RU2013132524A - Ингибиторы неприлизина - Google Patents

Ингибиторы неприлизина Download PDF

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RU2013132524A
RU2013132524A RU2013132524/04A RU2013132524A RU2013132524A RU 2013132524 A RU2013132524 A RU 2013132524A RU 2013132524/04 A RU2013132524/04 A RU 2013132524/04A RU 2013132524 A RU2013132524 A RU 2013132524A RU 2013132524 A RU2013132524 A RU 2013132524A
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Russia
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alkylene
alkyl
halogen
och
phenyl
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RU2013132524/04A
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RU2605557C2 (ru
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Камерон СМИТ
Мелисса Флери
Роланд Гендрон
Райан ХАДСОН
Адам Д. ХЬЮЗ
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Тереванс, Инк.
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
    • C07C281/02—Compounds containing any of the groups, e.g. carbazates
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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Abstract

1. Соединение формулы I:,где Rвыбран из -ORи -NRR;Rпредставляет собой H или -P(O)(OH), или Rберут вместе с R, получая -CRR-, или берут вместе с R, получая -C(O)-;X представляет собой -Cгетероарил;Rотсутствует или выбран из H; галогена; -Cалкилен-OH; -NH; -Cалкила; -CF; -Cциклоалкила; -Cалкилен-O-Cалкила; -C(O)R; -Cалкилен-COOR; -C(O)NRR; -NHC(O)R; =O; -NO; -C(CH)=N(OH); фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -OH, -CF, -OCH, -NHC(O)CHи фенила; нафталенила; пиридинила; пиразинила; пиразолила, необязательно замещенного метилом; тиофенила, необязательно замещенного метилом или галогеном; фуранила; и -CH-морфолинила; и R, когда он присутствует, соединен с атомом углерода;Rотсутствует или выбран из H; -OH; -Cалкила; -Cалкилен-COOR; -CHOC(O)CH(R)NH; -OCHOC(O)CH(R)NH; -OCHOC(O)CH; -CHOP(O)(OH); -CHCH(OH)CHOH; -CH[CH(CH)]-NHC(O)O-Cалкила; пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена, -COOR, -OCH, -OCFи -SCF; и R, когда он присутствует, соединен с атомом углерода или атомом азота;или Rи Rберут вместе, получая -фенилен-O-(CH)- или -фенилен-O-CH-CHOH-CH-;a равен 0 или 1; Rвыбран из галогена, -CH, -CFи -CN;b равен 0 или целому от 1 до 3; каждый Rнезависимо выбран из галогена, -OH, -CH, -OCHи -CF;Rвыбран из H, -Cалкила, -Cалкилен-Cарила, -Cалкилен-Cгетероарила, -Cциклоалкила, -[(CH)O]CH, -Cалкилен-OC(O)R, -Cалкилен-NRR, -Cалкилен-C(O)R, -Cалкиленморфолинила; -Cалкилен-SO-Cалкила;Rвыбран из -Cалкила, -O-Cалкила, -Cциклоалкила, -O-Cциклоалкила, фенила, -O-фенила, -NRR, -CH[CH(CH)]-NH, -CH[CH(CH)]-NHC(O)O-Cалкила и -CH(NH)CHCOOCH; и Rи Rнезависимо выбраны из H, -Cалкила и бензила; или Rи Rберут вместе как -(CH)-, -C(O)-(CH)- или -(CH)O(CH)-; и Rвыбран из -O-Cалкила, -O-бензила и -NRR; Rпредставляет собой -Cалкил или -Cалкилен-Cарил;Rвыбран из H, -OH, -OC(O)R, -CHCOOH, -O-бензила, пириди�

Claims (27)

1. Соединение формулы I:
Figure 00000001
,
где R1 выбран из -OR7 и -NR8R9;
R2 представляет собой H или -P(O)(OH)2, или R2 берут вместе с R7, получая -CR18R19-, или берут вместе с R8, получая -C(O)-;
X представляет собой -C1-9гетероарил;
R3 отсутствует или выбран из H; галогена; -C0-5алкилен-OH; -NH2; -C1-6алкила; -CF3; -C3-7циклоалкила; -C0-2алкилен-O-C1-6алкила; -C(O)R20; -C0-1алкилен-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3)=N(OH); фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -OH, -CF3, -OCH3, -NHC(O)CH3 и фенила; нафталенила; пиридинила; пиразинила; пиразолила, необязательно замещенного метилом; тиофенила, необязательно замещенного метилом или галогеном; фуранила; и -CH2-морфолинила; и R3, когда он присутствует, соединен с атомом углерода;
R4 отсутствует или выбран из H; -OH; -C1-6алкила; -C1-2алкилен-COOR35; -CH2OC(O)CH(R36)NH2; -OCH2OC(O)CH(R36)NH2; -OCH2OC(O)CH3; -CH2OP(O)(OH)2; -CH2CH(OH)CH2OH; -CH[CH(CH3)2]-NHC(O)O-C1-6алкила; пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена, -COOR35, -OCH3, -OCF3 и -SCF3; и R4, когда он присутствует, соединен с атомом углерода или атомом азота;
или R3 и R4 берут вместе, получая -фенилен-O-(CH2)1-3- или -фенилен-O-CH2-CHOH-CH2-;
a равен 0 или 1; R5 выбран из галогена, -CH3, -CF3 и -CN;
b равен 0 или целому от 1 до 3; каждый R6 независимо выбран из галогена, -OH, -CH3, -OCH3 и -CF3;
R7 выбран из H, -C1-8алкила, -C1-3алкилен-C6-10арила, -C1-3алкилен-C1-9гетероарила, -C3-7циклоалкила, -[(CH2)2O]1-3CH3, -C1-6алкилен-OC(O)R10, -C1-6алкилен-NR12R13, -C1-6алкилен-C(O)R31, -C0-6алкиленморфолинила; -C1-6алкилен-SO2-C1-6алкила;
Figure 00000002
R10 выбран из -C1-6алкила, -O-C1-6алкила, -C3-7циклоалкила, -O-C3-7циклоалкила, фенила, -O-фенила, -NR12R13, -CH[CH(CH3)2]-NH2, -CH[CH(CH3)2]-NHC(O)O-C1-6алкила и -CH(NH2)CH2COOCH3; и R12 и R13 независимо выбраны из H, -C1-6алкила и бензила; или R12 и R13 берут вместе как -(CH2)3-6-, -C(O)-(CH2)3- или -(CH2)2O(CH2)2-; и R31 выбран из -O-C1-6алкила, -O-бензила и -NR12R13; R32 представляет собой -C1-6алкил или -C0-6алкилен-C6-10арил;
R8 выбран из H, -OH, -OC(O)R14, -CH2COOH, -O-бензила, пиридила и -OC(S)NR15R16; R14 выбран из H, -C1-6алкила, -C6-10арила, -OCH2-С6-10арила, -CH2O-C6-10арила и -NR15R16; и R15 и R16 независимо выбраны из H и -C1-4алкила;
R9 выбран из H, -C1-6алкила и -C(O)R17; и R17 выбран из H, -C1-6алкила, -C3-7циклоалкила, -C6-10арила и -C1-9гетероарила;
R18 и R19 независимо выбраны из H, -C1-6алкила и -O-C3-7циклоалкила, или R18 и R19 берут вместе, получая =O;
R20 выбран из H и -C1-6алкила;
R21 и R35 независимо выбраны из H, -C1-6алкила, -C1-3алкилен-C6-10арила, -C1-3алкилен-C1-9гетероарила, -C3-7циклоалкила, -[(CH2)2O]1-3CH3, -C1-6алкилен-OC(O)R25; -C1-6алкилен-NR27R28, -C1-6алкилен-C(O)R33, -C0-6алкиленморфолинила, -C1-6алкилен-SO2-C1-6алкила,
Figure 00000003
R25 выбран из -C1-6алкила, -O-C1-6алкила, -C3-7циклоалкила, -O-C3-7циклоалкила, фенила, -O-фенила, -NR27R28, -CH[CH(CH3)2]-NH2, -CH[CH(CH3)2]-NHC(O)O-C1-6алкила и -CH(NH2)CH2COOCH3; R27 и R28 независимо выбраны из H, -C1-6алкила и бензила; или R27 и R28 берут вместе в виде -(CH2)3-6-, -C(O)-(CH2)3- или -(CH2)2O(CH2)2-; R33 выбран из -O-C1-6алкила, -O-бензила и -NR27R28; и R34 представляет собой -C1-6алкил или -C0-6алкилен-C6-10арил;
R22 и R23 независимо выбраны из H, -C1-6алкила, -CH2COOH, -(CH2)2OH; -(CH2)2OCH3, -(CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1алкилен-C3-7циклоалкила и -(CH2)2-имидазолила; или R22 и R23 берут вместе, получая насыщенный или частично ненасыщенный -C3-5гетероцикл, необязательно замещенный галогеном, -OH, -COOH или -CONH2; и необязательно содержащий атом кислорода в кольце;
R24 выбран из -C1-6алкила; -C0-1алкилен-O-C1-6алкила; фенила, необязательно замещенного галогеном или -OCH3; и -C1-9гетероарила; и
R36 выбран из H, -CH(CH3)2, фенила и бензила;
где каждая алкильная группа в R1, R3 и R4 необязательно замещена 1-8 атомами фтора; и
где метиленовый линкер в бифениле необязательно замещен одной или двумя -C1-6алкильными группами или циклопропилом;
или его фармацевтически приемлемая соль.
2. Соединение по п. 1, где X выбран из пиразола, имидазола, триазола, бензотриазола, фурана, пиррола, тетразола, пиразина, тиофена, оксазола, изоксазола, тиазола, изотиазола, оксадиазола, тиадиазола, пиридазина, пиридина, пиримидина, пирана, бензимидазола, бензоксазола, бензотиазола, пиридилимидазола и пиридилтриазола.
3. Соединение по п. 2, где X выбран из пиразола, триазола, бензотриазола, тетразола, оксазола, изоксазола, тиазола, пиридазина, пиримидина и пиридилтриазола.
4. Соединение по п. 1, где R1 выбран из -OR7 и -NR8R9, где R7 представляет собой H, R8 представляет собой H или -OH, и R9 представляет собой H.
5. Соединение по п. 1, где:
R1 представляет собой -OR7; и R7 выбран из -C1-8алкила, -C1-3алкилен-C6-10арила, -C1-3алкилен-C1-9гетероарила, -C3-7циклоалкила, -[(CH2)2O]1-3CH3, -C1-6алкилен-OC(O)R10, -C1-6алкилен-NR12R13, -C1-6алкилен-C(O)R31, -C0-6алкиленморфолинила, -C1-6алкилен-SO2-C1-6алкила,
Figure 00000004
R1 представляет собой -NR8R9; R8 выбран из -OC(O)R14, -CH2COOH, -O-бензила, пиридила и -OC(S)NR15R16; и R9 представляет собой H; или
R1 представляет собой -NR8R9; R8 выбран из -OC(O)R14, -CH2COOH, -O-бензила, пиридила и -OC(S)NR15R16; и R9 представляет собой -C1-6алкил или -C(O)R17;
R1 представляет собой -NR8R9; R8 выбран из H или -OH; и R9 выбран из -C1-6алкила и -C(O)R17;
R1 представляет собой -OR7, и R2 берут вместе с R7, получая -CR18R19-; или
R1 представляет собой -NR8R9, и R2 берут вместе с R8, получая -C(O)-.
6. Соединение по п. 1, где R1 представляет собой -OR7, где R7 выбран из H, -C1-8алкила, -C1-3алкилен-C6-10арила, -C0-6алкиленморфолинила и
Figure 00000005
где R32 представляет собой -C1-6алкил; и где каждая алкильная группа необязательно замещена 1-8 атомами фтора.
7. Соединение по п. 1, где R2 представляет собой H.
8. Соединение по п. 1, где R3 отсутствует или выбран из H; галогена; -C0-5алкилен-OH; -NH2; -C1-6алкила; -CF3; -C3-7циклоалкила; -C0-2алкилен-O-C1-6алкила; -C(O)R20; -C0-1алкилен-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3)=N(OH); фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -OH, -CF3, -OCH3, -NHC(O)CH3 и фенила; нафталенила; пиридинила; пиразинила; пиразолила, необязательно замещенного метилом; тиофенила, необязательно замещенного метилом или галогеном; фуранила; и -CH2-морфолинила; и R21 представляет собой H.
9. Соединение по п. 1, где R3 представляет собой -C0-1алкилен-COOR21; и R21 выбран из -C1-6алкила, -C1-3алкилен-C6-10арила, -C1-3алкилен-C1-9гетероарила, -C3-7циклоалкила, -[(CH2)2O]1-3CH3, -C1-6алкилен-OC(O)R25; -C1-6алкилен-NR27R28, -C1-6алкилен-C(O)R33, -C0-6алкиленморфолинила, -C1-6алкилен-SO2-C1-6алкила,
Figure 00000006
10. Соединение по п. 1, где R3 отсутствует или выбран из H; галогена; -C0-5алкилен-OH; -C1-6алкила; -C3-7циклоалкила; -C0-2алкилен-O-C1-6алкила; -C(O)R20; -C0-1алкилен-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -OH и -OCH3; пиридинила; и пиразинила; R20 представляет собой -C1-6алкил; R21 представляет собой H; R22 представляет собой H или -C1-6алкил; R23 выбран из -C1-6алкила, -(CH2)2OH, -(CH2)2OCH3, -(CH2)2SO2NH2 и -C0-1алкилен-C3-7циклоалкила; или R22 и R23 берут вместе, получая насыщенный или частично ненасыщенный -C3-5гетероцикл, необязательно замещенный галогеном или -OH, и необязательно содержащий атом кислорода в кольце; и R24 представляет собой фенил, замещенный -OCH3.
11. Соединение по п. 1, где R4 отсутствует или выбран из H; -OH; -C1-6алкила; -C1-2алкилен-COOR35; -CH2OC(O)CH(R36)NH2, -CH2CH(OH)CH2OH; пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена, -COOR35, -OCH3, -OCF3 и -SCF3; и R35 представляет собой H.
12. Соединение по п. 1, где R4 выбран из -OCH2OC(O)CH3; -CH2OP(O)(OH)2; -C1-2алкилен-COOR35; и фенила или бензила, замещенного по меньшей мере одной -COOR35 группой; где R35 выбран из -C1-6алкила, -C1-3алкилен-C6-10арила, -C1-3алкилен-C1-9гетероарила, -C3-7циклоалкила, -[(CH2)2O]1-3CH3, -C1-6алкилен-OC(O)R25; -C1-6алкилен-NR27R28, -C1-6алкилен-C(O)R33, -C0-6алкиленморфолинила, -C1-6алкилен-SO2-C1-6алкила,
Figure 00000007
13. Соединение по п. 1, где R4 выбран из H; -OH; -C1-2алкилен-COOR35; пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена и -OCH3; и R35 представляет собой H.
14. Соединение по п. 1, где a равно 0; или a равно 1, и R5 выбран из галогена и -CN.
15. Соединение по п. 1, где b равно 0; или b равно 1, и R6 выбран из Cl, F, -OH, -CH3, -OCH3 и -CF3; или b равно 2, и каждый R6 независимо представляет собой галоген, -OH, -CH3 или -OCH3; или b равно 3, и каждый R6 независимо представляет собой галоген или -CH3.
16. Соединение по п. 1, где R1 представляет собой OR7; R2 представляет собой H; X выбран из пиразола, триазола, бензотриазола, тетразола, оксазола, изоксазола, тиазола, пиридазина, пиримидина и пиридилтриазола; R3 отсутствует или выбран из H; галогена; -C0-5алкилен-OH; -C1-6алкила; -C3-7циклоалкила; -C0-2алкилен-O-C1-6алкила; -C(O)R20; -C0-1алкилен-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; фенила, необязательно замещенного одной или двумя группами, независимо выбранными из галогена, -OH и -OCH3; пиридинила; и пиразинила; R4 выбран из H; -OH; -C1-2алкилен-COOR35; пиридинила; и фенила или бензила, необязательно замещенного одной или более группами, выбранными из галогена и -OCH3; a равно 0; или a равно 1, и R5 выбран из галогена и -CN; b равно 0; или b равно 1, и R6 выбран из Cl, F, -OH, -CH3, -OCH3 и -CF3; или b равно 2, и каждый R6 независимо представляет собой галоген, -OH, -CH3 или -OCH3; или b равно 3, и каждый R6 независимо представляет собой галоген или -CH3; R7 выбран из H, -C1-8алкила, -C1-3алкилен-C6-10арила, -C0-6алкиленморфолинила и
Figure 00000008
R32 представляет собой -C1-6алкил; R20 представляет собой -C1-6алкил; R21 представляет собой H; R22 представляет собой H или -C1-6алкил; R23 выбран из -C1-6алкила, -(CH2)2OH, -(CH2)2OCH3, -(CH2)2SO2NH2 и -C0-1алкилен-C3-7циклоалкила; или R22 и R23 берут вместе, получая насыщенный или частично ненасыщенный -C3-5гетероцикл, необязательно замещенный галогеном или -OH, и необязательно содержащий атом кислорода в кольце; R24 представляет собой фенил, замещенный -OCH3; и R35 представляет собой H; и где каждая алкильная группа в R1 необязательно замещена 1-8 атомами фтора.
17. Соединение по п. 1, где R1 представляет собой OR7; R2 представляет собой H; X выбран из пиразола, триазола, бензотриазола, тетразола, оксазола, изоксазола, тиазола, пиридазина и пиримидина; R3 отсутствует или выбран из H; галогена; -C0-5алкилен-OH; -C1-6алкила; -C3-7циклоалкила; -C0-2алкилен-O-C1-6алкила; -C(O)R20; -C0-1алкилен-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; фенила, замещенного одной или двумя группами, независимо выбранными из галогена, -OH и -OCH3; пиридинила; и пиразинила; R4 выбран из H, -OH и фенила, необязательно замещенного галогеновой группой; a равно 0; или a равно 1, и R5 представляет собой галоген; b равно 0; или b равно 1, и R6 представляет собой галоген или -CH3; или b равно 2, и каждый R6 независимо представляет собой галоген, -OH, -CH3 или -OCH3; R20 представляет собой -C1-6алкил; R21 представляет собой H; R22 представляет собой -C1-6алкил; R23 представляет собой -C1-6алкил или -C0-1алкилен-C3-7циклоалкил; или R22 и R23 берут вместе, получая насыщенный -C3-5гетероцикл, необязательно замещенный галогеном или -OH; и R24 представляет собой фенил, замещенный -OCH3.
18. Способ получения соединения по любому из пунктов 1-17, включающий стадию конденсации соединения формулы 1 с соединением формулы 2:
Figure 00000009
получая соединение формулы I; где P1 представляет собой H или амино-защитную группу, выбранную из трет-бутоксикарбонила, тритила, бензилоксикарбонила, 9-флуоренилметоксикарбонила, формила, триметилсилила и трет-бутилдиметилсилила; и где способ дополнительно включает снятие защитной группы соединения формулы 1, когда P1 представляет собой амино-защитную группу.
19. Промежуточное соединение, пригодное для получения соединений по любому из пп. 1-17, имеющее формулу 1
Figure 00000010
где P1 представляет собой H или амино-защитную группу, выбранную из трет-бутоксикарбонила, тритила, бензилоксикарбонила, 9-флуоренилметоксикарбонила, формила, триметилсилила и трет-бутилдиметилсилила; или его соль.
20. Способ получения соединения по любому из пп. 1-17, включающий стадию снятие защитной группы соединения, выбранного из:
Figure 00000011
или его соли; где R1P выбран из -O-P3, -NHP2 и -NH(O-P4); R3P выбран из -C0-5алкилен-O-P4, -C0-1алкилен-COO-P3 и фенила, замещенного -O-P4; R4P выбран из -O-P4; -C1-2алкилен-COO-P3; и фенила или бензила, замещенного -COO-P3; P2 представляет собой амино-защитную группу, выбранную из трет-бутоксикарбонила, тритила, бензилоксикарбонила, 9-флуоренилметоксикарбонила, формила, триметилсилила и трет-бутилдиметилсилила; P3 представляет собой карбокси-защитную группу, выбранную из метила, этила, трет-бутила, бензила, п-метоксибензила, 9-флуоренилметила, триметилсилила, трет-бутилдиметилсилила и дифенилметила; и P4 представляет собой гидроксил-защитную группу, выбранную из -C1-6алкила, триС1-6алкилсилила, -C1-6алканоила, бензоила, бензила, п-метоксибензила, 9-флуоренилметила и дифенилметила.
21. Промежуточное соединение, пригодное для получения соединений по любому из пп. 1-17, выбранное из:
Figure 00000012
или его соль; где R1P выбран из -O-P3, -NHP2 и -NH(O-P4); R3P выбран из -C0-5алкилен-O-P4, -C0-1алкилен-COO-P3 и фенила, замещенного -O-P4; R4P выбран из -O-P4; -C1-2алкилен-COO-P3; и фенила или бензила, замещенного -COO-P3; P2 представляет собой амино-защитную группу, выбранную из трет-бутоксикарбонила, тритила, бензилоксикарбонила, 9-флуоренилметоксикарбонила, формила, триметилсилила и трет-бутилдиметилсилила; P3 представляет собой карбокси-защитную группу, выбранную из метила, этила, трет-бутила, бензила, п-метоксибензила, 9-флуоренилметила, триметилсилила, трет-бутилдиметилсилила и дифенилметила; и P4 представляет собой гидроксил-защитную группу, выбранную из -C1-6алкила, триС1-6алкилсилила, -C1-6алканоила, бензоила, бензила, п-метоксибензила, 9-флуоренилметила и дифенилметила.
22. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-17 и фармацевтически приемлемый носитель.
23. Фармацевтическая композиция по п. 22, дополнительно содержащая терапевтический агент, выбранный из антагонистов аденозинового рецептора, антагонистов α-адренергического рецептора, антагонистов β1-адренергического рецептора, агонистов β2-адренергического рецептора, антагониста β-адренергического рецептора/антагониста α1-рецептора двойного действия, агентов, разрушающих конечный продукт усиленного гликозилирования, антагонистов альдостерона, ингибиторов альдостеронсинтазы, ингибиторов аминопептидазы N, андрогенов, ингибиторов ангиотензин-превращающего фермента и ингибиторов ангиотензин-превращающего фермента/неприлизина двойного действия, активаторов и стимуляторов ангиотензин-превращающего фермента 2, ангиотензин-II вакцин, антикоагулянтов, противодиабетических агентов, противодиарейных агентов, агентов против глаукомы, антилипидных агентов, антиноцицептивных агентов, противотромботических агентов, антагонистов AT1 рецептора и антагониста AT1 рецептора/ингибитора неприлизина двойного действия и блокаторов многофункционального ангиотензинового рецептора, антагонистов рецептора брадикинина, блокаторов кальциевых каналов, ингибиторов химазы, дигоксина, диуретиков, агонистов допамина, ингибиторов эндотелин-превращающего фермента, антагонистов эндотелинового рецептора, ингибиторов HMG-CoA редуктазы, эстрогенов, агонистов и/или антагонистов эстрогенового рецептора, ингибиторов обратного захвата моноаминов, мышечных релаксантов, натрийуретических пептидов и их аналогов, антагонистов очищающего рецептора натрийуретического пептида, ингибиторов неприлизина, доноров оксида азота, нестероидных противовоспалительных агентов, антагонистов рецептора N-метил d-аспартата, агонистов опиоидных рецепторов, ингибиторов фосфодиэстеразы, простагландиновых аналогов, агонистов простагландинового рецептора, ингибиторов ренина, селективных ингибиторов обратного захвата серотонина, блокатора натриевых каналов, стимуляторов и активаторов растворимой гуанилатциклазы, трициклических антидепрессантов, антагонистов вазопрессинового рецептора и их комбинаций.
24. Фармацевтическая композиция по п. 23, где терапевтический агент представляет собой антагонист AT1 рецептора.
25. Соединение по любому из пп. 1-17 для применения в терапии.
26. Соединение по п. 25 для применения в лечении гипертензии, сердечной недостаточности или заболевания почек.
27. Применение соединения по любому из пп. 1-17 для получения лекарственного средства для лечения гипертензии, сердечной недостаточности или заболевания почек.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2726623C2 (ru) * 2015-02-11 2020-07-15 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи (2s,4r)-5-(5'-хлор-2'-фторбифенил-4-ил)-4-(этоксиоксалиламино)-2-гидроксиметил-2-метилпентановая кислота

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100518998C (zh) * 2005-09-29 2009-07-29 宝山钢铁股份有限公司 薄带连铸结晶辊加热方法和装置
ES2548887T3 (es) 2010-12-15 2015-10-21 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
ES2550324T3 (es) 2010-12-15 2015-11-06 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
EP2675792B1 (en) * 2011-02-17 2016-01-06 Theravance Biopharma R&D IP, LLC Substituted aminobutyric derivatives as neprilysin inhibitors
RU2604522C2 (ru) * 2011-02-17 2016-12-10 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи,ЭлЭлСи Замещенные аминомасляные производные в качестве ингибиторов неприлизина
EP2714662B1 (en) 2011-05-31 2017-10-11 Theravance Biopharma R&D IP, LLC Neprilysin inhibitors
EP2714660B1 (en) 2011-05-31 2018-09-26 Theravance Biopharma R&D IP, LLC Neprilysin inhibitors
TWI560172B (en) 2011-11-02 2016-12-01 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
US9271965B2 (en) 2012-03-28 2016-03-01 Theravance Biopharma R&D Ip, Llc Crystalline forms of (R)-3-[N-(3'-chlorobiphenyl-4-ylmethyl)-N'-(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxyproprionic acid isopropyl ester
JP6088047B2 (ja) * 2012-05-31 2017-03-01 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー 一酸化窒素ドナーであるネプリライシン阻害剤
CA2873328A1 (en) 2012-06-08 2013-12-12 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
US9108934B2 (en) 2012-06-08 2015-08-18 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
NZ704741A (en) 2012-08-08 2017-10-27 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
EP2964616B1 (en) 2013-03-05 2017-05-03 Theravance Biopharma R&D IP, LLC Neprilysin inhibitors
JP2017507921A (ja) 2014-01-30 2017-03-23 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ネプリライシン阻害剤
JP2017504625A (ja) 2014-01-30 2017-02-09 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ネプリライシン阻害剤としての５−ビフェニル−４−ヘテロアリールカルボニルアミノ−ペンタン酸誘導体
RU2715241C2 (ru) 2015-02-19 2020-02-26 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи (2r,4r)-5-(5′-хлор-2′-фторбифенил-4-ил)-2-гидрокси-4-[(5-метилоксазол-2-карбонил)амино]пентановая кислота
WO2017156009A1 (en) 2016-03-08 2017-09-14 Theravance Biopharma R&D Ip, Llc Crystalline(2s,4r)-5-(5'-chloro-2'-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid and uses thereof
EP3548039B1 (en) 2016-12-04 2023-07-19 Alavi Khorassani Moghadam, Marcel Victor Ribavirin for use in the treatment of a mitochondrial disease
TWI794385B (zh) 2018-01-03 2023-03-01 美商藝康美國公司 作為腐蝕抑制劑之苯并三唑衍生物
UY38072A (es) 2018-02-07 2019-10-01 Novartis Ag Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189604A (en) 1975-07-22 1980-02-19 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Bestatin
US4206232A (en) 1976-05-10 1980-06-03 E. R. Squibb & Sons, Inc. Relieving hypertension with carboxyalkylacylamino acids
IL58849A (en) 1978-12-11 1983-03-31 Merck & Co Inc Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
FR2480747A1 (fr) 1980-04-17 1981-10-23 Roques Bernard Derives d'acides amines et leur application therapeutique
US4906615A (en) 1980-12-18 1990-03-06 Schering Corporation Substituted dipeptides as inhibitors of enkephalinases
US4722810A (en) 1984-08-16 1988-02-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
US4939261A (en) 1984-06-08 1990-07-03 Ciba-Geigy Corporation N-substituted butyramide derivatives useful for treatment of conditions responsive to inhibition of enkephalinase
EP0225292A3 (en) 1985-12-06 1988-11-30 Ciba-Geigy Ag Certain n-substituted butyramide derivatives
US4929641B1 (en) 1988-05-11 1994-08-30 Schering Corp Mercapto-acylamino acid antihypertensives
KR880007441A (ko) 1986-12-11 1988-08-27 알렌 제이.스피겔 스피로-치환된 글루타르아미드 이뇨제
FR2623498B1 (fr) 1987-11-24 1990-04-06 Bioprojet Soc Civ Nouveaux composes enantiomeres derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques
GB8820844D0 (en) 1988-09-05 1988-10-05 Pfizer Ltd Therapeutic agents
US5599951A (en) 1989-09-15 1997-02-04 Societe Civile Bioprojet Amino acid derivatives, the process for their preparation and their applications to therapy
US5294632A (en) 1991-05-01 1994-03-15 Ciba-Geigy Corporation Phosphono/biaryl substituted dipetide derivatives
US5155100A (en) 1991-05-01 1992-10-13 Ciba-Geigy Corporation Phosphono/biaryl substituted dipeptide derivatives
US5217996A (en) 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
US5508272A (en) 1993-06-15 1996-04-16 Bristol-Myers Squibb Company Compounds containing a fused bicycle ring and processes therefor
DE19510566A1 (de) 1995-03-23 1996-09-26 Kali Chemie Pharma Gmbh Benzazepin-, Benzoxazepin- und Benzothiazepin-N-essigsäurederivate sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
CA2218716A1 (en) 1995-04-21 1996-10-24 Novartis Ag N-aroylamino acid amides as endothelin inhibitors
US6660756B2 (en) 2001-03-28 2003-12-09 Pfizer Inc. N-phenpropylcyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
GB0119305D0 (en) 2001-04-12 2001-10-03 Aventis Pharma Gmbh Mercaptoacetylamide derivatives,a process for their preparation and their use
EP2385037A1 (en) * 2003-06-24 2011-11-09 Chemtura Corporation Fungicidal phenoxyphenylhydrazine derivatives
WO2006027680A1 (en) 2004-09-10 2006-03-16 Pfizer Limited 3-(1-carbamoylcyclohexyl) propionic acid derivatives as inhibitors of neutral endopeptidase enzyme
ATE429417T1 (de) * 2005-02-10 2009-05-15 Medivir Ab Hiv-protease-inhibitoren
AR057882A1 (es) 2005-11-09 2007-12-26 Novartis Ag Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra
WO2007106708A2 (en) 2006-03-10 2007-09-20 Novartis Ag Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril
KR101580067B1 (ko) 2007-01-12 2015-12-23 노파르티스 아게 5-바이페닐-4-아미노-2-메틸 펜탄산의 제조 방법
TWI448284B (zh) 2007-04-24 2014-08-11 Theravance Inc 雙效抗高血壓劑
PE20091364A1 (es) 2008-01-17 2009-10-13 Novartis Ag Proceso para la preparacion de inhibidores de nep
ME01923B (me) * 2009-05-28 2015-05-20 Novartis Ag Supstituisani derivati aminopropionske kiseline kao inhibitori neprilizina
SG176010A1 (en) * 2009-05-28 2011-12-29 Novartis Ag Substituted aminobutyric derivatives as neprilysin inhibitors
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
CN102712585B (zh) 2010-01-22 2015-06-24 诺华股份有限公司 中性内肽酶抑制剂中间体和其制备方法
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
US8993631B2 (en) 2010-11-16 2015-03-31 Novartis Ag Method of treating contrast-induced nephropathy
ES2548887T3 (es) 2010-12-15 2015-10-21 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
ES2550324T3 (es) 2010-12-15 2015-11-06 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
RU2604522C2 (ru) * 2011-02-17 2016-12-10 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи,ЭлЭлСи Замещенные аминомасляные производные в качестве ингибиторов неприлизина
EP2675792B1 (en) * 2011-02-17 2016-01-06 Theravance Biopharma R&D IP, LLC Substituted aminobutyric derivatives as neprilysin inhibitors
EP2714662B1 (en) 2011-05-31 2017-10-11 Theravance Biopharma R&D IP, LLC Neprilysin inhibitors
EP2714660B1 (en) 2011-05-31 2018-09-26 Theravance Biopharma R&D IP, LLC Neprilysin inhibitors
WO2012166389A1 (en) 2011-05-31 2012-12-06 Theravance, Inc. Neprilysin inhibitors
TWI560172B (en) 2011-11-02 2016-12-01 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
US9271965B2 (en) 2012-03-28 2016-03-01 Theravance Biopharma R&D Ip, Llc Crystalline forms of (R)-3-[N-(3'-chlorobiphenyl-4-ylmethyl)-N'-(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxyproprionic acid isopropyl ester
JP6088047B2 (ja) 2012-05-31 2017-03-01 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー 一酸化窒素ドナーであるネプリライシン阻害剤
US9108934B2 (en) 2012-06-08 2015-08-18 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
CA2873328A1 (en) 2012-06-08 2013-12-12 Theravance Biopharma R&D Ip, Llc Neprilysin inhibitors
NZ704741A (en) 2012-08-08 2017-10-27 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2726623C2 (ru) * 2015-02-11 2020-07-15 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи (2s,4r)-5-(5'-хлор-2'-фторбифенил-4-ил)-4-(этоксиоксалиламино)-2-гидроксиметил-2-метилпентановая кислота

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