RU2013133874A - Ингенол-3-ацилаты iii и ингенол-3-карбаматы - Google Patents

Ингенол-3-ацилаты iii и ингенол-3-карбаматы Download PDF

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RU2013133874A
RU2013133874A RU2013133874/04A RU2013133874A RU2013133874A RU 2013133874 A RU2013133874 A RU 2013133874A RU 2013133874/04 A RU2013133874/04 A RU 2013133874/04A RU 2013133874 A RU2013133874 A RU 2013133874A RU 2013133874 A RU2013133874 A RU 2013133874A
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ingenol
carboxylate
alkyl
methyl
compound according
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RU2013133874/04A
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RU2572549C2 (ru
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Гуннар ГРУЭ-СЕРЕНСЕН
Сифу Лян
Томас ХЕГБЕРТ
Кристоффер МОНССОН
Пер ВЕДСЕ
Томас ВИФИАН
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Лео Лэборетериз Лимитед
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Abstract

1. Соединение общей формулы Iгде R обозначает гетероарил, который может быть необязательно замещен одним или более заместителями, независимо выбранными из R7;или R обозначает гетероциклоалкил или гетероциклоалкенил, где указанный гетероциклоалкил или гетероциклоалкенил необязательно замещены одним или более заместителями, независимо выбранными из R8;или R обозначает X;R7 представляет галоген, циано или гидроксил;или R7 представляет (C-C)алкил, (C-C)алкенил, (C-C)циклоалкил, гетероциклоалкил, арил, гетероарил, арилалкил, гетероциклоалкилалкил или (C-C)циклоалкилалкил, где указанные (C-C)алкил, (C-C)алкенил, (C-C)циклоалкил, гетероциклоалкил, арил, гетероарил, арилалкил, гетероциклоалкилалкил или (C-C)циклоалкилалкил необязательно замещены одним или более заместителями, независимо выбранными из R9;или R7 представляет -NRaCORb, -CONRaRb, -COORc, -OCORa, -ORa, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -SRa или -NRaRb;R9 представляет галоген, циано, гидрокси, (C-C)алкил, галоген(C-C)алкил, -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa или =O;R8 представляет галоген, циано или гидроксил;или R8 представляет (C-C)алкил, (C-C)алкенил, арил, гетероарил, (C-C)циклоалкил или гетероциклоалкил, где указанные (C-C)алкил, (C-C)алкенил, арил, гетероарил, (C-C)циклоалкил или гетероциклоалкил необязательно замещены одним или более заместителями, независимо выбранными из R10,или R8 представляет -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa, =O, =N-ORa, -O-N=CRaRb, NRaRb или -C(O)N(Ra)O-Rb;R10 представляет галоген, циано, гидрокси, (C-C)алкил, (C-C)алкокси, галоген(C-C)алкил, галоген(C-C)алкокси, гидрокси(C-C)алкил, циано(C-C)алкил, арил, гетероарил, циклоалкил, гетероци�

Claims (46)

1. Соединение общей формулы I
Figure 00000001
где R обозначает гетероарил, который может быть необязательно замещен одним или более заместителями, независимо выбранными из R7;
или R обозначает гетероциклоалкил или гетероциклоалкенил, где указанный гетероциклоалкил или гетероциклоалкенил необязательно замещены одним или более заместителями, независимо выбранными из R8;
или R обозначает X;
R7 представляет галоген, циано или гидроксил;
или R7 представляет (C1-C4)алкил, (C2-C4)алкенил, (C3-C7)циклоалкил, гетероциклоалкил, арил, гетероарил, арилалкил, гетероциклоалкилалкил или (C3-C7)циклоалкилалкил, где указанные (C1-C4)алкил, (C2-C4)алкенил, (C3-C7)циклоалкил, гетероциклоалкил, арил, гетероарил, арилалкил, гетероциклоалкилалкил или (C3-C7)циклоалкилалкил необязательно замещены одним или более заместителями, независимо выбранными из R9;
или R7 представляет -NRaCORb, -CONRaRb, -COORc, -OCORa, -ORa, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -SRa или -NRaRb;
R9 представляет галоген, циано, гидрокси, (C1-C4)алкил, галоген(C1-C4)алкил, -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa или =O;
R8 представляет галоген, циано или гидроксил;
или R8 представляет (C1-C4)алкил, (C1-C4)алкенил, арил, гетероарил, (C3-C7)циклоалкил или гетероциклоалкил, где указанные (C1-C4)алкил, (C2-C4)алкенил, арил, гетероарил, (C3-C7)циклоалкил или гетероциклоалкил необязательно замещены одним или более заместителями, независимо выбранными из R10,
или R8 представляет -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa, =O, =N-ORa, -O-N=CRaRb, NRaRb или -C(O)N(Ra)O-Rb;
R10 представляет галоген, циано, гидрокси, (C1-C4)алкил, (C1-C4)алкокси, галоген(C1-C4)алкил, галоген(C1-C4)алкокси, гидрокси(C1-C4)алкил, циано(C1-C4)алкил, арил, гетероарил, циклоалкил, гетероциклоалкил, -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa или =O;
Ra и Rb представляют водород, (C1-C4)алкил, галоген(C1-C4)алкил, (C1-C4)алкокси(C1-C4)алкил, гидрокси(C1-C4)алкил, циано(C1-C4)алкил, арил, гетероарил, циклоалкил или гетероциклоалкил;
Rc представляет водород, (C1-C4)алкил, галоген(C1-C4)алкил, (C1-C4)алкокси(C1-C4)алкил, гидрокси(C1-Cx)алкил, циано(C1-Cx)алкил, арил, гетероарил, циклоалкил или гетероциклоалкил;
X представляет -NR11R12
где R11 и R12 независимо представляют водород,
или где R11 и R12 независимо представляют (C1-C6)алкил, (C2-C6)алкенил или (C2-C6)алкинил, циклоалкил, циклоалкенил, арил, гетероарил, гетероциклоалкил, гетероциклоалкенил, циклоалкилалкил, циклоалкенилалкил, арилалкил, гетероарилалкил, гетероциклоалкилалкил, гетероциклоалкенилалкил, алкилциклоалкил, алкилциклоалкенил, алкиларил, алкилгетероарил или алкилгетероциклоалкил, где указанные (C1-C6)алкил, (C2-C6)алкенил или (C2-C6)алкинил, циклоалкил, циклоалкенил, арил, гетероарил, гетероциклоалкил, гетероциклоалкенил, циклоалкилалкил, циклоалкенилалкил, арилалкил, гетероарилалкил, гетероциклоалкилалкил, гетероциклоалкенилалкил, алкилциклоалкил, алкилциклоалкенил, алкиларил, алкилгетероарил или алкилгетероциклоалкил необязательно замещены одним или более заместителями, независимо выбранными из R13;
R13 представляет галоген, циано или гидроксил,
или R13 представляет (C1-C4)алкил, (C2-C4)алкенил, арил, (C3-C7)циклоалкил, гетероарил или гетероциклоалкил, где указанные (C1-C4)алкил, (C2-C4)алкенил, арил, (C3-C7)циклоалкил, гетероарил или гетероциклоалкил необязательно замещены одним или более заместителями, независимо выбранными из R14
или R13 представляет -NRdCORe, -COORf, -OCORd, -CONRdRe, -OCONRdRe, -NRdCOORe, -NRdCONRdRe, -NRdSO2Re, -NRdSO2NRdRe, -SO2NRdRe, -SO2Rd, -S(O)Rd, -ORd, -SRd, =O, =N-ORd, -O-N=CRdRe, -NRdRe или -C(O)N(Rd)-Ore,
где Rd и Re независимо представляют водород, (C1-C4)алкил, галоген(C1-C4)алкил, (C1-C4)алкокси(C1-C4)алкил, гидрокси(C1-C4)алкил, циано(C1-C4)алкил, арил, гетероарил, циклоалкил или гетероциклоалкил;
Rf представляет водород, (C1-C4)алкил, галоген(C1-C4)алкил, (C1-C4)алкокси(C1-C4)алкил, гидрокси(C1-C4)алкил, циано(C1-C4)алкил, арил, гетероарил, циклоалкил или гетероциклоалкил;
R14 представляет водород, гидроксил, циано, (C1-C4)алкил, (C1-C4)алкокси, галоген(C1-C4)алкил, галоген(C1-C4)алкокси, гидрокси(C1-C4)алкил, циано(C1-C4)алкил, арил, гетероарил, циклоалкил, гетероциклоалкил, -NRdCORe, -COORf, -OCORd, -CONRdRe, -OCONRdRe, -NRdCOORe, -NRdCONRdRe, -NRdSO2Re, -NRdSO2NRdRe, -SO2NRdRe, -SO2Rd, -S(O)Rd, -ORd, -SRd или =O;
и его фармацевтически приемлемые соли, пролекарства, гидраты и сольваты.
2. Соединение по п.1, где R обозначает гетероарил, который может необязательно быть замещен одним или более заместителями, независимо выбранными из R7,
или R обозначает гетероциклоалкил или гетероциклоалкенил, каждый из которых может необязательно быть замещен одним или более заместителями, независимо выбранными из R8,
R7 представляет галоген, циано, гидрсил;
или R7 представляет (C1-C4)алкил, (C2-C4)алкенил, (C3-C7)циклоалкил, гетероциклоалкил, арил, гетероарил, каждый из которых необязательно замещен одним или более заместителями, независимо выбранными из R9;
или R7 представляет -NRaCORb, -CONRaRb, -COORc, -OCORa, -ORa, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -SRa;
R9 представляет галоген, циано, гидрокси (C1-C4)алкил, галоген(C1-C4)алкил, -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa, =O;
R8 представляет галоген, циано, гидроксил;
или R8 представляет (C1-C4)алкил, (C1-C4)алкенил, арил, гетероарил, (C3-C7)циклоалкил, гетероциклоалкил, каждый из которых необязательно замещен одним или более заместителями, независимо выбранными из R10,
или R8 представляет -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa, =O;
R10 представляет галоген, циано, гидрокси, (C1-C4)алкил, галоген(C1-C4)алкил, -NRaCORb, -COORc, -OCORa, -CONRaRb, -OCONRaRb, -NRaCOORb, -NRaCONRaRb, -NRaSO2NRaRb, -NRaSO2Rb, -SO2NRaRb, -SO2Ra, -S(O)Ra, -ORa, -SRa, =O;
Ra и Rb представляют водород, (C1-C4)алкил, галоген(C1-C4)алкил, (C1-C4)алкокси(C1-C4)алкил, гидрокси(C1-C4)алкил, циано(C1-C4)алкил;
Rc представляет (C1-C4)алкил, галоген(C1-C4)алкил, (C1-C4)алкокси(C1-C4)алкил, гидрокси(C1-C4)алкил, циано(C1-C4)алкил.
3. Соединение по п.1, где R обозначает гетероарил.
4. Соединение по п.3, где гетероарил представляет изоксазолил, пиридил, хинолил, изохинолил, индолил, фурил, тиазолил, имидазолил, пиразолил, оксазолил, тиенил, пиримидинил, 1,2,3-триазолил, индазолил, циннолил, 1,2-бензоксазолил, имидазотиазолил, имидазопиридинил, пирролил, изотиазолил, тетрагидроиндазолил или оксадиазолил.
5. Соединение по любому из пп.1-4, где R7 независимо выбран один или более раз из группы (C1-C4)алкила, (C2-C4)алкенила, арила, арилалкила, гетероциклоалкилалкила, (C3-C7)-циклоалкилалкила, (C3-C7)-циклоалкила, -COORc, -ORa или галогена.
6. Соединение по п.5, где R7 выбран из фенила, метила, этила, изопропила, т-бутила, пиперидила, трет-бутилоксикарбонила, бензила, тетрагидропиранилметила, -OCH3, циклопропила, аллила, циклопропилметила, Cl, Br или I.
7. Соединение по любому из пп.1-4, где R9 обозначает галоген, -ORa, (C1-C4)алкил или -SO2Ra.
8. Соединение по п.7, где R9 обозначает Cl, F, -OCH3, метил или метилсульфонил.
9. Соединение по п.1, где R обозначает гетероциклоалкил или гетероциклоалкенил.
10. Соединение по п.9, где гетероциклоалкил или гетероциклоалкенил представляет пирролидинил, пиперидинил, морфолинил, 5-оксабицикло[2.2.2]октанил, оксаспиро[4.5]дец-1-енил, оксотиазолил, дигидротиазолил, оксопиранил, азепанил, азабицикло[3.2.2]нонанил, бензоксазинил, хиноксалинил, изоиндолинил, дигидрохинолинил, индолинил или дигидрохиноксалинил.
11. Соединение по любому из пп.1, 2 или 9, где R8 обозначает (C1-C4)алкил, арил или =O.
12. Соединение по п.11, где R8 обозначает метил, фенил или =O.
13. Соединение по любому из пп.1, 2 или 9 где R10 представляет галоген.
14. Соединение по п.1, где R представляет -NR11R12.
15. Соединение по любому из пп.1 или 14, где R11 и R12 независимо представляют водород, (C1-C6)алкил, арил, циклоалкил, арилалкил, гетероарил, циклоалкилалкил, гетероарилалкил, гетероциклоалкил, гетероциклоалкилалкил, (C2-C6)алкенил или (C2-C6)алкинил.
16. Соединение по п.15, где R11 и R12 независимо представляют водород, метил, этил, изопропил, фенил, бензил, циклогексил, инданил, тетралинил, фенилэтил, циклопропилметил, пиразолил, изоксазолилметил, циклопентил, циклопропил, пиридил, пиперидил, тетрагидропиранилметил, тетрагидропиранил, циклобутил, аллил, пропинил или тиазолил.
17. Соединение по любому из пп.1 или 14, где R13 представляет (C1-C4)алкил, циано, галоген, =O, -ORa или -COORf.
18. Соединение по п.17, где R13 представляет метил, циано, F, =O, -OCH3 или -COOC(CH3)3.
19. Соединение по любому из пп.1 или 14, где R11 или R12 независимо представляет водород.
20. Соединение по любому из пп.1-4, 9 или 14, причем указанное соединение выбрано из группы, состоящей из:
Ингенол 3-(5-метил-3-фенилизоксазол-4-карбоксилат) или
Ингенол 3-(5-метил-3-(2-хлор-6-фторфенил)-изоксазол-4-карбоксилат),
Ингенол 3-(1S-камфанат),
Ингенол 3-(3-фенилтриазол-4-карбоксилат),
Ингенол 3-(2-фенилпиразол-3-карбоксилат),
Ингенол 3-(1-метилиндазол-3-карбоксилат),
Ингенол 3-(3-этил-5-метилизоксазол-4-карбоксилат),
Ингенол 3-(3-метил-5-метилизоксазол-4-карбоксилат),
Ингенол 3-(1-метилиндол-3-карбоксилат),
Ингенол 3-(3-фенилтиофен-2-карбоксилат),
Ингенол 3-(5-фенилизоксазол-3-карбоксилат),
Ингенол 3-(N-этил-карбамат),
Ингенол 3-(Н,Н-диметилкарбамат),
Ингенол 3-(морфолин-4-карбоксилат),
Ингенол 3-(пирролидин-1-карбоксилат),
Ингенол 3-(N-метил-N-фенилкарбамат),
Ингенол 3-(Н,Н-диэтилкарбамат),
Ингенол 3-(пиперидин-1-карбоксилат),
Ингенол 3-(N-бензил-N-метилкарбамат),
Ингенол 3-(N-циклогексил-N-метилкарбамат),
Ингенол 3-(N-циклогексилкарбамат),
Ингенол 3-(N-фенилкарбамат),
Ингенол 3-(N-(индан-1-ил)карбамат),
Ингенол 3-(3,3-диметилпиперидин-1-карбоксилат),
Ингенол 3-(N-метил-N-тетралин-1-ил-карбамат),
Ингенол 3-(N-(2-циано-1-метил-этил)-N-метилкарбамат),
Ингенол 3-(N-метил-N-((S)-1-фенэтил)карбамат),
Ингенол 3-(N-метил-N-(циклопропилметил)карбамат),
Ингенол 3-(изохинолин-1-карбоксилат),
Ингенол 3-(хинолин-4-карбоксилат),
Ингенол 3-(циннолин-4-карбоксилат),
Ингенол 3-(3-фенилимидазол-4-карбоксилат),
Ингенол 3-(5-фенилоксазол-4-карбоксилат),
Ингенол 3-(1,2-бензоксазол-3-карбоксилат),
Ингенол 3-(3-изопропил-5-метилизоксазол-4-карбоксилат),
Ингенол 3-(3-(2-метоксифенил)-5-метилизоксазол-4-карбоксилат),
Ингенол 3-(4-бром-2-метилпиразол-3-карбоксилат),
Ингенол 3-(4-бром-2-этилпиразол-3-карбоксилат),
Ингенол 3-(4-хлор-2-метилпиразол-3-карбоксилат),
Ингенол 3-(5-бромпиримидин-4-карбоксилат),
Ингенол 3-(3-бромпиридин-2-карбоксилат),
Ингенол 3-(5-метилтиазол-4-карбоксилат),
Ингенол 3-(4-хлор-1-метилпиразол-3-карбоксилат),
Ингенол 3-(2,4-диметилтиазол-5-карбоксилат),
Ингенол 3-(2,5-диметилоксазол-4-карбоксилат),
Ингенол 3-(2,4-диметилфуран-3-карбоксилат),
Ингенол 3-(3,5-диэтилизоксазол-4-карбоксилат),
Ингенол 3-(N-(3-фторфенил)-N-метилкарбамат),
Ингенол 3-(N-(2,5-диметилпиразол-3-ил)-N-метилкарбамат),
Ингенол 3-(1H-индол-7-карбоксилат),
Ингенол 3-(2-трет-бутил-5-метилпиразол-3-карбоксилат),
Ингенол 3-(5-трет-бутил-2-метилпиразол-3-карбоксилат),
Ингенол 3-(6-метилимидазо[2,1-b]тиазол-5-карбоксилат),
Ингенол 3-(2-метилимидазо[1,2-a]пиридин-3-карбоксилат),
Ингенол 3-(2,4,5-триметилфуран-3-карбоксилат),
Ингенол 3-(3-метилтиофен-2-карбоксилат),
Ингенол 3-(2-метил-4-(1-пиперидил)пиразол-3-карбоксилат),
Ингенол 3-(2-хлор-5-изопропил-тиазол-4-карбоксилат),
Ингенол 3-(4-хлор-2,5-диметилпиразол-3-карбоксилат),
Ингенол 3-(1,2,4-триметилпиррол-3-карбоксилат),
Ингенол 3-(1,3,5-триметилпиррол-2-карбоксилат),
Ингенол 3-(1-этил-3,5-диметилпиррол-2-карбоксилат),
Ингенол 3-(1-трет-бутилоксикарбонил-3,3-диметилпирролидин-2-карбоксилат),
Ингенол 3-((2S)-1-фенилпирролидин-2-карбоксилат),
Ингенол 3-(1-изопропил-3,5-диметилпиразол-4-карбоксилат),
Ингенол 3-(5-этил-3-изопропил-изоксазол-4-карбоксилат),
Ингенол 3-(2-метилиндазол-3-карбоксилат),
Ингенол 3-(5-метил-3-трет-бутилизоксазол-4-карбоксилат),
Ингенол 3-(2-метил-3-оксо-4-оксаспиро[4.5]дец-1-ен-1-карбоксилат),
Ингенол 3-(1-трет-бутил-3,5-диметилпиразол-4-карбоксилат),
Ингенол 3-(3,5-диметилизотиазол-4-карбоксилат),
Ингенол 3-(5-йод-3-метил-изотиазол-4-карбоксилат),
Ингенол 3-(4-(4-метоксифенил)-2-метилпиразол-3-карбоксилат),
Ингенол 3-(4-(2-метилфенил)-2-метилпиразол-3-карбоксилат),
Ингенол 3-(2-метил-4-(4-метилсульфонилфенил)пиразол-3-карбоксилат),
Ингенол 3-(2-метил-4-фенилпиразол-3-карбоксилат),
Ингенол 3-(3,5-диметил-1-фенилпиразол-4-карбоксилат),
Ингенол 3-(1,5-диметил-3-фенилпиразол-4-карбоксилат),
Ингенол 3-(1-бензил-3,5-диметилпиразол-4-карбоксилат),
Ингенол 3-(3,5-диметил-1-(тетрагидропиран-4-илметил)пиразол-4-карбоксилат),
Ингенол 3-(4-метил-2-оксо-3H-тиазол-5-карбоксилат),
Ингенол 3-(2-метил-4,5,6,7-тетрагидроиндазол-3-карбоксилат),
Ингенол 3-(1,2-диметилиндол-3-карбоксилат),
Ингенол 3-(5-метокси-1,2-диметилиндол-3-карбоксилат),
Ингенол 3-(1,3,5-триметилпиразол-4-карбоксилат),
Ингенол 3-(4-метил-1,2,5-оксадиазол-3-карбоксилат),
Ингенол 3-(2-метокси-4-метилтиазол-5-карбоксилат),
Ингенол 3-(4,5-диметилизоксазол-3-карбоксилат),
Ингенол 3-(4-бром-1-метилпиразол-3-карбоксилат),
Ингенол 3-(1,3-диметилиндол-2-карбоксилат),
Ингенол 3-(5-метокси-1,3-диметилиндол-2-карбоксилат),
Ингенол 3-(2,4-диметил-6-оксопиран-3-карбоксилат),
Ингенол 3-(1-метил-3-фенилиндол-2-карбоксилат),
Ингенол 3-(3-метил-5-(трифторметил)изоксазол-4-карбоксилат),
Ингенол 3-(1,3-диметилпиррол-2-карбоксилат),
Ингенол 3-(3,5-диметил-1-(2,2,2-трифторэтил)пиразол-4-карбоксилат),
Ингенол 3-(1-циклопропил-2,5-диметилпиррол-3-карбоксилат),
Ингенол 3-(1,2,5-триметилпиррол-3-карбоксилат),
Ингенол 3-(2,4-диметил-1H-пиррол-3-карбоксилат),
Ингенол 3-(1-метилпиррол-2-карбоксилат),
Ингенол 3-(4-метил-1H-пиррол-2-карбоксилат),
Ингенол 3-(1,5-диметилпиррол-2-карбоксилат),
Ингенол 3-(3-метил-1H-пиррол-2-карбоксилат),
Ингенол 3-(1-циклопропилпиррол-2-карбоксилат),
Ингенол 3-(1-этил-2,4-диметилпиррол-3-карбоксилат),
Ингенол 3-(1-аллил-2,4-диметилпиррол-3-карбоксилат),
Ингенол 3-(1-(циклопропилметил)-2,4-диметилпиррол-3-карбоксилат),
Ингенол 3-(1-(2-метоксиэтил)-2,4-диметилпиррол-3-карбоксилат),
Ингенол 3-(N-(3,5-диметилизоксазол-4-ил)-N-метилкарбамат),
Ингенол 3-(N-(1,5-диметилпиразол-3-ил)-N-метилкарбамат),
Ингенол 3-(N-циклопентил-N-метилкарбамат),
Ингенол 3-(N-циклопропил-N-метилкарбамат),
Ингенол 3-(N-метил-N-(2-пиридил)карбамат),
Ингенол 3-(4-оксо-2,3-дигидрохинолин-1-карбоксилат),
Ингенол 3-(3,4-дигидро-2H-хинолин-1-карбоксилат),
Ингенол 3-(индолин-1-карбоксилат),
Ингенол 3-(азепан-1-карбоксилат),
Ингенол 3-(N-(4-хлорфенил)-N-метилкарбамат),
Ингенол 3-(N-(4-фторфенил)-N-метилкарбамат),
Ингенол 3-(N-метил-N-(2-метоксифенил)карбамат),
Ингенол 3-(N-метил-N-(2-метилфенил)карбамат),
Ингенол 3-(3-оксо-2,4-дигидрохиноксалин-1-карбоксилат),
Ингенол 3-(N-этил-N-фенилкарбамат),
Ингенол 3-(2-трифторметилпирролидин-1-карбоксилат),
Ингенол 3-(3-азабицикло[3.2.2]нонан-3-карбоксилат),
Ингенол 3-(2,3-дигидро-1,4-бензоксазин-4-карбоксилат),
Ингенол 3-(N-(2-фторфенил)-N-метилкарбамат),
Ингенол 3-(3-метил-2,3-дигидро-1,4-бензоксазин-4-карбоксилат),
Ингенол 3-(2-трифторметилпирролидин-1-карбоксилат) (изомер A),
Ингенол 3-(2-трифторметилпирролидин-1-карбоксилат) (изомер B),
Ингенол 3-(N-метил-N-(N-(трет-бутилоксикарбонил)-4-пиперидил)карбамат),
Ингенол 3-(N-метил-N-(3-метилфенил)карбамат),
Ингенол 3-(3,4-дигидро-2H-хиноксалин-1-карбоксилат),
Ингенол 3-(изоиндолин-2-карбоксилат),
Ингенол 3-(N-метил-N-(тетрагидропиран-4-илметил)карбамат),
Ингенол 3-(N-метил-N-(тетрагидропиран-4-ил)карбамат),
Ингенол 3-(N-метил-N-(3-метоксифенил)карбамат),
Ингенол 3-(N-циклобутил-N-метилкарбамат),
Ингенол 3-(N-аллил-N-метилкарбамат),
Ингенол 3-(N-метил-N-проп-2-инилкарбамат),
Ингенол 3-(N-метил-N-(4-метилтиазол-2-ил)карбамат) или
Ингенол 3-(N-(4-цианофенил)-N-метилкарбамат).
21. Соединение по любому из пп.1-4, 9 или 14 для применения в качестве лекарственного препарата при лечении.
22. Соединение по любому из пп.1-4, 9 или 14 для применения при лечении, предотвращении, облегчении течения или профилактике физиологических расстройств или заболеваний, связанных с гиперплазией или неоплазией.
23. Соединение по п.22, где расстройство или заболевание выбрано из кожных бородавок, генитальных бородавок, актинового кератоза, плоскоклеточной карциномы (SCC), базальноклеточной карциномы (BCC), злокачественного лентиго, внутриэпителиальной неоплазии шейки матки, анальной внутриэпителиальной неоплазии или внутриэпителиальной неоплазии вульвы.
24. Применение соединения по любому из пп.1-4, 9 или 14 для получения фармацевтического лекарственного препарата.
25. Применение соединения по п.24 для получения лекарственного препарата для лечения, облегчения течения или профилактики физиологических расстройств или заболеваний, связанных с гиперплазией или неоплазией.
26. Применение по п.25, где расстройство или заболевание выбрано из кожных бородавок, генитальных бородавок, плоскоклеточной карциномы (SCC), базальноклеточной карциномы (BCC), злокачественного лентиго, внутриэпителиальной неоплазии шейки матки, анальной внутриэпителиальной неоплазии или внутриэпителиальной неоплазии вульвы.
27. Способ предотвращения, лечения, облегчения течения или профилактики физиологических расстройств или заболеваний, связанных с гиперплазией или неоплазией, введением нуждающемуся в нем индивиду соединения по любому из пп.1-4, 9 или 14.
28. Способ по п.27, где расстройство или заболевание выбрано из кожных бородавок, генитальных бородавок, плоскоклеточной карциномы (SCC), базальноклеточной карциномы (BCC), злокачественного лентиго, внутриэпителиальной неоплазии шейки матки, анальной внутриэпителиальной неоплазии или внутриэпителиальной неоплазии вульвы.
29. Соединение по любому из пп.1-4, 9 или 14 для применения при лечении или облегчении течения заболеваний или расстройств по косметическим показаниям.
30. Соединение по п.29, где косметическое показание выбрано из фотоповреждения кожи или себоррейного кератоза.
31. Применение соединения по п.24 для получения лекарственного препарата для лечения или облегчения течения заболеваний или расстройств по косметическим показаниям.
32. Применение по п.31, где косметическое показание выбрано из фотоповреждения кожи или себоррейного кератоза.
33. Способ лечения или облегчения течения заболеваний или расстройств по косметическим показаниям введением нуждающемуся в нем индивиду соединения по любому из пп.1-4, 9 или 14.
34. Способ по п.33, где косметическое показание выбрано из фотоповреждения кожи или себоррейного кератоза.
35. Применение соединения по п.24 при получении фармацевтической композиции для лечения или облегчения течения заболевания, расстройства или состояния, реагирующего на стимуляцию окислительного выброса нейтрофилов.
36. Применение соединения по п.24 при получении фармацевтической композиции для лечения или облегчения течения заболевания, расстройства или состояния, реагирующего на стимуляцию высвобождения IL-8 из кератиноцитов.
37. Применение соединения по п.24 при получении фармацевтической композиции для лечения или облегчения течения заболевания, расстройства или состояния, реагирующего на индукцию некроза.
38. Способ предотвращения, лечения, облегчения течения или профилактики физиологического заболевания или расстройства, реагирующего на стимуляцию окислительного выброса нейтрофилов, введением нуждающемуся в нем индивиду соединения по любому из пп.1-4, 9 или 14.
39. Способ предотвращения, лечения, облегчения течения или профилактики физиологического заболевания или расстройства, реагирующего на стимуляцию высвобождения IL-8 из кератиноцитов, введением нуждающемуся в нем индивиду соединения по любому из пп.1-4, 9 или 14.
40. Способ предотвращения, лечения, облегчения течения или профилактики физиологического заболевания или расстройства, реагирующего на индукцию некроза, введением нуждающемуся в нем индивиду соединения по любому из пп.1-4, 9 или 14.
41. Соединение по любому из пп.1-4, 9 или 14 для применения при лечении или облегчении течения заболевания, расстройства или состояния, реагирующего на стимуляцию окислительного выброса нейтрофилов.
42. Соединение по любому из пп.1-4, 9 или 14 для применения при лечении или облегчении течения заболевания, расстройства или состояния, реагирующего на стимуляцию высвобождения IL-8 из кератиноцитов.
43. Соединение по любому из пп.1-4, 9 или 14 для применения при лечении или облегчении течения заболевания, расстройства или состояния, реагирующего на индукцию некроза.
44. Фармацевтическая композиция, содержащая соединение по любому из пп.1-4, 9 или 14, или его фармацевтически приемлемый стереоизомер, соль или гидролизируемый in vivo сложный эфир, вместе с фармацевтически приемлемым носителем или эксципиентом.
45. Фармацевтическая композиция по п.44, где композиция подходит для топического введения.
46. Фармацевтическая композиция, содержащая соединение по любому из пп.1-4, 9 или 14, или его фармацевтически приемлемый стереоизомер, соль или гидролизируемый in vivo сложный эфир, в комбинации с одним или более других терапевтически активных средств.
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