JP2023063281A - 治療のためのベンズアミド共結晶 - Google Patents
治療のためのベンズアミド共結晶 Download PDFInfo
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- JP2023063281A JP2023063281A JP2022176753A JP2022176753A JP2023063281A JP 2023063281 A JP2023063281 A JP 2023063281A JP 2022176753 A JP2022176753 A JP 2022176753A JP 2022176753 A JP2022176753 A JP 2022176753A JP 2023063281 A JP2023063281 A JP 2023063281A
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- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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Abstract
Description
本出願は、2021年9月2日に出願された米国仮出願第63/239,979号を基礎とする優先権を主張するものであり、同出願の開示は、参照を介して本明細書に組み入れられる。
3-{[5-(アゼチジン-1-イルカルボニル)ピラジン-2-イル]オキシ}-5-{[(1S)-1-メチル-2-(メチルオキシ)エチル]オキシ}-N-(5-メチルピラジン-2-イル)ベンズアミド
Table 1
Table 2
Table 3
る。室温での共結晶2の単結晶データ及び構造に基づいて計算されたXRPDパターンを図9に示す。実験パターンに存在する好ましい配向効果により、僅かな強度差が図7と図9との間に生じていることが分かる。
Table 4
Table 5
Table 6
Table 7
Table 8
Table 9
Table 10
50mgの共結晶5A、5B、5C、及び5Dを、2mLのニトロメタン、アセトニトリル又は1:1(v/v)酢酸エチル/メチルtert-ブチルエーテルで24時間室温で別々にスラリー化した。共結晶5A、5B、5C、及び5Dのそれぞれ10mgを合わせ、2mLのニトロメタン、アセトニトリル又は1:1(v/v)酢酸エチル/メチルtert-ブチルエーテルで24時間スラリー化する実験の第2のセットを行った。この時間の後、得られた生成物をすべて真空下で濾過し、XRPDによって分析した。XRPDにより、共結晶5の異なる形態のすべてが、単独で又は形態の組み合わせとしてスラリー化された場合に試験された3つの溶媒すべてにおいて、単一の多形体、形態5Aに変換されたことが確認された。これにより、共結晶5の異なる形態のすべてを単一の多形体に変換することが可能であること、及び共結晶5Aが、熱力学的に最も安定な1:1 ベンズアミドゲンチジン酸共結晶の形態であることが確認される。
Table 11
Table 12
Claims (23)
- 以下からなる群から選択される、ベンズアミド共結晶
1:1 ベンズアミドフマル酸共結晶、1:1 ベンズアミドマレイン酸共結晶、1:1 ベンズアミドマロン酸共結晶、1:1 ベンズアミドL-酒石酸水和物共結晶、及び1:1 ベンズアミドゲンチジン酸共結晶。 - 1:1 ベンズアミドゲンチジン酸共結晶が、1:1 ベンズアミドゲンチジン酸形態1共結晶、1:1 ベンズアミドゲンチジン酸形態2共結晶、1:1 ベンズアミドゲンチジン酸形態3共結晶、及び1:1 ベンズアミドゲンチジン酸形態4共結晶からなる群から選択される、請求項1に記載のベンズアミド共結晶。
- 1:1 ベンズアミドフマル酸共結晶が、以下の少なくとも1つを特徴とする、請求項1に記載のベンズアミド共結晶:
292(4)Kの温度における三斜晶P1結晶系空間群;
単位格子寸法a=9.8435(3)Å、b=11.4054(3)Å、c=15.0743(6)Å、α=95.605(3)°、β=108.628(3)°、及びγ=113.219(3)°;
6.4、8.7、14.4、15.9、22.2及び27.3°2θ±0.2°2θから選択される少なくとも3つのピークを有するX線粉末回折パターン;又は
図1と実質的に同じであるX線粉末回折パターン。 - 1:1 ベンズアミドマレイン酸共結晶が、以下の少なくとも1つを特徴とする、請求項1に記載のベンズアミド共結晶:
292(2)Kの温度における三斜晶P1結晶系空間群;
単位格子寸法a=7.8811(2)Å、b=9.6568(2)Å、c=19.2761(4)Å、α=97.4767(17)°、β=97.5064(18)°、及びγ=96.242(2)°;
4.7、9.3、12.2、12.8、14.5及び15.6°2θ±0.2°2θから選択される少なくとも3つのピークを有するX線粉末回折パターン;又は
図7と実質的に同じであるX線粉末回折パターン。 - 1:1 ベンズアミドマロン酸共結晶が、以下の少なくとも1つを特徴とする、請求項1に記載のベンズアミド共結晶:
6.3、8.7、9.7、11.1、12.6及び13.4°2θ±0.2°2θから選択される少なくとも3つのピークを有するX線粉末回折パターン;又は
図13と実質的に同じであるX線粉末回折パターン。 - 1:1 ベンズアミドL-酒石酸水和物共結晶が、以下の少なくとも1つを特徴とする、請求項1に記載のベンズアミド共結晶:
3.5、5.4、14.8、16.5、18.6及び19.3°2θ±0.2°2θから選択される少なくとも3つのピークを有するX線粉末回折パターン;又は
図16と実質的に同じであるX線粉末回折パターン。 - 1:1 ベンズアミドゲンチジン酸形態1共結晶が、
以下の少なくとも1つを特徴とする、請求項1に記載のベンズアミド共結晶:
9.1、9.9、12.2、12.8、18.4及び19.7°2θ±0.2°2θから選択される少なくとも3つのピークを有するX線粉末回折パターン;又は
図20と実質的に同じであるX線粉末回折パターン
のうちの少なくとも1つを特徴とする、請求項2に記載のベンズアミド共結晶。 - 1:1 ベンズアミドゲンチジン酸形態2共結晶が、
図24と実質的に同じであるX線粉末回折パターン
を特徴とする、請求項2に記載のベンズアミド共結晶。 - 1:1 ベンズアミドゲンチジン酸形態3共結晶が、
図27と実質的に同じであるX線粉末回折パターン
を特徴とする、請求項2に記載のベンズアミド共結晶。 - 1:1 ベンズアミドゲンチジン酸形態4共結晶が、
図30と実質的に同じであるX線粉末回折パターン
を特徴とする、請求項2に記載のベンズアミド共結晶。 - 治療有効量の請求項1~10のいずれかに記載のベンズアミド共結晶及び薬学的に許容される担体を含む医薬組成物。
- 医薬組成物が、固体投与形態又は溶液である、請求項11に記載の医薬組成物。
- ベンズアミド共結晶の治療有効量が、約100mg~約1000mgである、請求項11に記載の医薬組成物。
- 医薬組成物が局所製剤である、請求項11~13のいずれかに記載の医薬組成物。
- 吸入可能な製剤である、請求項11~13のいずれかに記載の医薬組成物。
- 医薬組成物が注射可能な製剤である、請求項11~13のいずれかに記載の医薬組成物。
- 以下の工程を含む、液体医薬組成物を調製する方法:
請求項1~10のいずれかに記載のベンズアミド共結晶を薬学的に許容される溶媒に溶解すること。 - 以下の工程を含む、グルコキナーゼを介して媒介される、疾患、障害又は状態を処置又は予防する方法:
治療有効量の請求項1~10のいずれかに記載のベンズアミド共結晶を、それを必要とする対象に投与すること。 - 以下の工程を含む、グルコキナーゼを介して媒介される、疾患、障害又は状態を処置又は予防する方法:
治療有効量の請求項11~16のいずれかに記載の医薬組成物を、それを必要とする対象に投与すること。 - 以下の工程を含む、T細胞媒介性の、自己免疫疾患、障害、又は状態を処置又は予防する方法:
治療有効量の請求項1~10のいずれかに記載のベンズアミド共結晶を、それを必要とする対象に投与すること。 - 以下の工程を含む、T細胞媒介性の、自己免疫疾患、障害、又は状態を処置又は予防する方法:
治療有効量の請求項11~16のいずれかに記載の医薬組成物を、それを必要とする対象に投与すること。 - T細胞媒介性の、自己免疫疾患、障害、又は状態が、以下から選択される、請求項20に記載の方法:
ブドウ膜炎、橋本甲状腺炎、乾癬、動脈硬化症、自己免疫性アジソン病、自己免疫性肝炎、自己免疫性心筋炎、自己免疫性膵炎、自己免疫性網膜症、セリアック病、クローン病、円板状ループス、特発性肺線維症、過敏性腸症候群、ループス腎炎、自己免疫性メニエール病、多発性硬化症、乾癬性関節炎、関節リウマチ、サルコイドーシス、全身性ループス、潰瘍性大腸炎、及び甲状腺炎。 - T細胞媒介性の、自己免疫疾患、障害、又は状態が、以下から選択される、請求項21に記載の方法:
ブドウ膜炎、橋本甲状腺炎、乾癬、動脈硬化症、自己免疫性アジソン病、自己免疫性肝炎、自己免疫性心筋炎、自己免疫性膵炎、自己免疫性網膜症、セリアック病、クローン病、円板状ループス、特発性肺線維症、過敏性腸症候群、ループス腎炎、自己免疫性メニエール病、多発性硬化症、乾癬性関節炎、関節リウマチ、サルコイドーシス、全身性ループス、潰瘍性大腸炎、及び甲状腺炎。
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