JP7448961B2 - チエノピリジン化合物の混合ジスルフィド結合体及びそれらの使用 - Google Patents
チエノピリジン化合物の混合ジスルフィド結合体及びそれらの使用 Download PDFInfo
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- JP7448961B2 JP7448961B2 JP2021087169A JP2021087169A JP7448961B2 JP 7448961 B2 JP7448961 B2 JP 7448961B2 JP 2021087169 A JP2021087169 A JP 2021087169A JP 2021087169 A JP2021087169 A JP 2021087169A JP 7448961 B2 JP7448961 B2 JP 7448961B2
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- thienopyridine
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- mixed disulfide
- pharmaceutical composition
- compound
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Classifications
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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Description
本出願は、2015年4月30日に出願された米国仮特許出願第62/155,231号に対する優先権を主張し、本明細書に参照として含まれる。
これらの薬学的に許容される塩、溶媒和物、及び/又はプロドラッグを含み、ここで、R4は、脂肪族及び/又は芳香族置換基を有するエステル部分、脂肪族及び/又は芳香族置換基を有するケトン部分、及び脂肪族及び/又は芳香族置換基を有するアミド部分からなる群から選択される。
)内の特定の立体化学的配置に制限されない。いくつかの実施形態では、R4置換基に接続された二重結合は、Z又はシス配置のいずれかである。例えば、いくつかの実施形態では、化学式(I)は、次の立体化学的配置のいずれかによって表される。
を形成する。例えば、いくつかの実施形態では、R4置換基は、正の電荷を有する窒素部分
を有し、これは、ハロゲン(例えば、Cl-、Br-、Fl-、など)と結合してアンモニウム塩
を生成する。
からなる群から選択される。
からなる群から選択される。
から選択される。
本明細書で使用される「チエノピリジン化合物」という用語は、抗血小板活性に使用されるADP受容体/P2Y12阻害剤の種類を意味する。例えば、クロピドグレル(Plavix)、チクロピジン(Ticlid)、及びプラスグレル(Effient)を含んでいるが、これらに限定されることはない。
Chapter 5: "Design and Applications of Prodrugs"; Design of Prodrugs, H. Bundgaard(ed.), Elsevier, 1985; Prodrugs:Topical and Ocular Drug Delivery, K. B. Sloan (ed.), Marcel Dekker, 1998; Methods in Enzymology, K. Widder, et al. (eds.), Vol
. 42, Academic Press, 1985, particularly pp. 309-396;Burger's Medicinal Chemistry and Drug Discovery, 5th Ed., M. Wolff(ed.), John Wiley & Sons, 1995, particularlyVol. 1 and pp. 172-178 and pp. 949-982; Pro-Drugs as Novel Delivery Systems, T. Higuchi andV. Stella(eds.), Am. Chem. Soc., 1975; and Bioreversible Carriers in Drug Design, E. B. Roche(ed.), Elsevier, 1987に記載されている。
スキーム3内で、SRの例は、
を含むが、これらに制限されない。
)内の特定の立体化学的配置に制限されない。いくつかの実施形態では、R4置換基に接続された二重結合は、Z又はシス配置のいずれかである。例えば、いくつかの実施形態では、化学式(I)は、次の立体化学的配置のいずれかによって表される。
を形成する。
からなる群から選択される。
からなる群から選択される。
から選択される。
本明細書で言及された各特許文書及び科学論文の全体の開示は、全ての目的のために参照として援用される。
本発明は、その思想又は本質的な特徴から逸脱することなく、他の特定の形態で実現することができる。従って、上記の実施形態は、本明細書に記載された本発明限定するのではなく、全ての点で例示的であるとみなされるべきである。従って、本発明の範囲は、上記の説明ではなく添付の特許請求の範囲によって示され、特許請求の範囲の等価物の意味及び範囲内に入る全ての変更は、本明細書に含まれることが意図される。
Claims (4)
- 患者の心血管疾患を治療、改善又は予防する方法に使用するための薬学的組成物であって、
前記治療、改善又は予防は、前記薬学的組成物の治療的有効量を前記患者に投与する工程を含み、
前記心血管疾患は、冠動脈疾患、末梢血管疾患、アテローム血栓症、及び脳血管疾患からなる群から選択され、
前記薬学的組成物は、チエノピリジン化合物の混合ジスルフィド結合体を含む薬学的組成物であって、
前記薬学的組成物は、静脈内投与のために構成され、
前記チエノピリジン化合物の混合ジスルフィド結合体は化学式(I)内に含まれる化合物であって、又はこれらの薬学的に許容される塩の形態であり、
ここで、R1は-CO-OCH3、
からなる群から選択され、
ここで、R2は、
からなる群から選択され、
ここで、R3はCl、Br、I、F、CN、NO2、CF3、H、OCH3からなる群から選択され、
ここで、R4は-COOCH3、-COOCH2CH3、COOCF3、
からなる群から選択される、薬学的組成物。 - 疾患の治療に使用するための請求項1に記載の薬学的組成物であって、
前記治療は、経皮的冠動脈インターベンション処置中に患者の静脈内に投与することを含む、薬学的組成物。 - 前記経皮的冠動脈インターベンション処置は、冠動脈形成術である、請求項2に記載の使用するための薬学的組成物。
- 化学式(I)の立体化学的配置は、
からなる群から選択される、請求項1に記載の使用するための薬学的組成物。
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SG11201708738YA (en) * | 2015-04-30 | 2017-11-29 | Univ Michigan Regents | Mixed disulfide conjugates of thienopyridine compounds and uses thereof |
SG11202007273WA (en) * | 2018-01-31 | 2020-08-28 | Univ Michigan Regents | Biocatalyst and methods for synthesizing mixed disulfide conjugates of thienopyridine compounds |
US11642335B2 (en) * | 2019-09-26 | 2023-05-09 | Board Of Regents, The University Of Texas System | Chemical synthesis of clopidogrel active metabolites and disulfide conjugate prodrugs |
CN111484446A (zh) * | 2020-04-02 | 2020-08-04 | 北京翼方生物科技有限责任公司 | 氯吡格雷代谢活性体二硫衍生物、其制备方法及医药用途 |
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WO2014109987A1 (en) | 2013-01-09 | 2014-07-17 | The Regents Of The University Of Michigan | Mixed disulfide conjugates of thienopyridine compounds and uses thereof |
JP6893030B2 (ja) | 2015-04-30 | 2021-06-23 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | チエノピリジン化合物の混合ジスルフィド結合体及びそれらの使用 |
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US3989816A (en) | 1975-06-19 | 1976-11-02 | Nelson Research & Development Company | Vehicle composition containing 1-substituted azacycloheptan-2-ones |
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JPH03193969A (ja) * | 1989-12-20 | 1991-08-23 | Idemitsu Kosan Co Ltd | 炭素繊維の電解処理方法 |
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CA2983313C (en) | 2020-08-25 |
WO2016176644A1 (en) | 2016-11-03 |
KR20220162885A (ko) | 2022-12-08 |
EP3288590A1 (en) | 2018-03-07 |
JP2021121626A (ja) | 2021-08-26 |
HK1251855A1 (zh) | 2019-04-18 |
MX371538B (es) | 2020-01-30 |
EP3288590B1 (en) | 2021-03-03 |
CA2983313A1 (en) | 2016-11-03 |
JP2024059795A (ja) | 2024-05-01 |
JP2018514532A (ja) | 2018-06-07 |
KR20170141758A (ko) | 2017-12-26 |
DK3288590T3 (da) | 2021-04-06 |
CN116478086A (zh) | 2023-07-25 |
US20180155289A1 (en) | 2018-06-07 |
EA201792085A1 (ru) | 2018-05-31 |
KR20200043521A (ko) | 2020-04-27 |
EP3288590A4 (en) | 2018-10-31 |
MX2017013772A (es) | 2018-02-21 |
SG11201708738YA (en) | 2017-11-29 |
US10173980B2 (en) | 2019-01-08 |
CN107921135A (zh) | 2018-04-17 |
JP6893030B2 (ja) | 2021-06-23 |
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