RU99104179A - Diphenyl heterocycles as modulators of potassium channels - Google Patents

Diphenyl heterocycles as modulators of potassium channels

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Publication number
RU99104179A
RU99104179A RU99104179/04A RU99104179A RU99104179A RU 99104179 A RU99104179 A RU 99104179A RU 99104179/04 A RU99104179/04 A RU 99104179/04A RU 99104179 A RU99104179 A RU 99104179A RU 99104179 A RU99104179 A RU 99104179A
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Russia
Prior art keywords
phenyl
chloro
hydroxyphenyl
trifluoromethyl
methyl
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RU99104179/04A
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Russian (ru)
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RU2175319C2 (en
Inventor
Джеффри Л. РОМИН
Скотт В. Мартин
Пиасена Хевавасам
Николас А. Минвелл
Валентин К. ГРИБКОФФ
Джон Е. Джр СТЭРРЕТТ
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Бристол-Маерс Сквибб Компани
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Claims (1)

1. Соединение формулы (1)
Figure 00000001

где Het обозначает фрагмент, выбранный из группы, состоящей из (А)-(Н):
Figure 00000002

Figure 00000003

Figure 00000004

Figure 00000005

где Z независимо для каждого случая выбирают из О или S;
Ra, Rb и Rc каждый независимо выбирают из водорода, галогена, ОН, CF3 или -(-NH-CO-CH2-)p-NRfRg, при условии, что Rc не является водородом; и где Ra и Rb обозначают водород; Rc может быть гетероциклом, выбранным из группы, включающей имидазол-1-ил, морфолинометил, N-метилимидазо-2-ил и пиридин-2-ил;
Rd и Re каждый независимо выбран из водорода, галогена, CF3, NO2 или имидазол-1-ила;
m, n и p каждый независимо выбран из 0 или 1;
и Rf и Rg каждый независимо обозначает водород, C1-4 алкил; или Rf и Rg взятые вместе с атомом азота, к которому они присоединены, образуют гетероцикл, выбранный из группы, состоящей из N-метилпиперазина, морфолина, тиоморфолина, N-бензилпиперазина и имидазолинона;
или его нетоксичная фармацевтически приемлемая соль или сольват.1. The compound of formula (1)
Figure 00000001

where Het denotes a fragment selected from the group consisting of (A) - (H):
Figure 00000002

Figure 00000003

Figure 00000004

Figure 00000005

where Z is independently for each case selected from O or S;
R a , R b and R c are each independently selected from hydrogen, halogen, OH, CF 3 or - (- NH — CO — CH 2 -) p —NR f R g , provided that R c is not hydrogen; and where R a and R b denote hydrogen; R c may be a heterocycle selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazo-2-yl and pyridin-2-yl;
R d and R e are each independently selected from hydrogen, halogen, CF 3 , NO 2 or imidazol-1-yl;
m, n and p are each independently selected from 0 or 1;
and R f and R g each independently represents hydrogen, C 1-4 alkyl; or R f and R g taken together with the nitrogen atom to which they are attached form a heterocycle selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone;
or a non-toxic pharmaceutically acceptable salt or solvate thereof. 2. Соединение по п. 1, отличающееся тем, что Het представляет собой триазолоновый фрагмент группы (С) или (F) m = n = 0. 2. The compound according to claim 1, wherein Het is a triazolone moiety of the group (C) or (F) m = n = 0. 3. Соединение по п. 2, выбранное из группы, включающей:
1-(5-хлор-2-гидроксифенил)-3-[4-(трифторметил)фенил]-1,2,4
Figure 00000006
триазол-5-он;
1-(4-амино-5-хлор-2-гидроксифенил)-3-[4-(трифторметил)фенил]-1,2,4
Figure 00000007
триазол-5-он;
1-(5-хлор-2-гидроксифенил)-3-[3-(трифторметил)фенил]-1,2,4
Figure 00000008
триазол-5-он;
1-(5-хлор-2-гидроксифенил)-3-[2-(трифторметил)фенил]-1,2,4
Figure 00000009
триазол-5-он;
1-(5-хлор-2-гидроксифенил)-3-[3,5-бис(трифторметил)фенил]-1,2,4
Figure 00000010
триазол-5-он;
1-(5-хлор-2-гидроксифенил)-3-[2,4-бис(трифторметил)фенил]-1,2,4
Figure 00000011
триазол-5-он;
1-(5-хлор-2-гидроксифенил)-3-[3-хлор-4-(трифторметил)фенил]-1,2,4
Figure 00000012
триазол-5-он;
5-[5-хлор-2-гидроксифенил] -2,4-дигидро-4-[4-(трифторметил)фенил] -1,2,4
Figure 00000013
триазол-3-он;
4-(5-хлор-2-гидроксифенил)-5-[3,5-бис(трифторметил)фенил] -2,4-дигидро-(3H)-1,2,4-триазол-3-он;
4-(5-хлор-2-гидроксифенил)-5-[4-(трифторметил)фенил] -2,4-дигидро-(3H)-1,2,4-триазол-3-он;
4-(5-хлор-2-гидроксифенил)-5-[3-(трифторметил)фенил] -2,4-дигидро-(3H)-1,2,4-триазол-3-он;
4-(5-хлор-2-гидроксифенил)-5-(4-фторфенил)-2,4-дигидро-(3Н)-1,2,4-триазол-3-он; и
[2-гидрокси-5-(трифторметил)фенил] -5-[4-(трифторметил)фенил] -2,4-дигидро-4(3Н)-1,2,4-триазол-3-он.3. The compound according to claim 2, selected from the group including:
1- (5-chloro-2-hydroxyphenyl) -3- [4- (trifluoromethyl) phenyl] -1,2,4
Figure 00000006
triazole-5-one;
1- (4-amino-5-chloro-2-hydroxyphenyl) -3- [4- (trifluoromethyl) phenyl] -1,2,4
Figure 00000007
triazole-5-one;
1- (5-chloro-2-hydroxyphenyl) -3- [3- (trifluoromethyl) phenyl] -1,2,4
Figure 00000008
triazole-5-one;
1- (5-chloro-2-hydroxyphenyl) -3- [2- (trifluoromethyl) phenyl] -1,2,4
Figure 00000009
triazole-5-one;
1- (5-chloro-2-hydroxyphenyl) -3- [3,5-bis (trifluoromethyl) phenyl] -1,2,4
Figure 00000010
triazole-5-one;
1- (5-chloro-2-hydroxyphenyl) -3- [2,4-bis (trifluoromethyl) phenyl] -1,2,4
Figure 00000011
triazole-5-one;
1- (5-chloro-2-hydroxyphenyl) -3- [3-chloro-4- (trifluoromethyl) phenyl] -1,2,4
Figure 00000012
triazole-5-one;
5- [5-chloro-2-hydroxyphenyl] -2,4-dihydro-4- [4- (trifluoromethyl) phenyl] -1,2,4
Figure 00000013
triazole-3-one;
4- (5-chloro-2-hydroxyphenyl) -5- [3,5-bis (trifluoromethyl) phenyl] -2,4-dihydro- (3H) -1,2,4-triazol-3-one;
4- (5-chloro-2-hydroxyphenyl) -5- [4- (trifluoromethyl) phenyl] -2,4-dihydro- (3H) -1,2,4-triazol-3-one;
4- (5-chloro-2-hydroxyphenyl) -5- [3- (trifluoromethyl) phenyl] -2,4-dihydro (3H) -1,2,4-triazol-3-one;
4- (5-chloro-2-hydroxyphenyl) -5- (4-fluorophenyl) -2,4-dihydro (3H) -1,2,4-triazol-3-one; and
[2-hydroxy-5- (trifluoromethyl) phenyl] -5- [4- (trifluoromethyl) phenyl] -2,4-dihydro-4 (3H) -1,2,4-triazol-3-one. 4. Соединение по п. 1, отличающееся тем, что Het представляет собой триазолоновый фрагмент группы (С) или (F) и m = 1 и n = 0 или m = 0 и n = 1. 4. The compound according to claim 1, wherein Het is a triazolone moiety of the group (C) or (F) and m = 1 and n = 0 or m = 0 and n = 1. 5. Соединение по п. 4, выбранное из группы, включающей:
5-(5-хлор-2-гидроксифенил)-4-[[4-(трифторметил)фенил]метил]-2,4-дигидро-(3Н)-1,2,4-триазол-3-он;
2-[(4-амино-5-хлор-2-гидроксифенил)метил]-2,4-дигидро-5-[4-(трифторметил)фенил]-(3Н)-1,2,4-триазол-3-он;
2-[(4-амино-5-хлор-2-гидроксифенил)метил] -2,4-дигидро-5-[3,4-дихлорфенил]-(3Н)-1,2,4-триазол-3-он;
2-[(5-хлор-2-гидроксифенил)метил]-2,4-дигидро-5-[4-(трифторметил)-фенил] -(3Н)-1,2,4-триазол-3-он; и
4-(5-хлор-2-гидроксифенил)-5-[[(трифторметил)фенил] метил-2,4-дигидро-(3Н)-1,2,4-триазол-3-он.5. The compound according to claim 4, selected from the group including:
5- (5-chloro-2-hydroxyphenyl) -4 - [[4- (trifluoromethyl) phenyl] methyl] -2,4-dihydro- (3H) -1,2,4-triazol-3-one;
2 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -2,4-dihydro-5- [4- (trifluoromethyl) phenyl] - (3H) -1,2,4-triazole-3- he;
2 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -2,4-dihydro-5- [3,4-dichlorophenyl] - (3H) -1,2,4-triazol-3-one ;
2 - [(5-chloro-2-hydroxyphenyl) methyl] -2,4-dihydro-5- [4- (trifluoromethyl) phenyl] - (3H) -1,2,4-triazol-3-one; and
4- (5-chloro-2-hydroxyphenyl) -5 - [[(trifluoromethyl) phenyl] methyl-2,4-dihydro- (3H) -1,2,4-triazol-3-one. 6. Соединение по п. 1, отличающееся тем, что Het представляет собой оксадиазолоновый фрагмент группы (А) и m = n = 0. 6. The compound according to claim 1, wherein Het is an oxadiazolone moiety of the group (A) and m = n = 0. 7. Соединение по п. 6, выбранное из группы, включающей:
5-(4-амино-5-хлор-2-гидроксифенил)-3-[4-(трифторметил)фенил] -1,3,4-оксадиазол-2(3Н)-он;
5-(4-амино-5-хлор-2-гидроксифенил)-3-фенил-1,3,4-оксадиазол-2(3Н)-он;
5-(5-хлор-2-гидроксифенил)-3-[4-(трифторметил)фенил] -1,3,4-оксадиазол-2(3Н)-он;
5-(4-амино-5-хлор-2-гидроксифенил)-3-[3,4-дихлорфенил] -1,3,4-оксадиазол-2(3Н)-он;
8. Соединение по п. 1, отличающееся тем, что Het представляет собой оксадиазолоновый фрагмент группы (А); и m = 1 и n = 0.7. The compound according to claim 6, selected from the group including:
5- (4-amino-5-chloro-2-hydroxyphenyl) -3- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
5- (4-amino-5-chloro-2-hydroxyphenyl) -3-phenyl-1,3,4-oxadiazol-2 (3H) -one;
5- (5-chloro-2-hydroxyphenyl) -3- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
5- (4-amino-5-chloro-2-hydroxyphenyl) -3- [3,4-dichlorophenyl] -1,3,4-oxadiazol-2 (3H) -one;
8. The compound according to claim 1, wherein Het is an oxadiazolone moiety of the group (A); and m = 1 and n = 0. 9. Соединение по п. 8, выбранное из группы, включающей:
3-[(4-амино-5-хлор-2-гидроксифенил)метил] -5-[3,4-дихлорфенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[[4-(амино)-5-хлор-2-гидроксифенил)метил] -5-[3,5-дихлорфенил]-1,3,4-оксадиазол-2(3Н)-он:
3-[(4-амино-5-хлор-2-гидроксифенил)метил] -5-[4-(трифторметил)-фенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил] -5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил] -5-[3,5-бис(трифторметил)фенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил] -5-[4-фтор-3-(трифторметил)-фенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил] -5-[2-хлор-5-(трифторметил)-фенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[[5-хлор-2-гидроксифенил)метил] -5-[3,5-дихлорфенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил] -5-[2-фтор-4-(трифторметил)-фенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[(4-амино-3,5-дихлор-2-гидроксифенил)метил] -5-[3,4-дихлорфенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил]-5-[2-(1Н-имидазол-1-ил)-4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[(5-хлор-2-гидроксифенил)метил]-5-[4-(1Н-имидазол-1-ил)-3-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[[2-гидрокси-5-(4-морфолинилметил)фенил]метил-5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[5-хлор-4-[(этилметиламино)-2-гидроксифенил]метил-5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[[2-гидрокси-5-(2-пиридинил)фенил] метил-5-[4-(трифторметил)-фенил] -1,3,4-оксадиазол-2(3Н)-он;
3-[[5-(1-метил-1Н-имидазол-2-ил)-2-гидроксифенил)метил] -5-[2-(4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[[2-гидрокси-5-(1-метил-1H-имидазол-2-ил)фенил)метил] -5-[2-(3,5-бис(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он;
3-[[2-гидрокси-5-(1Н-имидазол-1-ил)фенил)метил]-5-[(4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он:
3-[[2-гидрокси-5-(1Н-имидазол-1-ил)фенил)метил]-5-[2-(3,5-бис(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он:
N-[2-хлор-4-[[1,5-дигидро-5-оксо-3-[4-(трифторметил)фенил] -1,2,4-оксадиазол-1-ил]метил]-5-гидроксифенил]-4-морфолинацетамид;
N-[2-хлop-4-[[2,3-дигидpo-2-oкco-5-[4-(тpифтopмeтил)фeнил] -1,3,4-оксадиазол-3-ил]метил]-5-гидроксифенил]-4-тиоморфолинацетамид;
N-[2-хлор-4-[[2,3-дигидро-2-оксо-5-[4-(трифторметил)фенил] -1,3,4-оксадиазол-3-ил]метил]-5-гидроксифенил]-4-метил-1-пиперазинацетамид;
N-[2-хлор-4-[[2,3-дигидро-2-оксо-5-[4-(трифторметил)фенил] -1,3,4-оксадиазол-3-ил]метил]-5-гидроксифенил]-4-фенил-1-пиперазинацетамид;
N-[2-хлор-4-[[2,3-дигидро-2-оксо-5-[4-(трифторметил)фенил] -1,3,4-оксадиазол-3-ил]метил]-5-гидроксифенил]-4-бензил-1-пиперазинацетамид;
N-[2-хлор-4-[[2,3-дигидро-2-оксо-5-[4-(трифторметил)фенил] -1,3,4-оксадиазол-3-ил]метил]-5-гидроксифенил1-2-(диметиламино)ацетамид;
N-[2-хлор-4-[[2,3-дигидро-2-оксо-5-[1,1'-бифенил)-1,3,4-оксадиазол-3-ил] метил]-5-гидроксифенил]-4-метил-1-пиперазинацетамид;
N-[2-хлор-4-[[2,3-дигидро-2-оксо-5-[нафт-2-ил] -1,3,4-оксадиазол-3-ил] метил]-5-гидроксифенил]-4-морфолинацетамид;
3-[[5-хлор-4-(2,3-дигидро-2-оксо-1Н-имидазол-1-ил)-2-гидроксифенил] метил]-5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он; и
3-[[5-хлор-4-(2,3-дигидро-2-тио-1Н-имидазол-1-ил)-2-гидроксифенил] -метил]-5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он.9. The compound according to claim 8, selected from the group including:
3 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -5- [3,4-dichlorophenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [[4- (amino) -5-chloro-2-hydroxyphenyl) methyl] -5- [3,5-dichlorophenyl] -1,3,4-oxadiazol-2 (3H) -one:
3 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -5- [4- (trifluoromethyl) -phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [3,5-bis (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [4-fluoro-3- (trifluoromethyl) -phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [2-chloro-5- (trifluoromethyl) -phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [[5-chloro-2-hydroxyphenyl) methyl] -5- [3,5-dichlorophenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [2-fluoro-4- (trifluoromethyl) -phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(4-amino-3,5-dichloro-2-hydroxyphenyl) methyl] -5- [3,4-dichlorophenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [2- (1H-imidazol-1-yl) -4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -he;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [4- (1H-imidazol-1-yl) -3- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -he;
3 - [[2-hydroxy-5- (4-morpholinylmethyl) phenyl] methyl-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3- [5-chloro-4 - [(ethylmethylamino) -2-hydroxyphenyl] methyl-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [[2-hydroxy-5- (2-pyridinyl) phenyl] methyl-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one;
3 - [[5- (1-methyl-1H-imidazol-2-yl) -2-hydroxyphenyl) methyl] -5- [2- (4- (trifluoromethyl) phenyl] -1,3,4-oxadiazole-2 (3H) -one;
3 - [[2-hydroxy-5- (1-methyl-1H-imidazol-2-yl) phenyl) methyl] -5- [2- (3,5-bis (trifluoromethyl) phenyl] -1,3,4 -oxadiazol-2 (3H) -one;
3 - [[2-hydroxy-5- (1H-imidazol-1-yl) phenyl) methyl] -5 - [(4- (trifluoromethyl) phenyl] -1,3,4-oxadiazole-2 (3H) -one :
3 - [[2-hydroxy-5- (1H-imidazol-1-yl) phenyl) methyl] -5- [2- (3,5-bis (trifluoromethyl) phenyl] -1,3,4-oxadiazole-2 (3H) -one:
N- [2-chloro-4 - [[1,5-dihydro-5-oxo-3- [4- (trifluoromethyl) phenyl] -1,2,4-oxadiazol-1-yl] methyl] -5-hydroxyphenyl ] -4-morpholine acetamide;
N- [2-chlorop-4 - [[2,3-dihydro-2-oco-5- [4- (triptoremphenyl) phenyl] -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl ] -4-thiomorpholine acetamide;
N- [2-chloro-4 - [[2,3-dihydro-2-oxo-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl ] -4-methyl-1-piperazine acetamide;
N- [2-chloro-4 - [[2,3-dihydro-2-oxo-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl ] -4-phenyl-1-piperazine acetamide;
N- [2-chloro-4 - [[2,3-dihydro-2-oxo-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl ] -4-benzyl-1-piperazine acetamide;
N- [2-chloro-4 - [[2,3-dihydro-2-oxo-5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl1 -2- (dimethylamino) acetamide;
N- [2-chloro-4 - [[2,3-dihydro-2-oxo-5- [1,1'-biphenyl) -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl ] -4-methyl-1-piperazine acetamide;
N- [2-chloro-4 - [[2,3-dihydro-2-oxo-5- [naphth-2-yl] -1,3,4-oxadiazol-3-yl] methyl] -5-hydroxyphenyl] -4-morpholine acetamide;
3 - [[5-chloro-4- (2,3-dihydro-2-oxo-1H-imidazol-1-yl) -2-hydroxyphenyl] methyl] -5- [4- (trifluoromethyl) phenyl] -1, 3,4-oxadiazol-2 (3H) -one; and
3 - [[5-chloro-4- (2,3-dihydro-2-thio-1H-imidazol-1-yl) -2-hydroxyphenyl] -methyl] -5- [4- (trifluoromethyl) phenyl] -1 , 3,4-oxadiazol-2 (3H) -one. 10. Соединение по п. 1, отличающееся тем, что Het представляет собой имидазолоновый фрагмент группы (D) или (Е) и m = n = 0. 10. The compound according to claim 1, wherein Het is an imidazolone moiety of the group (D) or (E) and m = n = 0. 11. Соединение по п. 10, выбранное из группы, включающей:
4-хлор-2-[2-[4-(трифторметил)фенил]-1Н-имидазол-1-ил]фенол;
4-хлор-2-[1-[4-(трифторметил)фенил]-1Н-имидазол-2-ил]фенол:
4-хлор-2-[1-фенил-1Н-имидазол-2-ил] фенол; и 1-(5-хлор-2-гидроксифенил)-5-[4-(трифторметил)фенил]-1Н-имидазол.11. The compound according to claim 10, selected from the group including:
4-chloro-2- [2- [4- (trifluoromethyl) phenyl] -1H-imidazol-1-yl] phenol;
4-chloro-2- [1- [4- (trifluoromethyl) phenyl] -1H-imidazol-2-yl] phenol:
4-chloro-2- [1-phenyl-1H-imidazol-2-yl] phenol; and 1- (5-chloro-2-hydroxyphenyl) -5- [4- (trifluoromethyl) phenyl] -1H-imidazole. 12. Соединение по п. 1, выбранное из группы, включающей:
4-хлор-2-[3-амино-[5-[4-(трифторметил)фенил] -1,2,4-триазол-4(4Н)ил] ] фенол;
1-(5-хлор-2-гидроксифенил)-1,3-дигидро-5-фенил-2Н-имидазол-2-он;
3-[(5-хлор-2-гидроксифенил)метил]-5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-тион; и
4-(5-хлор-2-гидроксифенил)-5-[4-(трифторметил)фенил] -2,4-дигидро-(3Н)-1,2,4-триазол-3-тион.12. The compound according to claim 1, selected from the group including:
4-chloro-2- [3-amino- [5- [4- (trifluoromethyl) phenyl] -1,2,4-triazol-4 (4H) yl]] phenol;
1- (5-chloro-2-hydroxyphenyl) -1,3-dihydro-5-phenyl-2H-imidazol-2-one;
3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -thione; and
4- (5-chloro-2-hydroxyphenyl) -5- [4- (trifluoromethyl) phenyl] -2,4-dihydro- (3H) -1,2,4-triazole-3-thione. 13. Соединение по п. 1, представляющее собой 3-[(5-хлор-2-гидроксифенил)метил]-5-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он. 13. The compound according to claim 1, which is 3 - [(5-chloro-2-hydroxyphenyl) methyl] -5- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 (3H) -one . 14. Соединение по п. 1, представляющее собой 1-(5-хлор-2-гидроксифенил)-3-[4-(трифторметил)фенил]-1,2,4(4Н)-триазол-5-он. 14. The compound according to claim 1, which is 1- (5-chloro-2-hydroxyphenyl) -3- [4- (trifluoromethyl) phenyl] -1,2,4 (4H) -triazol-5-one. 15. Соединение по п. 1, представляющее собой 3-[(4-амино-5-хлор-2-гидроксифенил)метил]-5-[3,5-дихлорфенил]-1,3,4-оксадиазол-2(3Н)-он. 15. The compound according to claim 1, which is 3 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -5- [3,5-dichlorophenyl] -1,3,4-oxadiazol-2 (3H )-he. 16. Соединение по п. 1, представляющее собой 3-[(4-амино-5-хлор-2-гидроксифенил)метил]-5-[3,4-дихлорфенил]-1,3,4-оксадиазол-2(3Н)-он. 16. The compound according to claim 1, which is 3 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -5- [3,4-dichlorophenyl] -1,3,4-oxadiazol-2 (3H )-he. 17. Соединение по п. 1, представляющее собой 5-[(4-амино-5-хлор-2-гидроксифенил)метил]-3-[4-(трифторметил)фенил]-1,3,4-оксадиазол-2(3Н)-он. 17. The compound according to claim 1, which is 5 - [(4-amino-5-chloro-2-hydroxyphenyl) methyl] -3- [4- (trifluoromethyl) phenyl] -1,3,4-oxadiazol-2 ( 3H) -one. 18. Фармацевтическая композиция для лечения нарушений, чувствительных к веществам, открывающим активированные кальцием калиевые каналы с большой проводимостью, содержащая терапевтически эффективное количество соединения по п. 1 в сочетании с фармацевтически приемлемым носителем или разбавителем. 18. Pharmaceutical composition for treating disorders sensitive to substances that open calcium-activated potassium channels with high conductivity, containing a therapeutically effective amount of a compound according to claim 1 in combination with a pharmaceutically acceptable carrier or diluent. 19. Способ лечения нарушений, чувствительных к открыванию активированных кальцием калиевых каналов с большой проводимостью, у млекопитающего, нуждающегося в таком лечении, заключающийся во введении указанному млекопитающему терапевтически эффективного количества соединения по п. 1. 19. A method of treating disorders sensitive to the opening of calcium-activated potassium channels with high conductivity in a mammal in need of such treatment, which consists in administering to a specified mammal a therapeutically effective amount of a compound according to claim 1. 20. Способ по п. 19, отличающийся тем, что указанное нарушение представляет собой ишемию, судороги, астму, синдром раздраженной толстой кишки, мигрень, черепно-мозговую травму, нарушение эрекции у мужчин и недержание мочи. 20. The method according to p. 19, characterized in that the violation is ischemia, convulsions, asthma, irritable bowel syndrome, migraine, head injury, erection disorder in men and urinary incontinence. 21. Способ по п. 20, отличающийся тем, что указанное нарушение представляет собой церебральную ишемию. 21. The method according to p. 20, characterized in that the violation is cerebral ischemia.
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