JP2022504403A - 心血管疾患の処置に有用な新規化合物 - Google Patents
心血管疾患の処置に有用な新規化合物 Download PDFInfo
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- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- LDRXLIZMSQWXDL-UHFFFAOYSA-N C(C1)C11C2OCCC2OC1 Chemical compound C(C1)C11C2OCCC2OC1 LDRXLIZMSQWXDL-UHFFFAOYSA-N 0.000 description 1
- UYSGDSIEZTXDIF-IDKOKCKLSA-N C[C@@H](COC1CCCCC2)C1[O]2=N Chemical compound C[C@@H](COC1CCCCC2)C1[O]2=N UYSGDSIEZTXDIF-IDKOKCKLSA-N 0.000 description 1
- NMBIAKNJPUTPKX-UHFFFAOYSA-N N=[O](CCC12)C1C1(CC1)C[O]2=N Chemical compound N=[O](CCC12)C1C1(CC1)C[O]2=N NMBIAKNJPUTPKX-UHFFFAOYSA-N 0.000 description 1
- UCISVRUWWXPEFS-UHFFFAOYSA-N NC(NCC(/[O]=C\C1C2OCC3(CC3)C2OC1)=O)=O Chemical compound NC(NCC(/[O]=C\C1C2OCC3(CC3)C2OC1)=O)=O UCISVRUWWXPEFS-UHFFFAOYSA-N 0.000 description 1
- XCDCZKDQIPQWMP-UHFFFAOYSA-N NCC(/[O]=C\C(COC1C2(CC2)C2)C1[O]2=N)=O Chemical compound NCC(/[O]=C\C(COC1C2(CC2)C2)C1[O]2=N)=O XCDCZKDQIPQWMP-UHFFFAOYSA-N 0.000 description 1
- NIXKBAZVOQAHGC-UHFFFAOYSA-N phenylmethanesulfonic acid Chemical class OS(=O)(=O)CC1=CC=CC=C1 NIXKBAZVOQAHGC-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
本出願は、2019年10月12日に出願された米国非仮特許出願第16/600,476号の利益を主張し、当該出願は、参照によりその全体が本明細書に組み込まれる。
R1は、存在せず、
あるいは、R1は、(イソソルビド部分に結合しているR1の右側部分):(CH2)2O、(CH2)2NH、(CH2)3O、(CH2)3NH、CH2C(=O)O、およびCH2C(=O)NHから選択され、
R2は、(イソソルビド部分に結合しているR2の右側部分):(CH2)2O、(CH2)2NH、(CH2)3O、(CH2)3NH、CH2C(=O)O、CH2C(=O)NH、CH2OC(=O)O、CH2OC(=O)NH、CH2NHC(=O)O、およびCH2NHC(=O)NHから選択される、化合物、
またはその薬学的に許容される塩を提供する。
本出願に提示される定義で提供される例は、特に明記されていない限り、非包括的である。それらには、記載された例が含まれるが、これらに限定されない。
本発明では、本発明の化合物は、任意の好都合な方法で(例えば、経腸的または非経口的に)投与することができる。投与方法の例には、経口および経皮が含まれる。当業者は、本発明の化合物の投与経路が大きく変動し得ることを認識している。他の経口投与に加えて、持続放出組成物が好まれ得る。他の許容される経路には、注射(例えば、静脈内、筋肉内、皮下、および腹腔内)、皮下インプラント、ならびに口腔、舌下、局所、直腸、膣、および鼻腔内投与が含まれ得る。経口製剤の例には、錠剤、コーティング錠剤、軟質および硬質ゼラチンカプセル剤、溶剤、乳剤、ならびに懸濁剤が含まれる。本発明の化合物を血管壁に直接送達し得るカテーテルによって配置されたステントなどの薬剤溶出構造を含む、生体侵食性(bioerodible)、非生体侵食性、生分解性、および非生分解性投与システムも使用し得る。
成分 mg/錠
活性成分 100
粉末乳糖 95
ホワイトコーンスターチ 35
ポリビニルピロリドン 8
Naカルボキシメチルデンプン 10
ステアリン酸マグネシウム 2
錠剤重量 250
成分 mg/カプセル
活性成分 50
結晶ラクトース 60
微結晶性セルロース 39
ステアリン酸マグネシウム 1
カプセル充填重量 150
成分 mg/溶液
活性成分 1.0mg
1NHCl 20.0μl
酢酸 0.5mg
NaCl 8.0mg
フェノール 10.0mg
1N NaOH pH5まで適量
H 2O 1mLまで適量
本発明の化合物は、有機合成化学分野で既知である合成方法と一緒に、または当業者によって理解されるその変形によって、以下に記載される方法を使用して合成することができる。好ましい方法には、以下に記載されるものが含まれるが、これらに限定されない。反応は、使用される試薬および材料に適切であり、影響を受ける変換に好適な溶媒中で行われる。分子上に存在する官能基が提案された変換物と合致している必要があることが有機合成分野の当業者によって理解されるであろう。これは、所望の本発明の化合物を得るために、合成ステップの順序を変更するか、またはある特定のプロセススキームを別のものに対して選択するための判断を必要とする場合がある。この分野における任意の合成経路の計画における別の主要な考慮事項は、本発明に記載の化合物に存在する反応性官能基の保護に使用される保護基の賢明な選択であることも認識される。熟練した実施者に対して多くの選択肢を説明する信頼ある記述は、Protective Groups In Organic Synthesis.(Greene&Wuts,1991)に見出される。本明細書で引用されたすべての参考文献は、参照によりその全体が本明細書に組み込まれる。
本化合物については2つの主な適応症がある。第1の適応症は狭心症治療剤としてである。化合物は、冠状血管拡張剤として作用する薬剤とともに、冠状動脈疾患の状況における運動能力を改善することが期待される。第2の適応症は、心血管疾患の二次予防であり、この用途では、血管拡張は虚血性プレコンディショニングと同様に考えられる。
Alleman,R.J.,Tsang,A.M.,Ryan,T.E.,Patteson,D.J.,McClung,J.M.,Spangenburg,E.E.et al.(2016).Exercise-induced protection against reperfusion arrhythmia involves stabilization of mitochondrial energetics.American Journal of Physiology-Heart and Circulatory Physiology,310,H1360-H1370.
本出願は、2019年10月12日に出願された米国非仮特許出願第16/600,476号の利益を主張し、当該出願は、参照によりその全体が本明細書に組み込まれる。
R1は、存在せず、
あるいは、R1は、(イソソルビド部分に結合しているR1の右側部分):(CH2)2O、(CH2)2NH、(CH2)3O、(CH2)3NH、CH2C(=O)O、およびCH2C(=O)NHから選択され、
R2は、(イソソルビド部分に結合しているR2の右側部分):(CH2)2O、(CH2)2NH、(CH2)3O、(CH2)3NH、CH2C(=O)O、CH2C(=O)NH、CH2OC(=O)O、CH2OC(=O)NH、CH2NHC(=O)O、およびCH2NHC(=O)NHから選択される、化合物、
またはその薬学的に許容される塩を提供する。
本出願に提示される定義で提供される例は、特に明記されていない限り、非包括的である。それらには、記載された例が含まれるが、これらに限定されない。
本発明では、本発明の化合物は、任意の好都合な方法で(例えば、経腸的または非経口的に)投与することができる。投与方法の例には、経口および経皮が含まれる。当業者は、本発明の化合物の投与経路が大きく変動し得ることを認識している。他の経口投与に加えて、持続放出組成物が好まれ得る。他の許容される経路には、注射(例えば、静脈内、筋肉内、皮下、および腹腔内)、皮下インプラント、ならびに口腔、舌下、局所、直腸、膣、および鼻腔内投与が含まれ得る。経口製剤の例には、錠剤、コーティング錠剤、軟質および硬質ゼラチンカプセル剤、溶剤、乳剤、ならびに懸濁剤が含まれる。本発明の化合物を血管壁に直接送達し得るカテーテルによって配置されたステントなどの薬剤溶出構造を含む、生体侵食性(bioerodible)、非生体侵食性、生分解性、および非生分解性投与システムも使用し得る。
成分 mg/錠
活性成分 100
粉末乳糖 95
ホワイトコーンスターチ 35
ポリビニルピロリドン 8
Naカルボキシメチルデンプン 10
ステアリン酸マグネシウム 2
錠剤重量 250
成分 mg/カプセル
活性成分 50
結晶ラクトース 60
微結晶性セルロース 39
ステアリン酸マグネシウム 1
カプセル充填重量 150
成分 mg/溶液
活性成分 1.0mg
1NHCl 20.0μl
酢酸 0.5mg
NaCl 8.0mg
フェノール 10.0mg
1N NaOH pH5まで適量
H 2O 1mLまで適量
本発明の化合物は、有機合成化学分野で既知である合成方法と一緒に、または当業者によって理解されるその変形によって、以下に記載される方法を使用して合成することができる。好ましい方法には、以下に記載されるものが含まれるが、これらに限定されない。反応は、使用される試薬および材料に適切であり、影響を受ける変換に好適な溶媒中で行われる。分子上に存在する官能基が提案された変換物と合致している必要があることが有機合成分野の当業者によって理解されるであろう。これは、所望の本発明の化合物を得るために、合成ステップの順序を変更するか、またはある特定のプロセススキームを別のものに対して選択するための判断を必要とする場合がある。この分野における任意の合成経路の計画における別の主要な考慮事項は、本発明に記載の化合物に存在する反応性官能基の保護に使用される保護基の賢明な選択であることも認識される。熟練した実施者に対して多くの選択肢を説明する信頼ある記述は、Protective Groups In Organic Synthesis.(Greene&Wuts,1991)に見出される。本明細書で引用されたすべての参考文献は、参照によりその全体が本明細書に組み込まれる。
本化合物については2つの主な適応症がある。第1の適応症は狭心症治療剤としてである。化合物は、冠状血管拡張剤として作用する薬剤とともに、冠状動脈疾患の状況における運動能力を改善することが期待される。第2の適応症は、心血管疾患の二次予防であり、この用途では、血管拡張は虚血性プレコンディショニングと同様に考えられる。
Alleman,R.J.,Tsang,A.M.,Ryan,T.E.,Patteson,D.J.,McClung,J.M.,Spangenburg,E.E.et al.(2016).Exercise-induced protection against reperfusion arrhythmia involves stabilization of mitochondrial energetics.American Journal of Physiology-Heart and Circulatory Physiology,310,H1360-H1370.
Claims (20)
- R1が、存在しない、請求項2に記載の化合物、
またはその薬学的に許容される塩。 - R1が、(CH2)2O、(CH2)2NH、(CH2)3O、および(CH2)3NHから選択される、請求項2に記載の化合物、
またはその薬学的に許容される塩。 - R1が、(CH2)2Oである、請求項2に記載の化合物、またはその薬学的に許容される塩。
- R1が、(CH2)2NHである、請求項2に記載の化合物、またはその薬学的に許容される塩。
- R1が、CH2C(=O)Oである、請求項2に記載の化合物、またはその薬学的に許容される塩。
- R1が、CH2C(=O)NHである、請求項2に記載の化合物、またはその薬学的に許容される塩。
- R2が、(CH2)2O、(CH2)2NH、(CH2)3O、(CH2)3NH、CH2OC(=O)O、CH2OC(=O)NH、CH2NHC(=O)O、およびCH2NHC(=O)NHから選択される、請求項9に記載の化合物、
またはその薬学的に許容される塩。 - R2が、CH2C(=O)Oである、請求項9に記載の化合物、またはその薬学的に許容される塩。
- R2が、CH2C(=O)NHである、請求項9に記載の化合物、またはその薬学的に許容される塩。
- R1が、存在しない、請求項13に記載の化合物、
またはその薬学的に許容される塩。 - R1が、(CH2)2O、(CH2)2NH、(CH2)3O、および(CH2)3NHから選択される、請求項13に記載の化合物、
またはその薬学的に許容される塩。 - R1が、CH2 C(=O)Oである、請求項13に記載の化合物、またはその薬学的に許容される塩。
- R1が、CH2C(=O)NHである、請求項13に記載の化合物、またはその薬学的に許容される塩。
- 治療有効量の請求項1に記載の化合物および薬学的に許容される担体を含む、医薬組成物。
- 疾患を処置する方法であって、それを必要とする哺乳動物に、治療有効量の請求項1に記載の化合物を投与することを含み、前記疾患が心血管疾患である、方法。
- 前記心血管疾患が、冠状動脈疾患、心筋梗塞、心不全、心不整脈、電気生理学的心臓障害、先天性心血管異常、発達性心血管異常、炎症性心筋症、川崎病、感染性心筋症、突然死/心臓停止、アテローム性動脈硬化症、アテローム性動脈硬化性心血管疾患、心臓弁疾患、静脈不全、心臓血栓症、血管血栓症、血栓塞栓症、末梢動脈疾患、大動脈瘤、大動脈解離、血管動脈瘤、血管解離、脳卒中、全身性高血圧症、および肺高血圧症から選択される、請求項19に記載の疾患を処置する方法。
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Publication number | Publication date |
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EP3873457A4 (en) | 2022-08-24 |
CN113226301A (zh) | 2021-08-06 |
CA3115113A1 (en) | 2020-05-07 |
US20200181161A1 (en) | 2020-06-11 |
IL282703A (en) | 2021-06-30 |
EP3873457B1 (en) | 2024-02-07 |
EP3873457C0 (en) | 2024-02-07 |
IL282703B1 (en) | 2024-01-01 |
IL282703B2 (en) | 2024-05-01 |
WO2020092180A1 (en) | 2020-05-07 |
EP3873457A1 (en) | 2021-09-08 |
JP7452881B2 (ja) | 2024-03-19 |
US10913748B2 (en) | 2021-02-09 |
AU2019373199A1 (en) | 2021-03-11 |
MX2021003888A (es) | 2021-06-04 |
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