JPWO2019038214A5

JPWO2019038214A5 -

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Publication number: JPWO2019038214A5
Application number: JP2020511322A
Authority: JP
Publication date: 2023-02-02
Anticipated expiration: 2038-08-20

Description

Ｒ^１は、
Ｈａｌ、または、
１～１０個のＣ原子を有する直線状もしくは分枝状のアルキル、これらは、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されており、かつ、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲ^５ＳＯ_２Ｒ^６－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよく、または、
３～７個のＣ原子を有する単環式もしくは二環式の環状アルキル、これらは、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されており、かつ前記環状アルキル中、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲ^５ＳＯ_２Ｒ^６－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよく、または、
３～１４個の炭素原子と０～４個のヘテロ原子（独立して、Ｎ、Ｏ、およびＳから選択される）とを含有する単環式もしくは二環式のヘテロアリール、ヘテロシクリル、アリール、または環状アルキルアリール（これらは、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されている）であり、 ^R1 is
Hal, or
linear or branched alkyl having 1 to 10 C atoms, which are unsubstituted or mono-, di- or trisubstituted by R ⁴ and 1-4 the C atoms are independently of each other O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ —, —COO— , —CONH—, —NCH _{3 CO—, —CONCH 3} _— , —C≡C—, and/or —CH═CH— groups, and/or in addition, 1 to 10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic cyclic alkyl having 3 to 7 C atoms, which are unsubstituted or monosubstituted, disubstituted or trisubstituted by R ⁴ and said cyclic alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic heteroaryl, heterocyclyl, aryl containing 3 to 14 carbon atoms and 0 to 4 heteroatoms (independently selected from N, O, and S), or cyclic alkylaryl, which are unsubstituted or monosubstituted, disubstituted, or trisubstituted by ^R4 ,

Ｒ^２は、
１～１０個のＣ原子を有する直線状または分枝状のアルキルであって、これらは、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されており、かつ前記アルキル中、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲ^５ＳＯ_２Ｒ^６－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよく、または、
３～７個のＣ原子を有する環状アルキルによって置き換えられていてもよく、前記環状アルキルは、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されており、かつ前記環状アルキル中、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲ^５ＳＯ_２Ｒ^６－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよく、または、
３～１４個の炭素原子と０～４個のヘテロ原子（独立して、Ｎ、Ｏ、およびＳから選択される）とを含有する単環式もしくは二環式のヘテロアリール、ヘテロシクリル、アリール、または環状アルキルアリール（これらは、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されている）であり、 ^R2 is
linear or branched alkyl having 1 to 10 C atoms, which are unsubstituted or mono-, di- or trisubstituted by R ⁴ and said alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
optionally substituted by a cyclic alkyl having 3 to 7 C atoms, said cyclic alkyl being unsubstituted or mono-, di- or trisubstituted by R ⁴ and said cyclic In alkyl, 1 to 4 C atoms are independently of each other O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH-, —NHCO—, —NR ⁵ SO ₂ R ⁶ -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- groups, and/or -CH=CH- groups, and/or , in addition, 1 to 10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic heteroaryl, heterocyclyl, aryl containing 3 to 14 carbon atoms and 0 to 4 heteroatoms (independently selected from N, O, and S), or cyclic alkylaryl, which are unsubstituted or monosubstituted, disubstituted, or trisubstituted by ^R4 ,

Ｒ^４は、
Ｈ、Ｒ^５、＝Ｓ、＝ＮＲ^５、＝Ｏ、ＯＨ、ＣＯＯＨ、Ｈａｌ、ＮＨ_２、ＳＯ_２ＣＨ_３、ＳＯ_２ＮＨ_２、ＣＮ、ＣＯＮＨ_２、ＮＨＣＯＣＨ_３、ＮＨＣＯＮＨ_２、ＮＯ_２、または１～１０個のＣ原子を有する直線状もしくは分枝状のアルキルであって、前記アルキルは、非置換であるか、またはＲ^５によって単置換、二置換、もしくは三置換されており、かつ前記アルキル中、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲ^５ＳＯ_２Ｒ^６－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよく、または、
３～７個のＣ原子を有する単環式もしくは二環式の環状アルキルによって置き換えられていてもよく、前記環状アルキルは、非置換であるか、またはＲ^５によって単置換、二置換、もしくは三置換されており、かつ前記環状アルキル中、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲＳＯ_２Ｒ^４－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよく、または、
３～１４個の炭素原子と０～４個のヘテロ原子（独立して、Ｎ、Ｏ、およびＳから選択される）とを含有する単環式もしくは二環式のヘテロアリール、ヘテロシクリル、アリール、または環状アルキルアリール（これらは、非置換であるか、またはＲ^５によって単置換、二置換、もしくは三置換されている）であり、 ^R4 is
H, R5, =S, = ^NR5 , =O, OH, COOH, Hal, _NH2 , ^SO2CH3 _, _SO2NH2 , CN, _CONH2 , _NHCOCH3 _, _NHCONH2 , _NO2 , or ₁ linear or branched alkyl having ∼10 C atoms, said alkyl being unsubstituted or monosubstituted, disubstituted or trisubstituted by R ⁵ and said alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
may be substituted by monocyclic or bicyclic cyclic alkyl having 3 to 7 C atoms, said cyclic alkyl being unsubstituted or monosubstituted, disubstituted or trisubstituted by R ⁵ ; substituted and in said cyclic alkyl 1 to 4 C atoms are independently of each other O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO -, -NRSO ₂ R ⁴ -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- groups, and/or -CH=CH- groups. and/or in addition, 1 to 10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic heteroaryl, heterocyclyl, aryl containing 3 to 14 carbon atoms and 0 to 4 heteroatoms (independently selected from N, O, and S), or cyclic alkylaryl, which are unsubstituted or monosubstituted, disubstituted, or ^{trisubstituted} by R5 ,

本発明は、好ましくは、式Ｉ、式中
Ｒ^１は、
１～１０個のＣ原子を有する直線状または分枝状のアルキルであり、ここで、非置換であるか、またはＲ^４によって単置換、二置換、もしくは三置換されており、かつ前記アルキル中、１～４個のＣ原子は、相互に独立して、Ｏ、Ｓ、ＳＯ、ＳＯ_２、ＮＨ、ＮＣＨ_３、－ＯＣＯ－、－ＮＨＣＯＮＨ－、－ＮＨＣＯ－、－ＮＲ^５ＳＯ_２Ｒ^６－、－ＣＯＯ－、－ＣＯＮＨ－、－ＮＣＨ_３ＣＯ－、－ＣＯＮＣＨ_３－、－Ｃ≡Ｃ－基、および／または－ＣＨ＝ＣＨ－基によって置き換えられていてもよいし、および／または、加えて、１～１０個のＨ原子は、Ｆおよび／またはＣｌによって置き換えられていてもよい、または、
以下の構造体：

の１つである、ここで前記構造体は、非置換であるか、またはＲ^４で単置換、二置換、もしくは三置換されており、
かつ式中Ｑ、Ｙ、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、およびＲ^６は、上に開示されたとおりの意味を有する、
で表される化合物に関する。 The present invention preferably relates to formula I, wherein R ¹ is
linear or branched alkyl having 1 to 10 C atoms , wherein it is unsubstituted or mono-, di- or trisubstituted by R ⁴ and said alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
The following structs:

wherein said structure is unsubstituted or mono-, di-, or tri-substituted at ^R4 ;
and wherein Q, Y, ^R2 , R3 ^, ^R4 , ^R5 , and ^R6 have the meanings as disclosed above;
Relating to the compound represented by

Claims

Formula I,

wherein Q and Y are independently CH or N;
^R1 is
Hal, or
linear or branched alkyl having 1 to 10 C atoms, which are unsubstituted or mono-, di- or trisubstituted by R ⁴ and 1-4 the C atoms are independently of each other O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ —, —COO— , —CONH—, —NCH _{3 CO—, —CONCH 3} _— , —C≡C—, and/or —CH═CH— groups, and/or in addition, 1 to 10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic cyclic alkyl having 3 to 7 C atoms, which are unsubstituted or monosubstituted, disubstituted or trisubstituted by R ⁴ and said cyclic alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic heteroaryl, heterocyclyl, aryl containing 3 to 14 carbon atoms and 0 to 4 heteroatoms (independently selected from N, O, and S), or cyclic alkylaryl, which are unsubstituted or monosubstituted, disubstituted, or trisubstituted by ^R4 ,
^R2 is
linear or branched alkyl having 1 to 10 C atoms, which are unsubstituted or mono-, di- or trisubstituted by R ⁴ and said alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
optionally substituted by a cyclic alkyl having 3 to 7 C atoms, said cyclic alkyl being unsubstituted or mono-, di- or trisubstituted by R ⁴ and said cyclic In alkyl, 1 to 4 C atoms are independently of each other O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH-, —NHCO—, —NR ⁵ SO ₂ R ⁶ -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- groups, and/or -CH=CH- groups, and/or , in addition, 1 to 10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic heteroaryl, heterocyclyl, aryl containing 3 to 14 carbon atoms and 0 to 4 heteroatoms (independently selected from N, O, and S), or cyclic alkylaryl, which are unsubstituted or monosubstituted, disubstituted, or trisubstituted by ^R4 ,
R ³ is linear or branched alkyl or O-alkyl with 1 to 6 C atoms or cyclic alkyl with 3 to 6 C atoms, which are unsubstituted or H, ═S, ═NH, ═O, OH, cyclic alkyl with 3 to 6 C atoms, COOH, Hal, NH ₂ , SO ₂ CH ₃ , SO ₂ NH ₂ , CN, CONH ₂ , monosubstituted, _{disubstituted} , or trisubstituted with _NHCOCH3 , _NHCONH2 , or NO2;
^R4 is
H, R5, =S, = ^NR5 , =O, OH, COOH, Hal, _NH2 , ^SO2CH3 _, _SO2NH2 , CN, _CONH2 , _NHCOCH3 _, _NHCONH2 , _NO2 , or ₁ linear or branched alkyl having ∼10 C atoms, said alkyl being unsubstituted or monosubstituted, disubstituted or trisubstituted by R ⁵ and said alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
may be substituted by monocyclic or bicyclic cyclic alkyl having 3 to 7 C atoms, said cyclic alkyl being unsubstituted or monosubstituted, disubstituted or trisubstituted by R ⁵ ; substituted and in said cyclic alkyl 1 to 4 C atoms are independently of each other O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO -, -NRSO ₂ R ⁴ -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- groups, and/or -CH=CH- groups. and/or in addition, 1 to 10 H atoms may be replaced by F and/or Cl, or
monocyclic or bicyclic heteroaryl, heterocyclyl, aryl containing 3 to 14 carbon atoms and 0 to 4 heteroatoms (independently selected from N, O, and S), or cyclic alkylaryl, which are unsubstituted or monosubstituted, disubstituted, or ^{trisubstituted} by R5 ,
R ⁵ and R ⁶ are each independently H, =S, =NH, ₌ O, OH, COOH, Hal, _NH2 , _SO2CH3 _, _SO2NH2 , CN, _CONH2 , _NHCOCH3 , NHCONH ₂ , NO ₂ , and linear or branched alkyl having 1 to 10 C atoms, wherein 1 to 4 C atoms are independently , O, S, SO, SO ₂ , NH, NCH ₃ , —OCO-, —NHCONH-, —NHCO-, —COO-, —CONH-, —NCH _{3 CO-, —CONCH 3} _— , —C may be replaced by ≡C- groups and/or -CH=CH- groups and/or in addition 1 to 10 H atoms may be replaced by F and/or Cl often,
Hal is F, Cl, Br, or I;
and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, and mixtures thereof in all ratios.

wherein R ¹ is
linear or branched alkyl having 1 to 10 C atoms , wherein it is unsubstituted or mono-, di- or trisubstituted by R ⁴ and said alkyl 1 to 4 C atoms in which, independently of each other, are O, S, SO, SO ₂ , NH, NCH ₃ , —OCO—, —NHCONH—, —NHCO—, —NR ⁵ SO ₂ R ⁶ may be replaced by -, -COO-, -CONH-, -NCH _{3 CO-, -CONCH 3} _- , -C≡C- and/or -CH=CH- groups, and/or Additionally, 1-10 H atoms may be replaced by F and/or Cl, or
The following structs:

wherein said structure is unsubstituted or mono-, di-, or tri-substituted at ^R4 ;
and wherein Q, Y, ^R2 , R3 ^, ^R4 , R5 and ^R6 have the meanings as disclosed in claim ¹ ,
A compound according to claim 1, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, and mixtures thereof in all ratios.