RU2012149216A - Новое производное гидроксамовой кислоты - Google Patents

Новое производное гидроксамовой кислоты Download PDF

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RU2012149216A
RU2012149216A RU2012149216/04A RU2012149216A RU2012149216A RU 2012149216 A RU2012149216 A RU 2012149216A RU 2012149216/04 A RU2012149216/04 A RU 2012149216/04A RU 2012149216 A RU2012149216 A RU 2012149216A RU 2012149216 A RU2012149216 A RU 2012149216A
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RU2575129C2 (ru
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Хадзиме ТАКАСИМА
Риса ЦУРУТА
Тецуя ЯБУУТИ
Юсуке ОКА
Хироки УРАБЕ
Еитиро СУГА
Масато Такахаси
Фумито УНЕУТИ
Хиронори КОЦУБО
Мунео СЕДЗИ
Ясуко КАВАГУТИ
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Тайсо Фармасьютикал Ко., Лтд.
Тояма Кемикал Ко., Лтд.
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    • C07C233/82Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/83Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
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    • A61K31/166Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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  • Plural Heterocyclic Compounds (AREA)

Abstract

1. Соединение, соответствующее следующей общей формуле [1], или его фармацевтически приемлемая соль:[Химическая формула 1]где Rи Rявляются одинаковыми или отличаются и каждый из них представляет собой атом водорода, Cалкильную группу, Сциклоалкильную группу или Cалкоксигруппу (Cалкильная группа, Cалкоксигруппа и Сциклоалкильная группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, Cциклоалкильной группы, CалкоксигруппыСциклоалкоксигруппы, аминогруппы, Cалкиламиногруппы, ди(Cалкил)аминогруппы, -N(R)COR, -N(R)SOR, цианогруппы, карбоксигруппы, карбамоильной группы, -CON(R)(R), -SON(R)R), Cалкилтиогруппы, Cалкилалкилсульфонильной группы, арилоксигруппы, арильной группы и гетероциклической группы"),R, R, Rи Rявляются одинаковыми или отличаются, и каждый из них представляет собой атом водорода или Салкильную группу,Rи R, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,Rпредставляет собой атом водорода или Салкильную группу (Cалкильная группа может быть замещена 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, Cалкоксигруппы, Сциклоалкоксигруппы, аминогруппы, Cалкиламиногруппы и ди(Cалкил)аминогруппы"),Rпредставляет собойатом водорода,гидроксигруппу,Cалкоксигруппу,Cциклоалкоксигруппу,аминогруппу,Салкиламиногруппу,ди(Cалкил)аминогруппу,Cалкильную группу, Cциклоалкильную группу(Cалкильная группа и Cциклоалкильная группа мо�

Claims (25)

1. Соединение, соответствующее следующей общей формуле [1], или его фармацевтически приемлемая соль:
[Химическая формула 1]
Figure 00000001
где R1 и R2 являются одинаковыми или отличаются и каждый из них представляет собой атом водорода, C1-6алкильную группу, С3-8циклоалкильную группу или C1-6алкоксигруппу (C1-6алкильная группа, C1-6алкоксигруппа и С3-8циклоалкильная группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, C3-8циклоалкильной группы, C1-6алкоксигруппы, С3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R11)COR12, -N(R11)SO2R12, цианогруппы, карбоксигруппы, карбамоильной группы, -CON(R13)(R14), -SO2N(R13)(R14), C1-6алкилтиогруппы, C1-6алкилалкилсульфонильной группы, арилоксигруппы, арильной группы и гетероциклической группы"),
R11, R12, R13 и R14 являются одинаковыми или отличаются, и каждый из них представляет собой атом водорода или С1-6алкильную группу,
R13 и R14, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
R3 представляет собой атом водорода или С1-6алкильную группу (C1-6алкильная группа может быть замещена 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, C1-6алкоксигруппы, С3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы и ди(C1-6 алкил)аминогруппы"),
R4 представляет собой
атом водорода,
гидроксигруппу,
C1-6алкоксигруппу,
C3-8циклоалкоксигруппу,
аминогруппу,
С1-6алкиламиногруппу,
ди(C1-6алкил)аминогруппу,
C1-6алкильную группу, C3-8циклоалкильную группу
(C1-6алкильная группа и C3-8циклоалкильная группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, C3-8циклоалкильной группы, C1-6алкоксигруппы, C3-8циклоалкоксигруппы, аминогруппы, С1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R41)COR42, -N(R41)SO2R42, цианогруппы, карбоксигруппы, -CON(R43)(R44), -SO2N(R43)(R44), С1-6алкилтиогруппы, C1-6алкилалкилсульфонильной группы, арильной группы, арилоксигруппы и гетероциклической группы (арильная группа, арилоксигруппа, и гетероциклическая группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, C1-6алкильной группы, C3-8циклоалкильной группы, бензильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, C2-8алкоксиалкильной группы, гидроксигруппы, C1-6алкоксигруппы, C3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R45)COR46, -N(R45)SO2R46, цианогруппы, карбоксигруппы, -CON(R47)(R48), -SO2N(R47)(R48), C1-6алкилтиогруппы и С1-6алкилсульфонильной группы")),
арильную группу или гетероциклическую группу
(арильная группа и гетероциклическая группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, C1-6алкильной группы, C3-8циклоалкильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, С2-8алкоксиалкильной группы, гидроксигруппы, C1-6алкоксигруппы, C3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R45)COR46, -N(R45)SO2R46, цианогруппы, карбоксигруппы, -CON(R47)R48), -SO2N(R47)(R48), алкилтиогруппы и C1-6алкилсульфонильной группы"),
R41, R42, R43, R44, R45, R46, R47 и R48 являются одинаковыми или отличаются, и каждый из них представляет собой атом водорода или C1-6алкильную группу,
R43 и R44, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
R47 и R48, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
R3 и R4, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
A1 представляет собой двухвалентную арильную группу, двухвалентную гетероциклическую группу или C3-8циклоалкиленовую группу (двухвалентная арильная группа, двухвалентная гетероциклическая группа и C3-8циклоалкиленовая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из следующей группы заместителей Ra):
группа заместителей Ra состоит из атома галогена, гидроксигруппы, аминогруппы (аминогруппа может быть замещена C2-6алканоильной группой или одной или двумя С1-6алкильными группами), карбоксигруппы, карбамоильной группы, C1-6алкильной группы, C3-8циклоалкильной группы, С2-6алкенильной группы и C1-6алкоксигруппы (C1-6алкильная группа, C3-8циклоалкильная группа, С1-6алкенильная группа и C1-6алкоксигруппа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы, карбоксигруппы, C1-6алкиламинокарбонильной группы и С1-6алкоксикарбонильной группы"),
L представляет собой -C≡C-, -C≡C-C≡C-, -C≡C-(CH2)m-O-, -CH=CH-, -CH=CH-C≡C-, -C≡C-CH=CH-, -O-, -S-, -NR5-, -CONR5-, -NR5CO-, двухвалентную гетероциклическую группу, -(CH2)m-NR5-, -(CH2)m-O-, -NR5-(CH2)m-, -O-(СН2)m-, -ON=CH-, C1-4алкиленовую группу или связь,
R5 представляет собой атом водорода, C1-6алкильную группу, C3-8циклоалкильную группу или арильную группу,
m обозначает 1, 2 или 3,
A2 представляет собой двухвалентную арильную группу, двухвалентную гетероциклическую группу, двухвалентную частично насыщенную конденсированную полициклическую углеводородную кольцевую группу, С3-8циклоалкиленовую группу, C3-8циклоалкениленовую группу, C1-4алкиленовую группу или С2-4алкениленовую группу (двухвалентная арильная группа, двухвалентная гетероциклическая группа, двухвалентная частично насыщенная конденсированная полициклическая углеводородная кольцевая группа, C3-8циклоалкениленовая группа, С3-8циклоалкиленовая группа, C1-4алкиленовая группа и C2-4алкениленовая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из следующей группы заместителей Rb):
группа заместителей Rb состоит из атома галогена, необязательно защищенной гидроксигруппы, меркаптогруппы, цианогруппы, нитрогруппы, необязательно защищенной аминогруппы, необязательно защищенной формильной группы, необязательно защищенной карбоксигруппы, карбамоильной группы, сульфогруппы, уреидогруппы, гуанидидогруппы, C1-6алкильной группы, C3-8циклоалкильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, C1-6алкоксигруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, C1-6алкоксикарбонильной группы, C2-6алканоильной группы и арильной группы,
W представляет собой R6-X1-, R6-X2-Y1-X1-, R6-X4-Y1-X2-Y3-X3-, Q-X1-Y2-X3- или Q-X1-Y1-X2-Y3-X3-,
Y2 представляет собой -O-, -NR7-, -CO-, -NR7CO-, -CONR7-, -S(O)n-, -OCO-, -COO-, -NR7SO2-, -SO2-NR7-, -OCOO-, -OCONR7-, -NR7CONR8- или связь,
Y1 и Y3 являются одинаковыми или отличаются и каждый из них представляет собой -O-, -NR7-, -CO-, -NR7CO-, -CONR7-, -S(O)n-, -OCO-, -COO-, -NR7SO2-, -SO2NR7-, -OCOO-, -OCONR7- или -NR7CONR8-,
n обозначает 0, 1 или 2,
X1 и X3 являются одинаковыми или отличаются и каждый из них представляет собой С1-10алкиленовую группу, С2-10алкениленовую группу, С2-10алкиниленовую группу, C3-8циклоалкиленовую группу, -C1-6алкилен-С3-8циклоалкилен-C1-6-алкилен- (С1-10алкиленовая группа, С2-10алкениленовая группа, С2-10алкиниленовая группы, C3-8циклоалкиленовая группа, -C1-6алкилен-С3-8циклоалкилен-C1-6-алкилен- могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже) или связь,
X2 и X4 являются одинаковыми или отличаются и каждый из них представляет собой С1-10алкиленовую группу, С2-10алкениленовую группу, С2-10алкиниленовую группу или -C1-6алкилен-С3-8циклоалкилен-C1-6-алкилен- (С1-10алкиленовая группа, С2-10алкениленовая группа, С2-10алкиниленовая группы и -C1-6алкилен-С3-8циклоалкилен-C1-6-алкилен- могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
Q представляет собой C3-8циклоалкильную группу, арильную группу или гетероциклическую группу (C3-8циклоалкильная группа, арильная группа и гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже, и в гетероциклической группе различные атомы углерода на кольце могут быть соединены мостиковой связью с C1-6алкиленовой группой или -C1-6алкилен-O-C1-6алкиленом-),
R6 представляет собой атом водорода, атома галогена, необязательно защищенную гидроксигруппу, меркаптогруппу, цианогруппу, нитрогруппу, необязательно защищенную аминогруппу, необязательно защищенную формильную группу, необязательно защищенную карбоксигруппу, карбамоильную группу, сульфогруппу, необязательно защищенную фосфатную группу, уреидогруппу, гуанидидогруппу, R7-O-NR8-CO-, R8-ON=CR9-, R8-ON=CR9-NH-, R7-O-NR8-CH=N-, (R7)(R8)N-N=CH-, R8-O-NR8-, N≡C-NR8- или C1-6алкоксигруппу (C1-6алкоксигруппа может быть замещена 1-3 гидроксигруппами),
R7 и R8 являются одинаковыми или отличаются и каждый из них представляет собой атом водорода, C1-6алкильную группу, С3-8циклоалкильную группу, арильную группу или гетероциклическую группу (C1-6алкильная группа, С3-8циклоалкильная группа, арильная группа и гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
R9 представляет собой атом водорода, C1-6алкильную группу, C3-8циклоалкильную группу, аминогруппу или C1-6алкиламиногруппу, и
группа заместителей Rc состоит из атома галогена, гидроксигруппы, цианогруппы, нитрогруппы, аминогруппы (аминогруппа может быть замещена C2-6алканоильной группой или одной или двумя C1-6алкильными группами), карбоксигруппы, карбамоильной группы, уреидогруппы, гуанидидогруппы, C1-6алкильной группы (C1-6алкильная группа может быть замещена гетероциклической группой), C1-6гидроксиалкильной группы, C1-6галоалкильной группы, C3-8циклоалкильной группы, C1-6алкоксигруппы (C1-6алкоксигруппа может быть замещена 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из гидроксигруппы, атома галогена, C3-8циклоалкильной группы, C1-6алкоксигруппы, арильной группы и гетероциклической группы), C3-8циклоалкоксигруппы, C1-6алкоксикарбонильной группы, C1-6алкоксикарбониламиногруппы, С1-6алканоильной группы, C1-6алкилсульфонильной группы, C1-6алкилтиогруппы, арильной группы, гетероциклической группы (арильная группа и гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, цианогруппы, нитрогруппы, аминогруппы, карбоксигруппы и C1-6алкильной группы"), C1-6алкилиденовой группы (C1-6алкилиденовая группа может быть замещена C1-6алкоксигруппой), С3-8циклоалкилиденовой группы, моноциклической насыщенной гетероциклиденовой группы (моноциклическая насыщенная гетероциклиденовая группа может быть замещена 1-2 C1-6алкильными группами) и гидроксиаминокарбонильной группы.
2. Соединение, соответствующее следующей общей формуле [1], или его фармацевтически приемлемая соль по п.1:
[Химическая формула 2]
Figure 00000002
где R1 и R2 являются одинаковыми или отличаются и каждый из них представляет собой атом водорода, C1-6алкильную группу, С3-8циклоалкильную группу или C1-6алкоксигруппу (C1-6алкильная группа, C1-6 алкоксигруппа и С3-8циклоалкильная группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, C3-8циклоалкильной группы, C1-6алкоксигруппы, С3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R11)COR12, -N(R11)SO2R12, цианогруппы, карбоксигруппы, карбамоильной группы, -CON(R13)(R14), -SO2N(R13)(R14), C1-6алкилтиогруппы, C1-6алкилсульфонильной группы, арилоксигруппы, арильной группы и гетероциклической группы"),
R11, R12, R13 и R14 являются одинаковыми или отличаются, и каждый из них представляет собой атом водорода или С1-6алкильную группу,
R13 и R14, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
R3 представляет собой атом водорода или С1-6алкильную группу (C1-6алкильная группа может быть замещена 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, C1-6алкоксигруппы, С3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы и ди(C1-6алкил)аминогруппы"),
R4 представляет собой
атом водорода,
гидроксигруппу,
C1-6алкоксигруппу,
C3-8циклоалкоксигруппу,
аминогруппу,
С1-6алкиламиногруппу,
ди(C1-6алкил)аминогруппу,
C1-6алкильную группу, C3-8циклоалкильную группу
(C1-6алкильная группа и C3-8циклоалкильная группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из
"атома галогена, гидроксигруппы, C3-8циклоалкильной группы, C1-6алкоксигруппы, C3-8циклоалкоксигруппы, аминогруппы, С1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R41)COR42, -N(R41)SO2R42, цианогруппы, карбоксигруппы, -CON(R43)(R44), -SO2N(R43)(R44), С1-6алкилтиогруппы, C1-6алкилсульфонильной группы, арильной группы, арилоксигруппы и гетероциклической группы (арильная группа, арилоксигруппа и гетероциклическая группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, C1-6алкильной группы, C3-8циклоалкильной группы, бензильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, C2-8алкоксиалкильной группы, гидроксигруппы, C1-6алкоксигруппы, C3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R45)COR46, -N(R45)SO2R46, цианогруппы, карбоксигруппы, -CON(R47)(R48), -SO2N(R47)(R48), C1-6алкилтиогруппы и С1-6алкилсульфонильной группы")),
арильную группу или гетероциклическую группу
(арильная группа и гетероциклическая группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, C1-6алкильной группы, C3-8циклоалкильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, С2-8алкоксиалкильной группы, гидроксигруппы, C1-6алкоксигруппы, C3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R45)COR46, -N(R45)SO2R46, цианогруппы, карбоксигруппы, -CON(R47)R48), -SO2N(R47)(R48), C1-6алкилтиогруппы и C1-6алкилсульфонильной группы"),
R41, R42, R43, R44, R45, R46, R47 и R48 являются одинаковыми или отличаются, и каждый из них представляет собой атом водорода или C1-6алкильную группу,
R43 и R44, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
R47 и R48, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
R3 и R4, вместе с атомом азота, к которому они присоединены, могут образовывать насыщенное или ненасыщенное 5- или 6-членное кольцо, которое может дополнительно содержать один или несколько атомов азота, атомов кислорода или атомов серы,
A1 представляет собой двухвалентную арильную группу, двухвалентную гетероциклическую группу или C3-8циклоалкиленовую группу (двухвалентная арильная группа, двухвалентная гетероциклическая группа и C3-8циклоалкиленовая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из следующей группы заместителей Ra):
группа заместителей Ra состоит из атома галогена, гидроксигруппы, аминогруппы (аминогруппа может быть замещена C2-6алканоильной группой или одной или двумя С1-6алкильными группами), карбоксигруппы, карбамоильной группы, C1-6алкильной группы, C3-8циклоалкильной группы, С2-6алкенильной группы и C1-6алкоксигруппы (C1-6алкильная группа, C3-8циклоалкильная группа, С2-6алкенильная группа и C1-6алкоксигруппа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы, карбоксигруппы, C1-6алкиламинокарбонильной группы и С1-6алкоксикарбонильной группы"),
L представляет собой -C≡C-, -C≡C-C≡C-, -O-, -S-, -NR5-, -CONR5-, -NR5CO-, двухвалентную гетероциклическую группу, -(CH2)m-NR5-, -(CH2)m-O-, -NR5-(CH2)m-, -O-(СН2)m-, -ON=CH-, C1-4алкиленовую группу или связь,
R5 представляет собой атом водорода, C1-6алкильную группу, C3-8циклоалкильную группу или арильную группу,
m обозначает 1, 2 или 3,
A2 представляет собой двухвалентную арильную группу, двухвалентную гетероциклическую группу, двухвалентную частично насыщенную конденсированную полициклическую углеводородную кольцевую группу, С3-8циклоалкиленовую группу, C1-4алкиленовую группу или С2-4алкениленовую группу (двухвалентная арильная группа, двухвалентная гетероциклическая группа, двухвалентная частично насыщенная конденсированная полициклическая углеводородная кольцевая группа, C3-8циклоалкиленовая группа, C1-4алкиленовая группа и C2-4алкениленовая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из следующей группы заместителей Rb):
группа заместителей Rb состоит из атома галогена, необязательно защищенной гидроксигруппы, меркаптогруппы, цианогруппы, нитрогруппы, необязательно защищенной аминогруппы, необязательно защищенной формильной группы, необязательно защищенной карбоксигруппы, карбамоильной группы, сульфогруппы, уреидогруппы, гуанидидогруппы, C1-6алкильной группы, C3-8циклоалкильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, C1-6алкоксигруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, C1-6алкоксикарбонильной группы, C2-6алканоильной группы и арильной группы,
W представляет собой R6-X1-, R6-X2-Y1-X1-, R6-X4-Y1-X2-Y3-X3-, Q-X1-Y2-X3- или Q-X1-Y1-X2-Y3-X3-,
Y2 представляет собой -O-, -NR7-, -CO-, -NR7CO-, -CONR7-, -S(O)n-, -OCO-, -COO-, -NR7SO2-, -SO2-NR7-, -OCOO-, -OCONR7-, -NR7CONR8- или a представляет собой связь,
Y1 и Y3 являются одинаковыми или отличаются и каждый из них представляет собой -O-, -NR7-, -CO-, -NR7CO-, -CONR7-, -S(O)n-, -OCO-, -COO-, -NR7SO2-, -SO2NR7-, -OCOO-, -OCONR7- или -NR7CONR8-,
n обозначает 0, 1 или 2,
X1 и X3 являются одинаковыми или отличаются и каждый из них представляет собой С1-10алкиленовую группу, С2-10алкениленовую группу, С2-10алкиниленовую группу, (С1-10алкиленовая группа, С2-10алкениленовая группа, С2-10алкиниленовая группы могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже) или связь,
X2 и X4 являются одинаковыми или отличаются и каждый из них представляет собой С1-10алкиленовую группу, С2-10алкениленовую группу, С2-10алкиниленовую группу, -C1-6алкилен-С3-8циклоалкилен-C1-6алкилен- (С1-10алкиленовая группа, С2-10алкениленовая группа, С2-10алкиниленовая группы и -C1-6алкилен-С3-8циклоалкилен-C1-6-алкилен- могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
Q представляет собой C3-8циклоалкильную группу, арильную группу или гетероциклическую группу (C3-8циклоалкильная группа, арильная группа и гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
R6 представляет собой атом водорода, атома галогена, необязательно защищенную гидроксигруппу, меркаптогруппу, цианогруппу, нитрогруппу, необязательно защищенную аминогруппу, необязательно защищенную формильную группу, необязательно защищенную карбоксигруппу, карбамоильную группу, сульфогруппу, необязательно защищенную фосфатную группу, уреидогруппу, гуанидидогруппу, R7-O-NR8-CO-, R8-ON=CR9-, R8-ON=CR9-NH-, R7-O-NR8-CH=N-, (R7)(R8)N-N=CH-, R8-O-NR8- или N≡C-NR8-,
R7 и R8 являются одинаковыми или отличаются и каждый из них представляет собой атом водорода, C1-6алкильную группу, С3-8циклоалкильную группу, арильную группу или гетероциклическую группу (C1-6алкильная группа, С3-8циклоалкильная группа, арильная группа и гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
R9 представляет собой атом водорода, C1-6алкильную группу, C3-8циклоалкильную группу, аминогруппу или C1-6алкиламиногруппу, и
группа заместителей Rc состоит из атома галогена, гидроксигруппы, цианогруппы, нитрогруппы, аминогруппы (аминогруппа может быть замещена C2-6алканоильной группой или одной или двумя C1-6алкильными группами), карбоксигруппы, карбамоильной группы, уреидогруппы, гуанидидогруппы, C1-6алкильной группы (C1-6алкильная группа может быть замещена гетероциклической группой), C1-6гидроксиалкильной группы, C1-6галоалкильной группы, C3-8циклоалкильной группы, C1-6алкоксигруппы (C1-6алкоксигруппа может быть замещена 1-3 гидроксигруппами), C3-8циклоалкоксигруппы, C1-6алкоксикарбонильной группы, C1-6алкоксикарбониламиногруппы, С2-6алканоильной группы, C1-6алкилсульфонильной группы, C1-6алкилтиогруппы, арильной группы, гетероциклической группы (арильная группа и гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, цианогруппы, нитрогруппы, аминогруппы, карбоксигруппы и C1-6алкильной группы").
3. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где R1 представляет собой атом водорода или C1-6алкильную группу (С1-6алкильная группа может быть замещена 1-3 одинаковыми или различными атомами галогена).
4. Соединение или его фармацевтически приемлемая соль по п.3, где R1 представляет собой C1-6алкильную группу (С1-6алкильная группа может быть замещена 1-3 одинаковыми или различными атомами галогена).
5. Соединение или его фармацевтически приемлемая соль по п.4, где R1 представляет собой метильную группу.
6. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где R2 представляет собой атом водорода.
7. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где R2 представляет собой метильную группу.
8. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где
R3 представляет собой атом водорода, и
R4 представляет собой C1-6алкильную группу (C1-6алкильная группа может быть замещена фенильной группой или моноциклической ароматической гетероциклической группой (фенильная группа и моноциклическая ароматическая гетероциклическая группа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, C1-6алкильной группы, C3-8циклоалкильной группы, C1-6галоалкильной группы, C1-6гидроксиалкильной группы, С2-8алкоксиалкильной группы, гидроксигруппы, C1-6алкоксигруппы, С3-8циклоалкоксигруппы, аминогруппы, C1-6алкиламиногруппы, ди(C1-6алкил)аминогруппы, -N(R45)COR46, -CON(R47)(R48)")).
9. Соединение или его фармацевтически приемлемая соль по п.8, где R3 представляет собой атом водорода и R4 представляет собой метильную группу.
10. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где A1 представляет собой фениленовую группу (фениленовая группа может быть замещена 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы и C1-6алкильной группы").
11. Соединение или его фармацевтически приемлемая соль по п.10, где A1 представляет собой фениленовую группу.
12. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где L представляет собой -C≡C-, -C≡C-C≡C-, -CH=CH-, -CH=CH-C≡C-, -C≡C-CH=CH-, этиленовую группу или связь.
13. Соединение или его фармацевтически приемлемая соль по п.12, где L представляет собой связь или -C≡C-.
14. Соединение или его фармацевтически приемлемая соль по п.13, где L представляет собой связь.
15. Соединение или его фармацевтически приемлемая соль по п.13, где L представляет собой -C≡C-.
16. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где
A2 представляет собой двухвалентную арильную группу (двухвалентная арильная группа может быть замещена 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы и С1-6алкильной группы"), двухвалентную моноциклическую ароматическую гетероциклическую группу (двухвалентная моноциклическая ароматическая гетероциклическая группа содержит, в качестве составляющих кольцо атомов, любые 1-3 атома, выбранных из атома азота, атома кислорода и атома серы, и может быть замещена 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы и С1-6алкильной группы"), двухвалентную конденсированную кольцевую ароматическую гетероциклическую группу или двухвалентную конденсированную кольцевую гетероциклическую группу, имеющую частично насыщенный моноцикл (двухвалентная конденсированная кольцевая ароматическая гетероциклическая группа и двухвалентная конденсированная кольцевая гетероциклическая группа, имеющая частично насыщенный моноцикл, содержат, в качестве образующего кольцо атома, любые 1-4 атома, выбранных из атома азота, атома кислорода и атома серы, имеет бензольное кольцо или пиридиновое кольцо в качестве по меньшей мере одного из колец, образующих конденсированное кольцо, и могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы и C1-6алкильной группы").
17. Соединение или его фармацевтически приемлемая соль по п.16, где
A2 представляет собой фениленовую группу или двухвалентную группу, соответствующую следующей формуле [2]
[Химическая формула 3]
Figure 00000003
где Z1 и Z2 являются одинаковыми или отличаются и каждый из них представляет собой -CH2-, -O-, -NH-, -N(CH3)- или -S-, за исключением случая, где как Z1, так и Z2, представляют собой -CH2-.
18. Соединение или его фармацевтически приемлемая соль по п.16, где
A2 представляет собой фениленовую группу, пиридиндиильную группу, пиримидиндиильную группу, 2,4-фурандиильную группу, пиразолдиильную группу, пирролдиильную группу, "двухвалентную конденсированную кольцевую ароматическую героциклическую группу, состоящую 5-членного кольца и 6-членного кольца" или "двухвалентную конденсированную кольцевую гетероциклическую группу, имеющую частично насыщенный моноцикл, которая состоит из 5-членного кольца и 6-членного кольца" (фениленовая группа, пиридиндиильная группа, пиримидиндиильная группа, 2,4-фурандиильная группа, пиразолдиильная группа, пирролдиильная группа, "двухвалентная конденсированная кольцевая ароматическая героциклическая группа, состоящая из 5-членного кольца и 6-членного кольца" и "двухвалентная конденсированная кольцевая гетероциклическая группа, имеющая частично насыщенный моноцикл, которая состоит из 5-членного кольца и 6-членного кольца" могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, аминогруппы и C1-6алкильной группы").
19. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где
W представляет собой R6-X1-,
X1 представляет собой метиленовую группу или связь,
R6 представляет собой атом водорода, необязательно защищенную гидроксигруппу или R8-ON=CR9-,
R8 представляет собой атом водорода или С1-6алкильную группу (C1-6алкильная группа может быть замещена 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
R9 представляет собой атом водорода, C1-6алкильную группу, C3-8циклоалкильную группу, аминогруппу или C1-6алкиламиногруппу, и
группа заместителей Rc состоит из атома галогена и гидроксигруппы;
20. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где
W представляет собой R6-X2-Y1-X1-,
Y1 представляет собой -O- или -NR7-,
X1 представляет собой метиленовую группу, этиленовую группу (метиленовая группа и этиленовая группа могут быть замещены 1-2 метиловыми группами), C3-8циклоалкиленовую группу или связь,
X2 представляет собой C1-4алкиленовую группу (C1-4алкиленовая группа может быть замещена 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже),
R6 представляет собой атом водорода, атома галогена, необязательно защищенную гидроксигруппу или C1-6алкоксигруппу,
R7 представляет собой атом водорода, C1-6алкильную группу или C3-8циклоалкильную группу (C1-6алкильная группа и C3-8циклоалкильная группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из следующей группы заместителей Rc), и
группа заместителей Rc состоит из атома галогена, гидроксигруппы и C1-6алкильной группы.
21. Соединение или его фармацевтически приемлемая соль по п.1 или 2, где
W представляет собой Q-X1-Y2-X3-,
Y2 представляет собой -O-, -NR7- или связь,
X1 представляет собой C1-4алкиленовую группу (С1-4алкиленовая группа может быть замещена 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже) или связь,
X3 представляет собой метиленовую группу, этиленовую группу (метиленовая группа и этиленовая группа могут быть замещены 1-2 метильными группами), C3-8циклоалкиленовую группу или связь,
Q представляет собой C3-8циклоалкильную группу, арильную группу или гетероциклическую группу (C3-8циклоалкильная группа, арильная группа или гетероциклическая группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из группы заместителей Rc, представленной ниже);
R7 представляет собой атом водорода, С1-6алкильную группу или C3-8циклоалкильную группу (C1-6алкильная группа и С3-8циклоалкильная группа могут быть замещены 1-4 заместителями, которые являются одинаковыми или отличаются и выбраны из следующей группы заместителей Rc), и
группа заместителей Rc состоит из атома галогена, гидроксигруппы, C1-6алкильной группы, C1-6гидроксиалкильной группы, C1-6галоалкильной группы, C3-8циклоалкильной группы, C1-6алкоксигруппы (C1-6алкоксигруппа может быть замещена 1-3 гидроксигруппами или атомами галогена), C3-8циклоалкоксигруппы, C2-6алканоильной группы, C1-6алкилиденовой группы (С1-6алкилиденовая группа может быть замещена C1-6алкоксигруппой) и гидроксиаминокарбонильной группы.
22. Соединение или его фармацевтически приемлемая соль по п.1 или 2,
где W представляет собой атом водорода, атома галогена, C1-6алкильную группу, C1-6алкоксигруппу или C1-6алкиламиногруппу (C1-6алкильная группа, C1-6алкоксигруппа и C1-6алкиламиногруппа могут быть замещены 1-3 заместителями, которые являются одинаковыми или отличаются и выбраны из "атома галогена, гидроксигруппы, C1-6алкоксигруппы и морфолиногруппы").
23. Фармацевтическая композиция, содержащая соединение или его фармацевтически приемлемую соль по любому из пп.1-22.
24. Ингибитор LpxC, содержащий соединение или его фармацевтически приемлемую соль по любому из пп.1-23.
25. Противомикробное средство, содержащее соединение или его фармацевтически приемлемую соль по любому из пп.1-24.
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RU2775529C2 (ru) * 2016-12-23 2022-07-04 Интервет Интернэшнл Б.В. Соединения, применимые для лечения респираторного заболевания крупного рогатого скота или свиней
US11406617B2 (en) 2016-12-23 2022-08-09 Intervet Inc. Compounds for the treatment of bovine or swine respiratory disease

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2775529C2 (ru) * 2016-12-23 2022-07-04 Интервет Интернэшнл Б.В. Соединения, применимые для лечения респираторного заболевания крупного рогатого скота или свиней
US11406617B2 (en) 2016-12-23 2022-08-09 Intervet Inc. Compounds for the treatment of bovine or swine respiratory disease

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