JP6302846B2 - Tnap阻害剤としてのスルホンアミド化合物およびその使用 - Google Patents
Tnap阻害剤としてのスルホンアミド化合物およびその使用 Download PDFInfo
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- JP6302846B2 JP6302846B2 JP2014558836A JP2014558836A JP6302846B2 JP 6302846 B2 JP6302846 B2 JP 6302846B2 JP 2014558836 A JP2014558836 A JP 2014558836A JP 2014558836 A JP2014558836 A JP 2014558836A JP 6302846 B2 JP6302846 B2 JP 6302846B2
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or 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
- C07D277/38—Nitrogen atoms
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- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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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- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Description
本出願は、2012年2月22日に出願された米国仮特許出願第61/601,957号の利益を主張し、該文献は全体として引用されることで本明細書に組み込まれる。
本発明は、国立衛生研究所によって与えられたRC1 HL101899の下、政府の支援を受けて作られた。政府は本発明において一定の権利を有している。
Y1とY2は独立して単結合または−N(R6)−であり、ここで、Y1とY2の少なくとも1つは−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R1とR4は、水素、−F、−Cl、−Br、−I、−CN、−C(O)N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Aは、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択される。
R12とR13は、水素、ハロゲン、−CN、−OH、−C(O)−N(R17)−R18−、−C(O)−O−R19、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
ここで、
R17とR18は独立して、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R17とR18は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、および、
R19は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
R15は水素または随意に置換されたアルキルである。
Y1とY2は独立して単結合または−N(R6)−であり、ここで、Y1とY2の少なくとも1つは−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R11はCl、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R14は水素、Cl、Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Aは、水素、随意に置換されたアルキル、−OH、随意に置換されたアルコキシ、随意に置換されたハロアルコキシ、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
ここで、
AとR5が水素であり、R1がメトキシである場合、R4は水素、−Cl、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたC2−C6アルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたC2−C6アルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択される。
Y1とY2は独立して単結合または−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R11はCl、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R14は水素、Cl、Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Zは水素または−N(R17)−R18であり、
ここで、ZとR5が水素であり、R11がアルコキシである場合、R14は水素、Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたC2−C6アルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたC2−C6アルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、および、
R17とR18は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R17とR18は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成する。
Y1とY2は独立して単結合または−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R1とR4は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Wは随意に置換された5員環ヘテロアリール、ピリジン−3−イル以外の随意に置換された6員環ヘテロアリール、随意に置換された9員環ヘテロアリール、または、キノリン−3−イル以外の随意に置換された10員環ヘテロアリールからなる群から選択される。
R20は水素、ハロゲン、−CN、−OH、−C(O)−N(R17)−R18−、−C(O)−O−R19、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
ここで、
R17とR18は独立して、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R17とR18は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、および、
R19は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
R21は水素または随意に置換されたアルキルである。
本明細書で言及されるすべての出版物、特許、および、特許出願は、各々の個々の出版物、特許、または、特許出願が、具体的にかつ個別に参照されることによって組み込まれると意図されるのと同じ程度まで、参照によって本明細書に組み込まれる。
以下の記載では、様々な実施形態を完全に理解するために、特定の詳細が記載されている。しかしながら、当業者は、これらの詳細がなくとも本発明を実行し得ることができることを理解するであろう。他の例では、実施形態の記載を不必要に分かりにくくしないようにするために、周知の構造を詳細に示したり記載したりしていない。文脈が特別に必要としない限り、以下の明細書と請求項の全体にわたって、「含む(comprise)」という単語およびその変更形態(例えば、「含む(comprises)」または「含むこと(comprising)」)は、開かれた包括的な意味で、すなわち、「限定されないが、〜を含む」という意味で解釈されるものとする。さらに、本明細書で提供される見出しは、便宜上のものであり、請求される本発明の範囲や意味を解釈するものではない。
TNAPの活性を調節する化合物が本明細書に記載される。いくつかの実施形態において、本明細書に記載される化合物はTNAPを阻害する。特定の実施形態では、本明細書に記載される化合物は、過剰な鉱化に関連した疾病の処置に役立つ。
Y1とY2は独立して単結合または−N(R6)−であり、ここで、Y1とY2の少なくとも1つは−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R1とR4は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Aは、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択される。
R12とR13は、水素、ハロゲン、−CN、−OH、−C(O)−N(R17)−R18−、−C(O)−O−R19、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
ここで、
R17とR18は独立して、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R17とR18は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、および、
R19は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
R15は水素または随意に置換されたアルキルである。
いくつかの実施形態では、R7とR8は水素である。
Y1とY2は独立して単結合または−N(R6)−であり、ここで、Y1とY2の少なくとも1つは−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R11はCl、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R14は水素、Cl、Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Aは、水素、随意に置換されたアルキル、−OH、随意に置換されたアルコキシ、随意に置換されたハロアルコキシ、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
ここで、AとR5が水素であり、R1がメトキシである場合、R4は水素、−Cl、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたC2−C6アルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたC2−C6アルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択される。
[0090] 上または下に記載された特定の実施形態において、式IIの化合物が本明細書で提供され、式中、Aは−C(O)−O−R9である。
いくつかの実施形態において、R9は水素またはメチルである。
Y1とY2は独立して単結合または−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R11はCl、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R14は水素、Cl、Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Zは水素または−N(R17)−R18であり、
ここで、
ZとR5が水素であり、R11がアルコキシである場合、R14は水素、Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたC2−C6アルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたC2−C6アルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、および、
R17とR18は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R17とR18は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成する。
Y1とY2は独立して単結合または−N(R6)−であり、
L1とL2は独立して単結合または随意に置換されたアルキレンであり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R1とR4は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R2、R3、およびR5は、水素、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R6は、水素、随意に置換されたアルキル、随意に置換されたアルケニル、または、随意に置換されたアルキニルであり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Wは、随意に置換された5員環ヘテロアリール、ピリジン−3−イル以外の随意に置換された6員環ヘテロアリール、随意に置換された9員環ヘテロアリール、または、キノリン−3−イル以外の随意に置換された10員環ヘテロアリールからなる群から選択される。
R20は水素、ハロゲン、−CN、−OH、−C(O)−N(R17)−R18−、−C(O)−O−R19、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から選択され、
ここで、
R17とR18は独立して、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R17とR18は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、および、
R19は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
R21は水素または随意に置換されたアルキルである。
TNAPの活性を阻害する式I−IVの化合物と、その調剤のプロセスが本明細書に記載される。同様に、本明細書には、前記化合物の、薬学的に許容可能な塩、薬学的に許容可能な溶媒和物、薬学的に活性な代謝物、および薬学的に許容可能なプロドラッグが記載されている。少なくとも1つのこのような化合物、あるいは、そのような化合物の薬学的に許容可能な塩、薬学的に許容可能な溶媒和物、薬学的に活性な代謝物、または、薬学的に許容可能なプロドラッグ、および、薬学的に許容可能な賦形剤を含む医薬組成物も同様に提供される。
異性体
いくつかの実施形態において、本明細書に記載される化合物は、幾何異性体として存在する。他の実施形態において、本明細書に記載される化合物は、1またはそれ以上の二重結合を持つ。本発明で提示される化合物は、すべてのシス、トランス、シン、アンチ、エントゲーゲン(entgegen)(E)、および、ツザーメン(zusammen)(Z)の異性体と、それらの対応する混合物を含む。いくつかの状況において、化合物は互変異性体として存在する。本明細書に記載される化合物は、本明細書に記載される式中で可能なあらゆる互変異性体を含んでいる。いくつかの実施形態において、本明細書に記載される化合物は、1またはそれ以上のキラル中心を持っており、各々の中心は、R構造またはS構造で存在する。本明細書に記載される化合物は、ジアステレオマー、エナンチオマー、および、エピマーのすべての形状と、それたの対応する混合物を含む。本明細書で提供される化合物および方法のさらなる実施形態において、単一の調製用の段階、組み合わせ、または、相互変換に由来するエナンチオマーおよび/またはジアステレオーの混合物は、本明細書に記載される用途に有用である。いくつかの実施形態において、本明細書に記載される化合物は、一対のジアステレオマー化合物を形成するために化合物のラセミ混合物を光学的に活性な分割剤と反応させて、ジアステレオマーを分離して、光学的に純粋なエナンチオマーを回復させることによって、個々の立体異性体として調製される。いくつかの実施形態では、解離可能な複合体(dissociable complexes)が好ましい(例えば、結晶性ジアステレオマー塩)。いくつかの実施形態では、ジアステレオマーは、特徴的な物理的特性(例えば、融点、沸点、溶解度、反応性など)を備えており、これらの相違点を利用することによって分けられる。いくつかの実施形態において、ジアステレオマーは、キラルクロマトグラフィによって、または、好ましくは、溶解度の相違に基づいて分離/分割技術によって分離される。いくつかの実施形態では、光学的に純粋なエナンチオマーは、ラセミ化をもたらさない任意の実用的な手段によって、分割剤とともに回収される。
いくつかの実施形態では、本明細書に記載される化合物は、同位体で標識された形態で存在する。いくつかの実施形態では、本明細書で開示された方法は、そのような同位体で標識された化合物の投与によって疾患を処置する方法を含んでいる。いくつかの実施形態では、本明細書で開示された方法は、そのような同位体で標識された化合物を医薬組成物として投与することによって、疾患を処置する方法を含んでいる。したがって、いくつかの実施形態において、本明細書で開示される化合物は、1またはそれ以上の原子が通常自然で見られる原子質量または質量数とは異なる原子質量または質量数を備えた原子によって置き換えられるという事実を別にすれば、本明細書で列挙されるものと同一である、同位体で標識された化合物を含む。本発明の化合物に取り込み可能な同位体の例は、水素、炭素、窒素、酸素、亜リン酸、硫黄、フッ素、および、塩化物の同位体、それぞれ、2H、3H、13C、14C、15N、18O、17O、31P、32P、35S、18F、および、36Clを含む。本明細書に記載される化合物と、前述の同位体および/または他の原子の他の同位体を含有するその代謝物、薬学的に許容可能な塩、エステル、プロドラッグ、溶媒和物、水和物、または、誘導体は、本発明の範囲内である。特定の同位体で標識された化合物、例えば、3Hや14Cなどの放射性同位体が取り込まれる同位体で標識された化合物は、薬物および/または基質組織分布アッセイで有用である。トリチウム標識した、すなわち、3Hおよび炭素−14、すなわち、14Cアイソトープは、調製および検出しやすいことから特に好まれている。さらに、ジュウテリウム、すなわち、2Hのような重同位体による置換は、代謝の一層の安定に由来する特定の治療上の利点、例えば、インビボでの半減期の増加または必要投与量の減少をもたらす。いくつかの実施形態では、同位体で標識された化合物、その薬学的に許容可能な塩、エステル、プロドラッグ、溶媒和物、水和物、または、誘導体は、任意の適切な方法によって調製される。
いくつかの実施形態において、本明細書に記載される化合物は、薬学的に許容可能な塩として存在する。いくつかの実施形態では、本明細書で開示された方法は、そのような薬学的に許容可能な塩を投与することによって疾患を処置する方法を含んでいる。いくつかの実施形態では、本明細書で開示された方法は、そのような薬学的に許容可能な塩を医薬組成物として投与することによって疾患を処置する方法を含んでいる。
いくつかの実施形態において、本明細書に記載される化合物は溶媒和物として存在する。本発明は、そのような溶媒和物を投与することによって疾患を処置する方法を提供する。本発明は、そのような溶媒和物を医薬組成物として投与することによって疾患を処置する方法をさらに提供する。
一般的に、溶媒和形態は、本明細書で提供される化合物および方法の目的のため、非溶媒和形態と同等であるとみなされる。
いくつかの実施形態において、本明細書に記載される化合物は多形体として存在する。本発明は、そのような多形体を投与することによって疾患を処置する方法を提供する。本発明は、そのような多形体を医薬組成物として投与することによって疾患を処置する方法をさらに提供する。
いくつかの実施形態において、本明細書に記載される化合物はプロドラッグ形態で存在する。本発明は、そのようなプロドラッグを投与することによって疾患を処置する方法を提供する。本発明は、そのようなプロドラッグを医薬組成物として投与することによって疾患を処置する方法を提供する。
いくつかの実施形態では、式I−IVの化合物は様々な代謝反応を受けやすい。したがって、いくつかの実施形態では、構造への適切な置換基の取り込みは、代謝経路を減らすか、最小限に抑えるか、除去する。具体的な実施形態において、代謝反応に対する芳香環の感受性を減らすまたは排除する適切な置換基は、ほんの一例として、ハロゲン、またはアルキル基である。
さらなる態様において、式I、式II、式III、または、式IVの化合物、あるいは、その薬学的に許容可能な塩および薬学的に許容可能な賦形剤を含む医薬組成物が、本明細書で提供される。
別の態様において、組織非特異性のアルカリホスファターゼ(TNAP)によって媒介された被験体の疾患を処置する方法が本明細書で提供され、該方法は、被験体に式I、式II、式III、または式IVの化合物、あるいは、その薬学的に許容可能な塩および薬学的に許容可能な賦形剤を含む医薬組成物を投与する工程を含む。いくつかの実施形態では、疾患は、内側の血管石灰化、脊柱靭帯の異所性化骨、強直症、または変形性関節症である。特定の実施形態では、疾患は動脈石灰化である。
血管石灰化を検知して測定する方法は、当該技術において周知である。いくつかの実施形態では、石灰化を測定する方法は、血管のカルシウム−リン沈着の程度を検知および測定する直接的な方法を含んでいる。
適切な投与経路は、経口投与、静脈内投与、直腸投与、エアロゾル投与、非経口投与、経眼投与、経肺投与、経粘膜投与、経皮投与、膣内投与、経耳投与、経鼻投与、および、局所投与を含むが、これらに限定されない。加えて、ほんの一例であるが、非経口送達は、くも膜下腔内、直接脳室内、腹腔内、リンパ内、および、鼻腔内の注入だけでなく、筋肉内、皮下、静脈内、髄内の注入も含む。
実施例I
<実施例I−1:5−クロロ−2−メトキシ−N−ピリジン−3−イル−ベンゼンスルホンアミド>
MS:m/z 378.1(M+H+)。
<実施例II−1:5−クロロ−2−メトキシ−N−キノリン−3−イル−ベンゼンスルホンアミド>
<実施例III−1:5−ブロモ−2−メトキシ−N−[5−(4−メトキシ−フェニル)−ピリジン−3−イル]−ベンゼンスルホンアミド>
<実施例IV−1:メチル5−(5−ブロモ−2−メトキシフェニルスルホンアミド)ニコチネート>
<実施例V−1:5−ブロモ−2−メトキシ−N−(チオフェン−3−イル)ベンゼンスルホンアミド>
MS:m/z 419.9(M+H+)。
<実施例VI−1:5−ブロモ−2−メトキシ−ピリジン−3−スルホン酸キノリン−3−イルアミド>
<実施例VII−1:5−ブロモ−2−メトキシ−N−メチル−N−(キノリン−3−イル)ベンゼンスルホンアミド>
<実施例VIII−1:5−ブロモ−2−メトキシ−N−(6−モルホニロピリジン−3−イル)ベンゼンスルホンアミド>
<実施例IX−1:5−ブロモ−N−(6−ヒドロキシキノリン−3−イル)−2−メトキシベンゼンスルホンアミド>
<実施例X−1:5−ブロモ−N−キノリン−3−イル−2−トリフルオロメトキシ−ベンゼンスルホンアミド>
<実施例XI−1:5−クロロ−N−[5−(4−メトキシ−フェニル)−ピリジン−3−イル]−2−トリフルオロメトキシ−ベンゼンスルホンアミド>
<実施例XII−1:メチル5−(5−クロロ−2−(トリフルオロメトキシ)フェニルスルホンアミド)ニコチネート>
<実施例XIII−1:5−フルオロ−2−メトキシ−N−ピリジン−3−イル−ベンゼンスルホンアミド>
黄色の固体として2.3gの5−フルオロ−2−メトキシ−N−ピリジン−3−イル−ベンゼンスルホンアミド(収率:52%)を得た。
<実施例1:TNAPを阻害する薬剤のためのアッセイ>
化合物スクリーニングライブラリ
化合物ライブラリは、NIH分子ライブラリ小分子リポジトリから提供された。化合物を、HTSに基づいた構造活性を基礎とした相関研究を補助する、密接に関連するアナログのクラスターを備えた多様な化学的空間を表わすために選択された。
分泌エピトープをタグ付けしたTNAPを含む発現プラスミドを一時的な発現用のCOS−1細胞へトランスフェクトした。培地を24時間後にOpti−MEMと取り替え、分泌タンパク質を含む無血清培地をエレクトロポレーションの60時間後に集めた。培地を1mM MgCl2および20mM ZnCl2を含むTBSに対して透析し(リン酸塩を除去するため)、0.22μm酢酸セルロースフィルタを通してろ過した。
i.TNAP比色測定法
TNAP保存液を120倍に希釈し、約12μlの希釈されたTNAP溶液を自動分注器(マトリックス、Hudson、NH)でハーフエリアボトムの96ウェルマイクロタイタープレート(Costar,Corning,NY)に分注した。ロボットリキッドハンドラーであるBiomek(商標)FX(Beckman Coulter、Fullerton、CA)で2.5μlの各化合物(10%DMSOに溶解した)をライブラリプレートから分注した。約10.5μlの基質溶液(1.19mM pNPP)を追加する前にTNAPが各化合物と相互作用できるように、プレートを室温で少なくとも1時間インキュベートした。約30分間のインキュベート後、A405nmをマイクロタイタープレートリーダーである、アナリスト(商標)HT(Molecular Devices、Sunnyvale、CA)で測定した。酵素(TNAP)および基質(pNPP)溶液の両方はジエタノールアミン(DEA)バッファー内で作製し、最終的な反応物は約1mM MgCl2および約20μM ZnCl2を包含する1M DEA−HClバッファー、約pH9.8を含む。陽性対照として使用される既知の阻害剤レバミソールおよびリン酸塩へのよい感度を維持しつつ、TNAPおよびpNPPの濃度(最終は約0.5mM)をA405nmが0.4以下になるように調節した。TNAPの1/120希釈液および約30分の固定されたインキュベーション時間で得られたKmは、0.58+0.081mMだった。
化合物の一部(4μL@10%DMSO中で100μM)を、2.5倍のアッセイバッファー(250mM DEA、pH9.8、2.5mM MgCl2、0.05mM ZnCl2)中のTNAPの800倍希釈液で調製した約8μLのTNAP希釈標準溶液とともに加えた。CDP−star基質溶液(水中で125μMを約8μl)を各ウェルに加えた。CDP−starの最終濃度は、アッセイバッファー中で測定されたKm値と等しかった。プレート(白い384−ウェル小容量Greiner 784075)を約0.5時間室温で培養し、発光シグナルをEn Visionプレートリーダー(PerkinElmer)を使用して測定した。レバミソール(最終濃度1mM)又は2%DMSOを、陽性および陰性の対照としてそれぞれ利用した。用量反応の確認を、化合物の10点の2倍段階希釈を使用して、同様の条件下で行った。
阻害剤候補、ヒトTNAP、PLAPまたはIAPの阻害選択性を決定するために、これらをマイクロタイタープレートに加え、基質pNPP(0.5mM)をさらに加え、1mM MgCl2および20μM ZnCl2を含む、1M DEA−HClバッファー、pH 9.8中で、または1M トリス−HClバッファー、pH 7.5中で、潜在的な阻害剤(0−30μM)の存在下で活性を測定した。TNAP、PLAPおよびIAP活性を適切なλA405nmである1に等しくなるように調節し、30分後に測定した。阻害剤の存在下での残留AP活性は対照の活性に対する割合として表される。阻害機構を調べるために、様々な濃度の追加阻害剤(0−30μM)の存在下での酵素活性(mA405nmmin−1として表された)対基質濃度の二重逆数プロットを構築した。1/vのY軸切片対1/[S]プロットを、x切片として図表でKiを抽出するために、その後対[I]でプロットした。yとx切片から数値は、ソフトウェアプリズム3.02(GraphPadソフトウェア、CA)を使用した、線形回帰分析によって導かれた。これらの分析はそれぞれ最適な、及び生理的なpHでKiを決定するために、基質としてpNPPを使用して1M DEA−HClバッファー、pH9.8中で、また同様に1M トリス−HClバッファー、pH7.5を使用して行った。阻害剤は、PPi(TNAPの適切で天然の基質)中で使用してpH7.4でのそれらの力学的特性に基づいて、さらに阻害剤が試験され選抜された。研究のこの部分では、ピロリン酸ナトリウム塩(99%ACS試薬、Sigma−Aldrich、St.Louis、MO)を、基質として使用した。放出されたリン酸塩の量は、Biomol Green試薬(Biomol Research Laboratories,Inc.、Plymouth Meeting、PA)を使用して測定した。最後に、生理学的な媒体での選択された阻害剤の効力を記録するために、pH7.4での式I−IV(0−30μM)の化合物によるTNAP阻害を、0.1mM pNPPの触媒作用中で、並びに濃度を増加させたNa2HPO4(0−10mM)およびピロリン酸塩(0−40mM)の存在下で調査した。
本明細書に記載の式I−IVの化合物を、Grenier1536−ウェルの透明なプレートに加えた。1.5μlの4×バッファーおよび基質混合物を、MultiDrop Combiによってプレートに加えた。その後、4.5μlのマウスまたはヒト血漿をBravoリキッドハンドラーによってウェルに加えた。4×バッファーおよび基質混合物は、400mMトリス、80μM ZnCl2、4mM MgCl2、および基質として4mMパラニトロフェノールリン酸塩(pNPP)又は8mMフェノールフタレイン一リン酸塩(PPMP)のいずれかからなる。化合物と基質を、ヒト血漿とともに密封されたアッセイプレートにおいて室温で6−30時間培養した。定常期触媒の持続時間は、血漿のホスファターゼ活性に依存した。pNPP基質については、OD380測定を採用し、血漿触媒速度を計算した。PPMP基質については、pHを調節するために、フェノールフタレイン色が濃くなってもOD555測定及び血漿触媒速度の計算前に安定したままになるよう、炭酸ナトリウムと水酸化ナトリウムから成る発色剤を加えた。2つの基質を使用して、分光測定アッセイに対して光学的に干渉する化合物をろ過した。
血管平滑筋細胞(VSMC)におけるTNAPの過剰発現が血管中膜石灰化(MVC)を引き起こすのに十分かどうか評価するために、GACIの条件付きのノックインモデルを、TNAPノックイントランスジーンのCre−媒介性発現によって生成した(図1)。ユビキタスCAG(CMV即時初期エンハンサー/ニワトリβアクチンプロモーターの融合)プロモーターの制御下にあるヒトTNAPをコードする配列を含むベクターを作製した。このコンストラクトは、Creレコンビナーゼの欠如下で過剰発現を防ぐために、プロモーターおよびトランスジーンの間にloxPが隣接する「ストップカセット」を含む。この遺伝子組み換えコンストラクトを、X染色体上のヒポキサンチンホスホリボシルトランスフェラーゼ(Hprt)遺伝子座に導入した。Hprtは、ヌクレオチド代謝に必要とされる構成的に発現するハウスキーピング酵素をコードしており、転写因子へ常時アクセスすることが可能である開いたクロマチン構造を持つゲノム領域に位置し、Hprtがその構成的な活性を可能にする。この遺伝子座へ標的化された挿入は、ランダムインテグレーション法によって引き起こされ得る任意の位置効果も克服できる。HprtALPLと名付けられたこのマウスの系統を、VSMCにおけるTNAP過剰発現の効果を検討するために使用した。HprtALPL/ALPLの雌のマウスを、VSMC特異的トランスゲリン(transgelin)プロモーター(Tagln−Cre)(Boucher P et al., Science300:329−322(2003))の制御下でCreレコンビナーゼを発現する雄のマウスと交配させた。Tagln−Creのホモ接合体の雄をHprtALPL/ALPLのホモ接合体の雌と交配させることによって、雄の子は皆[HprtALPL/Y;Tagln−Cre+/−]となり、雌は皆両方のトランスジーンのヘテロ接合体となる。
エキソビボ研究−大動脈を注意深く清潔にし、培養のために2つの部分に切断した。大動脈における異種性のために、我々は慣例的に1つの実験変数当たり8つの大動脈の部分(4つのマウス)を使用した。平滑筋細胞は小さな組織学的な変化のみで少なくとも2週間培養液において生存できる。9−12日以内に鉱化作用を引き起こすために、大動脈外植片を60,000cpm/mLの45Caおよび2.9mM NaH2PO4を含む、ダルベッコ改良イーグル培地(Dulbecco‘s Modified Eagle Medium)において培養した。この培養時間後、大動脈輪を脱水し、HClで処置し、カルシウム量を測定(librate)するために、その後それを液体シンチレーション計数によって測定した。加えて我々は公表された方法(50)により、各マウスモデルの大動脈から分離されたVSMCを培養し、また局所的なePPi濃度または全身性ePPi濃度の変化によって影響を受ける遺伝子発現の変化におけるPPiの産出及び変化を測定した。
[HprtALPL/Y;Tagln−Cre+/−]の雄又は[HprtALPL/WT;Tagln−Cre+/−]の雌のマウスおよびWT同腹子対照に、式I−IVの化合物を注入し、そのMVCの予防における有効性を評価する一方、骨格の鉱化作用上の処置または他の器官への処置による任意の副次的効果を評価した。インビボの効能の評価を、式I−IVのTNAP阻害剤の薬物代謝及び薬物動態(DMPK)特性の評価及びPK/PD相関の評価により行った。
[HprtALPL/Y;Tagln−Cre+/−]の雄又は[HprtALPL/WT;Tagln−Cre+/−]の雌のマウスおよび野生型同腹子対照に、式I−IVの化合物を注入し、試験化合物の血管中膜石灰化の予防における有効性を評価した。上記のように、血管中膜石灰化のレベルの特徴付けは、大動脈のアリザリンレッドおよびvon Kossa染色によって、またX線とμCT分析によって行った。試験化合物による骨格または他の器官の鉱化作用による任意の副次的効果を評価した。
式I−IVの化合物のマウスにおけるバイオアベイラビリティ及び血漿薬物動態の特性を、静脈内、腹腔内、皮下、筋肉内および経口投与の後に測定した。1つの投与経路ごとの1時点当たり3体の野生型マウスに様々なレベルでの投薬を行った。バイオアベイラビリティを評価するために、少なくとも1つの群は静脈内で投薬され、少なくとも1つの群は脈管外の経路で投薬される。血液は、頻繁な間隔(例えば0.25、0.5、1、2、4、6、8、12、24および48時間)で各群から採取し、試験化合物の血漿レベルは、タンデム質量分析(LC−MS/MS)と組み合わせた液体クロマトグラフィーを使用して分析した。血漿濃度時間データを、曲線下面積(AUC)を含む薬物動態のプロファイルを得るために分析した。脈管外および静脈内投与の後のAUCの比較は、化合物、クリアランス、分布容積、総暴露量および最高濃度の半減期を決定できる、時間対濃度のグラフを構築するために使用することができる。
TNAP阻害剤(例えば式I−IVの化合物、またはその薬学的に許容可能な塩)治療の安全性および/または効能のヒト臨床試験。
直線的な台形公式を使用して計算された、時点0から最後の血液採取の時点までの濃度時間曲線下面積(AUC)(AUC0−72);及び消失速度定数から算出した最終消失半減期(t1/2)。消失速度定数は、対数線形濃度時間プロットの末端の直線的な領域における連続するデータポイントの直線回帰によって評価される。薬物動態パラメーターの平均、標準偏差(SD)および変動係数(CV)を、各処置のために計算した。パラメーター平均の比率(保存されていた製剤/保存されていなかった製剤)を計算した。
TNAP阻害剤(例えば式I−IVの化合物、またはその薬学的に許容可能な塩)治療の安全性および/または効能のヒト臨床試験。
TNAP阻害剤(例えば式I−IVの化合物、またはその薬学的に許容可能な塩)治療の安全性および/または効能のヒト臨床試験。
TNAP阻害剤(例えば式I−IVの化合物、またはその薬学的に許容可能な塩)治療の安全性および/または効能のヒト臨床試験。
注入による投与に適した非経口の医薬組成物を調製するために、100mgの式I−IVの化合物または薬学的に許容可能な塩をDMSOに溶解し、その後10mlの無菌0.9%食塩水と混合した。この混合物を、注射による投与に適した投与量単位に組み込んだ。
経口送達用の医薬組成物を調製するために、400mgの式I−IVの化合物および以下の成分を良く混合し、単一の分割錠へ圧縮した。
Claims (14)
- 式(I)の化合物、あるいは、その薬学的に許容可能な塩、または溶媒和物であって、
Y1は単結合であり、
Y2は−N(R6)−であり、
L1とL2はそれぞれ単結合であり、
X1は=N−または=C(R2)−であり、
X2は=N−または=C(R3)−であり、
R1とR4は、ハロゲン、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、随意に置換されたアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたアルコキシ、ハロアルキル、ハロアルコキシ、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択され、
R2、R3、およびR5は水素であり、
R6は、水素であり、
R7とR8は独立して水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、随意に置換されたフェニルであり、あるいは、R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、
R9は、水素、随意に置換されたアルキル、ハロアルキル、随意に置換されたシクロアルキル、随意に置換されたヘテロシクロアルキル、および、随意に置換されたフェニルからなる群から選択され、および、
Aは、−C(O)−N(R7)−R8または−C(O)−O−R9である、
化合物またはその薬学的に許容可能な塩。 - 式(Ie)で示されるように、
Y1は単結合であり、Y2は−N(R6)−であり、
X2は=C(R3)−であり、
L1は単結合であり、
L2は単結合であり、および、
R6は水素である、請求項1に記載の化合物またはその薬学的に許容可能な塩。
- X1は=C(R2)−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可能な塩。
- R1とR4は、−F、−Cl、−Br、−CN、−C(O)−N(R7)−R8、−C(O)−O−R9、メチル、−OMe、−OCF3、随意に置換されたフェニル、および、随意に置換された5−または6−員環ヘテロアリールからなる群から独立して選択される、請求項1乃至3のいずれか1つに記載の化合物またはその薬学的に許容可能な塩。
- R1とR4は、−F、−Cl、−Br、−CN、−OMe、および−OCF3からなる群から独立して選択される、請求項1乃至4のいずれか1つに記載の化合物またはその薬学的に許容可能な塩。
- R1は−OMeであり、R4は−Clである、請求項5に記載の化合物またはその薬学的に許容可能な塩。
- Aは−C(O)−O−R9または、−C(O)−N(R7)−R8であり、R9は水素、メチル、エチル、プロピル、シクロヘキシル、および、フェニルから選択される、請求項1乃至6のいずれか1つに記載の化合物またはその薬学的に許容可能な塩。
- R7とR8は、それらが付けられる窒素原子と一緒に、随意に置換されたヘテロシクロアミノを形成し、随意に置換されたヘテロシクロアミノは、随意に置換されたピロリジン、随意に置換されたピペリジン、随意に置換されたモルホリン、あるいは、随意に置換されたピペラジンである、請求項7に記載の化合物またはその薬学的に許容可能な塩。
- R7は水素であり、R8は随意に置換されたアルキル、随意に置換されたシクロアルキル、または、随意に置換されたフェニルである、請求項8に記載の化合物またはその薬学的に許容可能な塩。
- 下記のいずれか1つの化合物またはその薬学的に許容可能な塩。
- 請求項1乃至10のいずれか1つの化合物またはその薬学的に許容可能な塩、および薬学的に許容可能な賦形剤を含む、医薬組成物。
- 組織非特異性のアルカリホスファターゼ(TNAP)を媒介とした被験体の疾患の処置に使用する薬剤の製造における請求項1乃至10のいずれか1つの化合物、または、その薬学的に許容可能な塩の使用。
- 疾患は、血管石灰化、脊柱靭帯の異所性骨化、強直症、または変形性関節症であり、および、血管石灰化は動脈石灰化であり、あるいは、血管石灰化は、I型糖尿病、II型糖尿病、特発性の幼児動脈石灰化(IIAC)、川崎病、肥満、または加齢に関連しており、あるいは、血管石灰化は、慢性腎疾患(慢性腎機能不全)、末期腎疾患、あるいは、透析前または透析後の尿毒症に関連している、請求項12に記載の使用。
- 疾患は病理学的石灰化であり、および、病理学的石灰化は、強直性脊椎炎、腫瘍性石灰沈着症、進行性骨化性線維形成異常症、進行性骨異所的形成、弾性線維性仮性黄色腫、強直症、変形性関節症、幼時期の一般的な動脈石灰化(GACI)、CD73の欠乏による動脈石灰化(ACDC)、Keutel症候群、腹膜の石灰化、切断患者の異所的石灰化、頸骨動脈石灰化、骨転移、人工器官の石灰化、または、骨ページェット病である、請求項12に記載の使用。
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SG11201604820XA (en) | 2014-01-14 | 2016-07-28 | Millennium Pharm Inc | Heteroaryls and uses thereof |
US10202373B2 (en) | 2014-01-14 | 2019-02-12 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
CN103755628B (zh) * | 2014-01-27 | 2015-07-29 | 河北科技大学 | 2-氨基-3-碘-5-溴吡啶的合成方法 |
WO2016054056A1 (en) * | 2014-10-01 | 2016-04-07 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Methods of treating pxe with tnap inhibitors |
AU2016291163B2 (en) * | 2015-07-08 | 2020-01-23 | Daiichi Sankyo Company, Limited | Pyridine compounds |
ITUA20161994A1 (it) * | 2016-03-24 | 2017-09-24 | Azienda Ospedaliera Univ Senese | Uso degli inibitori ddx3 come agenti anti-iperproliferativi |
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US11046710B2 (en) | 2016-12-23 | 2021-06-29 | Daiichi Sankyo Company, Limited | Sulfonamide compounds |
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Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW352384B (en) * | 1992-03-24 | 1999-02-11 | Hoechst Ag | Sulfonamido- or sulfonamidocarbonylpyridine-2-carboxamides, process for their preparation and their use as pharmaceuticals |
JP2000247949A (ja) | 1999-02-26 | 2000-09-12 | Eisai Co Ltd | スルホンアミド含有インドール化合物 |
JP4039856B2 (ja) * | 2000-02-03 | 2008-01-30 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | インテグリン発現阻害剤 |
CA2468745A1 (en) * | 2001-11-30 | 2003-06-12 | The Burnham Institute | Induction of apoptosis in cancer cells |
GB0206219D0 (en) * | 2002-03-15 | 2002-05-01 | Ferring Bv | Non-Peptide GnRH antagonists |
US20040110802A1 (en) * | 2002-08-23 | 2004-06-10 | Atli Thorarensen | Antibacterial benzoic acid derivatives |
AU2003265382A1 (en) * | 2002-08-23 | 2004-03-11 | Pharmacia & Upjohn Company Llc | Antibacterial benzoic acid derivatives |
CA2500492C (en) | 2002-11-18 | 2010-03-16 | Solomon Ungashe | Aryl sulfonamides |
AU2005266531B2 (en) * | 2004-07-28 | 2008-11-20 | F. Hoffmann-La Roche Ag | Aryl-pyridine derivatives as 11-beta-HSD1 inhibitors |
US20090142347A1 (en) * | 2004-09-29 | 2009-06-04 | The Burnham Institute For Medical Research | Tissue-Nonspecific Alkaline Phosphatase (TNAP): a Therapeutic Target for Arterial Calcification |
SE0402735D0 (sv) * | 2004-11-09 | 2004-11-09 | Astrazeneca Ab | Novel compounds |
GB0425026D0 (en) * | 2004-11-12 | 2004-12-15 | Biofocus Discovery Ltd | Compounds which bind to the active site of protein kinase enzymes |
EP1814856A1 (en) * | 2004-11-12 | 2007-08-08 | Galapagos N.V. | Nitrogen heteroaromatic compounds which bind to the active site of protein kinase enzymes |
DK1860941T3 (da) * | 2005-03-16 | 2009-03-02 | Basf Se | Biphenyl-N-(4-pyridyl)methylsufonamider |
WO2007014008A2 (en) * | 2005-07-22 | 2007-02-01 | Glaxo Group Limted | Benzenesulfonamide inhibitor of ccr2 chemokine receptor |
WO2007093599A1 (en) * | 2006-02-14 | 2007-08-23 | Basf Se | Pyridin-4 -ylmethylamides for combating pests |
WO2007129052A1 (en) * | 2006-05-03 | 2007-11-15 | Astrazeneca Ab | Pyrazole derivatives and their use as pi3k inhibitors |
JP2009535386A (ja) * | 2006-05-03 | 2009-10-01 | アストラゼネカ アクチボラグ | チアゾール誘導体および抗腫瘍剤としてのその使用 |
RU2009112719A (ru) * | 2006-09-08 | 2010-10-20 | Новартис АГ (CH) | Производные n-биарил(гетеро)арилсульфонамида, применимые в лечении заболеваний, опосредованных взаимодействием лимфоцитов |
WO2008042867A2 (en) * | 2006-09-29 | 2008-04-10 | Emiliem Inc. | Modulators of multiple kinases |
US8119693B2 (en) * | 2007-05-08 | 2012-02-21 | Sanford-Burnham Medical Research Institute | Tissue non-specific alkaline phosphatase inhibitors and uses thereof for treating vascular calcification |
US20090053192A1 (en) * | 2007-08-10 | 2009-02-26 | Burnham Institute For Medical Research | Tissue-nonspecific alkaline phosphatase (tnap) activators and uses thereof |
US8039493B2 (en) * | 2007-09-27 | 2011-10-18 | Hoffmann-La Roche Inc. | Biaryl sulfonamide derivatives |
WO2009055418A1 (en) * | 2007-10-22 | 2009-04-30 | Smithkline Beecham Corporation | Pyridosulfonamide derivatives as pi3 kinase inhibitors |
US8268834B2 (en) * | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
CA2723424A1 (en) * | 2008-05-19 | 2009-11-26 | Burnham Institute For Medical Research | Intestinal alkaline phosphatase modulators and uses thereof |
UA104147C2 (uk) * | 2008-09-10 | 2014-01-10 | Новартис Аг | Похідна піролідиндикарбонової кислоти та її застосування у лікуванні проліферативних захворювань |
US20100137313A1 (en) * | 2008-10-03 | 2010-06-03 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
WO2010130638A1 (en) * | 2009-05-14 | 2010-11-18 | Evotec Ag | Sulfonamide compounds, pharmaceutical compositions and uses thereof |
NZ596302A (en) * | 2009-05-15 | 2014-01-31 | Novartis Ag | Aryl pyridine as aldosterone synthase inhibitors |
KR101712035B1 (ko) * | 2009-06-29 | 2017-03-03 | 아지오스 파마슈티컬스 아이엔씨. | 치료용 화합물 및 조성물 |
FR2970967B1 (fr) | 2011-01-27 | 2013-02-15 | Pf Medicament | Derives de type azaindazole ou diazaindazole comme medicament |
WO2013126608A1 (en) | 2012-02-22 | 2013-08-29 | Sanford-Burnham Medical Research Institute | Sulfonamide compounds and uses as tnap inhibitors |
WO2016054056A1 (en) * | 2014-10-01 | 2016-04-07 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Methods of treating pxe with tnap inhibitors |
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CN104334527A (zh) | 2015-02-04 |
CN104334527B (zh) | 2017-05-24 |
WO2013126608A1 (en) | 2013-08-29 |
EP2817292A4 (en) | 2015-08-26 |
JP6544545B2 (ja) | 2019-07-17 |
US20160355479A1 (en) | 2016-12-08 |
US9458147B2 (en) | 2016-10-04 |
HK1203958A1 (en) | 2015-11-06 |
RU2627701C2 (ru) | 2017-08-10 |
US10370333B2 (en) | 2019-08-06 |
JP2015508102A (ja) | 2015-03-16 |
KR102083041B1 (ko) | 2020-05-27 |
BR112014020773A2 (pt) | 2020-10-27 |
AU2013222345B2 (en) | 2017-09-07 |
KR20140129191A (ko) | 2014-11-06 |
EP2817292A1 (en) | 2014-12-31 |
EP2817292B1 (en) | 2019-12-18 |
US9884826B2 (en) | 2018-02-06 |
JP2018104434A (ja) | 2018-07-05 |
US20190010126A1 (en) | 2019-01-10 |
US20150011551A1 (en) | 2015-01-08 |
CA2865071C (en) | 2020-06-23 |
RU2014137402A (ru) | 2016-04-10 |
AU2013222345A1 (en) | 2014-09-11 |
CA2865071A1 (en) | 2013-08-29 |
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