタミン剤 - Google Patents
新規抗ヒスタミン剤 Download PDFInfo
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- JP5726301B2 JP5726301B2 JP2013517304A JP2013517304A JP5726301B2 JP 5726301 B2 JP5726301 B2 JP 5726301B2 JP 2013517304 A JP2013517304 A JP 2013517304A JP 2013517304 A JP2013517304 A JP 2013517304A JP 5726301 B2 JP5726301 B2 JP 5726301B2
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- pharmaceutically acceptable
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- 239000000739 antihistaminic agent Substances 0.000 title claims description 17
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 title claims description 13
- 230000001387 anti-histamine Effects 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 230000000172 allergic effect Effects 0.000 claims description 17
- 208000010668 atopic eczema Diseases 0.000 claims description 17
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- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 2
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 claims description 2
- IJHNSHDBIRRJRN-UHFFFAOYSA-N N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=CC=C1 IJHNSHDBIRRJRN-UHFFFAOYSA-N 0.000 claims description 2
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- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
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Description
化合物IIの調製
1H−NMR(300MHz、CD3OD):8.71(幅広シグナル、2H)、8.31(m、2H)、7.63(d、J=7.31Hz、1H)、7.18(m、4H)、5.48(dd、J=3.29Hz、J=11.70Hz、1H)、3.69(s、2H)、3.41(m、3H)、3.11(dd、J=11.7Hz、J=17.2Hz、1H)、2.8(m、4H)、2.54(s、3H)、2.45(m、2H)、2.26(m、4H)
13C−NMR(75.43MHz、CD3OD):176.35、172.20、158.73、147.00、144.65、143.31、143.26、141.15、140.03、139.69、139.47、138.65、138.62、135.85、134.06、133.72、131.91、130.33、127.01、124.08、75.81、59.36、55.47、55.42、42.30、32.75、32.03、31.81、31.77、18.38
IR(KBr):3412、1587、1474、1437、1379、1176、1086、992、874、829、663cm−1
EA:予測(C30H30CIN3O4・NH3・H2O):C63.54;H6.22;N9.88
観測:C63.47;H6.41;N9.61
化合物IIのヒスタミンH1受容体阻害能の測定
化合物IIの抗H1活性を、標準的なH1結合アッセイを用いて測定した。試験はSmit et al. (Brit. J. Pharmacol. 1996 117(6), 1071−1080)に基づく手順に従って行った;結合はヒトH1受容体を発現する組換HEK−293細胞上で行った。対照化合物は1nMの[3H]−ピリラミンだった。組換HEK−293誘導膜を異なる濃度の化合物IIの存在下で[3H]−ピリラミンと22℃で60分間培養した。測定はシンチレーションカウンティングを用いて行った。
化合物IIの液体製剤
Claims (20)
- 式II:
の化合物またはその薬学的に許容される塩。 - 治療に用いられる請求項1に記載の化合物。
- アレルギー性障害の治療に用いられる請求項1に記載の化合物。
- アレルギー性鼻炎または蕁麻疹の治療に用いられる請求項1に記載の化合物。
- 請求項1に記載の化合物および1つ以上の薬学的に許容される賦形剤を含む医薬組成物。
- 水性液体医薬組成物である、請求項5に記載の医薬組成物。
- 0.01g/L〜10g/Lの請求項1に記載の化合物を含む、請求項6に記載の医薬組成物。
- 経口使用を意図する、請求項5〜7のいずれかに記載の医薬組成物。
- 第2抗ヒスタミン剤を含む、請求項5〜8のいずれかに記載の医薬組成物。
- 前記第2抗ヒスタミン剤がロラタジン、デスロラタジン、ルパタジン、クレマスチン、ジフェンヒドラミン、フェキソフェナジン、フェニラミン、セチリジン、エバスチン、プロメタジン、クロルフェニラミンおよびレボセチリジン、またはそれらの薬学的に許容される塩から選択される、請求項9に記載の医薬組成物。
- 前記第2抗ヒスタミン剤がルパタジンまたはその薬学的に許容される塩である、請求項10に記載の医薬組成物。
- 請求項1に記載の化合物の調製プロセスであって、式Iの化合物を式IIIの化合物と溶媒中で反応させるステップを含み、式中、LGが脱離剤である、プロセス。
- 前記溶媒がアルコール、水、アルコールおよび水の混合物ならびに水および極性非プロトン性溶媒の混合物から選択される、請求項12に記載のプロセス。
- 前記溶媒がアルコールである、請求項13に記載のプロセス。
- 請求項1に記載の化合物を有効成分として含むアレルギー性障害の治療剤。
- 前記アレルギー性障害が蕁麻疹である、請求項15に記載の治療剤。
- 前記アレルギー性障害がアレルギー性鼻炎である、請求項15に記載の治療剤。
- アレルギー性障害の治療に用いられる請求項5〜11のいずれかに記載の医薬組成物。
- 前記アレルギー性障害が蕁麻疹である、請求項18に記載の医薬組成物。
- 前記アレルギー性障害がアレルギー性鼻炎である、請求項18に記載の医薬組成物。
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US61/364,985 | 2010-07-16 | ||
PCT/EP2011/061035 WO2012001120A1 (en) | 2010-06-30 | 2011-06-30 | Rupatadine salt as an antihistaminic agent |
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TWI825013B (zh) | 2017-04-19 | 2023-12-11 | 日商帝國製藥股份有限公司 | 含有盧帕他定(rupatadine)之貼附劑 |
CN109535127B (zh) * | 2018-12-05 | 2020-10-16 | 杭州仟源保灵药业有限公司 | 富马酸卢帕他定衍生物、其制备方法及中间体和用途 |
CN110123739A (zh) * | 2019-05-14 | 2019-08-16 | 扬子江药业集团江苏紫龙药业有限公司 | 一种富马酸卢帕他定前非离子体凝胶制剂及其制备方法 |
CN110200915A (zh) * | 2019-05-14 | 2019-09-06 | 扬子江药业集团江苏紫龙药业有限公司 | 一种富马酸卢帕他定乳剂型鼻腔喷雾剂及其制备方法 |
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WO2012001120A1 (en) | 2012-01-05 |
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