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RU99115750A - NEW CONNECTIONS WITH AN ANALYZING EFFECT - Google Patents

NEW CONNECTIONS WITH AN ANALYZING EFFECT

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Publication number
RU99115750A
RU99115750A RU99115750/04A RU99115750A RU99115750A RU 99115750 A RU99115750 A RU 99115750A RU 99115750/04 A RU99115750/04 A RU 99115750/04A RU 99115750 A RU99115750 A RU 99115750A RU 99115750 A RU99115750 A RU 99115750A
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RU
Russia
Prior art keywords
formula
compound
independently
hydrogen
defined above
Prior art date
Application number
RU99115750/04A
Other languages
Russian (ru)
Other versions
RU2193029C2 (en
Inventor
Даниель ДЕЛОРМ
Эдвард Робертс
Жонгйонг ВЕЙ
Original Assignee
АСТРА ФАРМА Инк.
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Priority claimed from SE9604785A external-priority patent/SE9604785D0/en
Priority claimed from SE9702535A external-priority patent/SE9702535D0/en
Application filed by АСТРА ФАРМА Инк. filed Critical АСТРА ФАРМА Инк.
Publication of RU99115750A publication Critical patent/RU99115750A/en
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Publication of RU2193029C2 publication Critical patent/RU2193029C2/en

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Claims (1)

1. Соединение общей формулы (I)
Figure 00000001

где R1 выбирают из водорода, разветвленного или неразветвленного C1-C6-алкила, C1-C6-алкенила, C3-C8-циклоалкила, C4-C8-(алкилциклоалкила), где алкил представляет C1-C2-алкил, и циклоалкил представляет C3-C6-циклоалкил;
C6-C10-арила или гетероарила, имеющего от 5 до 10 атомов, выбранных из С, S, N и О; где арил или гетероарил может быть необязательно и независимо замещен 1 или 2 заместителями, независимо выбранными из водорода, CH3, -(CH2)pCF3, галогена, -CONR5R4, -COOR5, -COR5, -(CH2)pNR5R4, -(СН2)pСН3(СН2)pSОR5R4, -(CH2)pSO2R5 и -(CH2)pSO2NR5, где R4 и R5, каждый независимо такие, как определено выше для R1, и р равно 0, 1 или 2;
(C1-C2-алкил)-(C6-C10-арила) или (C1-C2-алкил)гетероарила, причем гетероарильные части имеют от 5 до 10 атомов, выбранных из С, S, N и О, и где арил или гетероарил может быть необязательно и независимо замещен 1 или 2 заместителями, независимо выбранными из водорода, CH3, -(CH2)qCF3, галогена, -CONR5R4, -COOR5, -COR5, -(CH2)qNR5R4, -(CH2)qCH3(CH2)qSOR5R4,
-(CH2)qSO2R5, -(CH2)qSO2NR5 и -(CH2)pOR5, где R4 и R5, каждый независимо, такой, как определено выше для R1, и q равно 0, 1 или 2; и
Figure 00000002

Figure 00000003

Figure 00000004

где R18, R19, R20, R21, R22, R23, R24 и R25, каждый независимо, представляют водород, C1-C6-алкил или C1-C6-алкенил;
R2 и R3, каждый независимо, представляют водород или C1-C6-алкил;
А выбирают из
Figure 00000005

Figure 00000006

Figure 00000007

Figure 00000008

Figure 00000009

Figure 00000010

где R8, R9, R10, R11, R12, R13, R14, R15, R16 и R17, каждый независимо, такие как определено выше для R1, и где фенильное кольцо каждого заместителя А может быть необязательно и независимо замещено по любому положению фенильного кольца 1 или 2 заместителями Z1 и Z2, которые, каждый независимо, выбирают из водорода, CH3, -(CH2)qCF3, галогена, -CONR6R7, -COOR6, -COR6, -(CH2)rNR6R7, -(СН2)rСН3(СН2)rSОR6, -(CH2)rSO2R6 и -(CH2)rSO2NR6R7, где R6 и R7, каждый независимо, такие, как определено выше для R1, и r равно 0, 1 или 2;
Q представляет C5-C6-гидроарильный или гетерогидроароматический радикал, имеющий 5 или 6 атомов, выбранных из С, S, N и O; C5-C6-циклоалкил или гетероциклоалкил, имеющий 5 или 6 атомов, выбранных из С, S, N и O; и где каждый Q необязательно может быть замещен заместителем Z1 и Z2, как определено выше;
В представляет замещенную или незамещенную ароматическую, гетероароматическую, гидроароматическую или гетерогидроароматическую часть, имеющую от 5 до 10 атомов, выбранных из С, S, N и О, и необязательно и независимо замещенную 1 или 2 заместителями, независимо выбранными из водорода, CH3, -(CH2)tCF3, галогена, -(CH2)tCONR5R4, -(CH2)tNR5R4, -(CH2)tCOR5,
-(CH2)tCOOR5, -OR5, -(СН2)tSОR5, -(CH2)tSO2R5 и -(CH2)tSO2NR5R4, где R4 и R5, каждый независимо, такие, как определено выше для R1, и t равно 0, 1, 2 или 3; и
R4 и R5, каждый независимо, такие, как определено выше для R1,
а также фармацевтически приемлемые соли соединений формулы (I) и их изомеры, гидраты, изоформы и пролекарства.1. The compound of General formula (I)
Figure 00000001

where R 1 is selected from hydrogen, branched or unbranched C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl, C 3 -C 8 -cycloalkyl, C 4 -C 8 - (alkylcycloalkyl), where alkyl represents C 1 - C 2 -alkyl, and cycloalkyl is C 3 -C 6 -cycloalkyl;
C 6 -C 10 -aryl or heteroaryl having from 5 to 10 atoms selected from C, S, N and O; wherein aryl or heteroaryl may be optionally and independently substituted with 1 or 2 substituents independently selected from hydrogen, CH 3 , - (CH 2 ) p CF 3 , halogen, -CONR 5 R 4 , -COOR 5 , -COR 5 , - ( CH 2 ) p NR 5 R 4 , - (CH 2 ) p CH 3 (CH 2 ) p SOR 5 R 4 , - (CH 2 ) p SO 2 R 5 and - (CH 2 ) p SO 2 NR 5 , where R 4 and R 5 are each independently as defined above for R 1 , and p is 0, 1 or 2;
(C 1 -C 2 -alkyl) - (C 6 -C 10 -aryl) or (C 1 -C 2 -alkyl) heteroaryl, the heteroaryl moieties having from 5 to 10 atoms selected from C, S, N and O , and where aryl or heteroaryl may be optionally and independently substituted with 1 or 2 substituents independently selected from hydrogen, CH 3 , - (CH 2 ) q CF 3 , halogen, -CONR 5 R 4 , -COOR 5 , -COR 5 , - (CH 2 ) q NR 5 R 4 , - (CH 2 ) q CH 3 (CH 2 ) q SOR 5 R 4 ,
- (CH 2 ) q SO 2 R 5 , - (CH 2 ) q SO 2 NR 5 and - (CH 2 ) p OR 5 , where R 4 and R 5 , each independently, is as defined above for R 1 , and q is 0, 1, or 2; and
Figure 00000002

Figure 00000003

Figure 00000004

where R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 and R 25 each independently represent hydrogen, C 1 -C 6 alkyl or C 1 -C 6 alkenyl;
R 2 and R 3 each independently represent hydrogen or C 1 -C 6 alkyl;
And choose from
Figure 00000005

Figure 00000006

Figure 00000007

Figure 00000008

Figure 00000009

Figure 00000010

where R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 , each independently, such as defined above for R 1 , and where the phenyl ring of each substituent A can be optionally and independently substituted at any position of the phenyl ring 1 or 2 by the substituents Z 1 and Z 2 , which are each independently selected from hydrogen, CH 3 , - (CH 2 ) q CF 3 , halogen, —CONR 6 R 7 , - COOR 6 , -COR 6 , - (CH 2 ) r NR 6 R 7 , - (CH 2 ) r CH 3 (CH 2 ) r SOR 6 , - (CH 2 ) r SO 2 R 6 and - (CH 2 ) r SO 2 NR 6 R 7 where R 6 and R 7 are each independently such as defined above for R 1 and r is 0, 1 or 2;
Q represents a C 5 -C 6 -hydroaryl or heterohydroaromatic radical having 5 or 6 atoms selected from C, S, N and O; C 5 -C 6 -cycloalkyl or heterocycloalkyl having 5 or 6 atoms selected from C, S, N and O; and wherein each Q may optionally be substituted with a substituent Z 1 and Z 2 as defined above;
B represents a substituted or unsubstituted aromatic, heteroaromatic, hydroaromatic or heterohydroaromatic part having from 5 to 10 atoms selected from C, S, N and O and optionally and independently substituted with 1 or 2 substituents independently selected from hydrogen, CH 3 , - (CH 2 ) t CF 3 , halogen, - (CH 2 ) t CONR 5 R 4 , - (CH 2 ) t NR 5 R 4 , - (CH 2 ) t COR 5 ,
- (CH 2 ) t COOR 5 , -OR 5 , - (CH 2 ) t SOR 5 , - (CH 2 ) t SO 2 R 5 and - (CH 2 ) t SO 2 NR 5 R 4 , where R 4 and R 5 is each independently as defined above for R 1 , and t is 0, 1, 2 or 3; and
R 4 and R 5 each independently are as defined above for R 1 ,
as well as pharmaceutically acceptable salts of the compounds of formula (I) and their isomers, hydrates, isoforms, and prodrugs. 2. Соединение формулы (I) по п. 1, где
А выбирают из
Figure 00000011

Figure 00000012

Figure 00000013

Figure 00000014

Figure 00000015

Figure 00000016

где R8, R9, R10, R11, R12, R13, R14, R15, R16 и R17, каждый независимо, такие как определено выше для R1, и где фенильное кольцо каждого заместителя А может быть необязательно и независимо замещено по любому положению фенильного кольца 1 или 2 заместителями Z1 и Z2, которые, каждый независимо, выбирают из водорода, CH3, -(CH2)qCF3, галогена, -CONR6R7, -COOR6, -COR6, -(СН2)rNR6R7, -(CH2)rCH3(CH2)rSOR6, -(CH2)rSO2R6 и -(CH2)rSO2NR6R7, где R6 и R7, каждый независимо, такие, как определено выше для R1, и r равно 0, 1 или 2;
Q выбирают из морфолина, пиперидина и пирролидина; R1, R4 и R5, каждый независимо, выбирают из водорода, разветвленного или неразветвленного С1-С4-алкила, С3-С5-циклоалкила, С4-С8-(алкилциклоалкила), где алкил представляет С1-С2-алкил, и циклоалкил представляет С3-С6-циклоалкил; С6-С10-арила и гетероарила, имеющего от 5 до 6 атомов, выбранных из С, S, N и О; и где арил или гетероарил может быть необязательно и независимо замещен 1 или 2 заместителями, независимо выбранными из водорода, CH3, -(CH2)pCF3, галогена, -CONR5R4, -COOR5, -COR5, -(CH2)pNR5R4, -(CH2)pCH3(CH2)pSOR5R4,
-(CH2)pSO2R5 и -(CH2)pSO2NR5, где R4 и R5, каждый независимо, такие, как определено выше для R1, и р равно 0, 1 или 2;
В выбирают из фенила, нафтила, индолила, бензофуранила, дигидробензофуранила, бензотиофенила, пиррила, фуранила, хинолинила, изохинолинила, циклогексила, циклогексенила, циклопентила, циклопентенила, инданила, инденила, тетрагидронафтила, тетрагидрохинила, тетрагидроизохинолинила, тетрагидрофуранила, пирролидинила и индазолинила, каждый из которых необязательно и независимо замещен 1 или 2 заместителями, независимо выбранными из водорода, CH3, CF3, галогена, -(CH2)qCONR5R4, -(CH2)qNR5R4, -(CH2)qCOR5,
-C(CH2)qCO2R5 и -OR5, где q равно 0 или 1, и где R4 и R5 такие, как определено выше;
R2 и R3, каждый независимо, представляют водород или метил.2. The compound of formula (I) according to claim 1, where
And choose from
Figure 00000011

Figure 00000012

Figure 00000013

Figure 00000014

Figure 00000015

Figure 00000016

where R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 , each independently, such as defined above for R 1 , and where the phenyl ring of each substituent A can be optionally and independently substituted at any position of the phenyl ring 1 or 2 by the substituents Z 1 and Z 2 , which are each independently selected from hydrogen, CH 3 , - (CH 2 ) q CF 3 , halogen, —CONR 6 R 7 , - COOR 6 , -COR 6 , - (CH 2 ) r NR 6 R 7 , - (CH 2 ) r CH 3 (CH 2 ) r SOR 6 , - (CH 2 ) r SO 2 R 6 and - (CH 2 ) r SO 2 NR 6 R 7 where R 6 and R 7 are each independently such as defined above for R 1 and r is 0, 1 or 2;
Q is selected from morpholine, piperidine and pyrrolidine; R 1 , R 4 and R 5 are each independently selected from hydrogen, branched or unbranched C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, C 4 -C 8 - (alkylcycloalkyl), where alkyl is C 1 -C 2 -alkyl, and cycloalkyl is C 3 -C 6 -cycloalkyl; C 6 -C 10 -aryl and heteroaryl having from 5 to 6 atoms selected from C, S, N and O; and where aryl or heteroaryl may be optionally and independently substituted with 1 or 2 substituents independently selected from hydrogen, CH 3 , - (CH 2 ) p CF 3 , halogen, -CONR 5 R 4 , -COOR 5 , -COR 5 , - (CH 2 ) p NR 5 R 4 , - (CH 2 ) p CH 3 (CH 2 ) p SOR 5 R 4 ,
- (CH 2 ) p SO 2 R 5 and - (CH 2 ) p SO 2 NR 5 , where R 4 and R 5 , each independently, are as defined above for R 1 , and p is 0, 1 or 2;
In the past, in the world optionally and independently substituted with 1 or 2 substituents independently selected from hydrogen, CH 3 , CF 3 , halogen, - (CH 2 ) q CONR 5 R 4 , - (CH 2 ) q NR 5 R 4 , - (CH 2 ) q COR 5 ,
—C (CH 2 ) q CO 2 R 5 and —OR 5 , where q is 0 or 1, and where R 4 and R 5 are as defined above;
R 2 and R 3 each independently represent hydrogen or methyl. 3. Соединение формулы (I) по п. 2, где А представляет
Figure 00000017

где R8 и R9, оба представляют этил, и где фенильное кольцо необязательно и независимо, может быть замещено по любому положению фенильного кольца двумя заместителями Z1 и Z2, которые, каждый независимо, выбирают из водорода, CH3, -(CH2)qCF3, галогена, -CONR6R7, -COOR6, -COR6, -(CH2)rNR6R7,
-(СН2)rСН3(СН2)rSОR6, -(CH2)rSO2R6 и -(CH2)rSO2NR6R7, где R6 и R7, каждый независимо, такие, как определено выше для R1, и r равно 0, 1 или 2;
R1 выбирают из водорода, метила, этила, -CH2CH=CH2, -CH2-циклопропила, -CH2-арила или CH2-гетероарила, причем гетероарильные части имеют от 5 до 6 атомов, выбранных из С, S, N и О;
В выбирают из фенила, нафтила, индолила, бензофуранила, дигидробензофуранила, бензотиофенила, фуранила, хинолинила, изохинолинила, циклогексила, циклогексенила, циклопентила, циклопентенила, инданила, инденила, тетрагидронафтила, тетрагидрохинила, тетрагидроизохинолинила, тетрагидрофуранила и индазолинила, каждый из которых необязательно и независимо замещен 1 или 2 заместителями, независимо выбранными из водорода, СН3, СF3, галогена, -(CH2)qCONR5R4, -(CH2)qNR5R4, -(CH2)qCOR5, -(CH2)qCO2R5 и -OR5, где q равно 0 или 1, и где R4 и R5 такие, как определено выше;
R2 и R3, каждый независимо, представляет водород или метил.3. The compound of formula (I) according to claim 2, wherein A is
Figure 00000017

where R 8 and R 9 both represent ethyl, and where the phenyl ring may optionally and independently be substituted at any position of the phenyl ring by two substituents Z 1 and Z 2 , which are each independently selected from hydrogen, CH 3 , - (CH 2 ) q CF 3 , halogen, -CONR 6 R 7 , -COOR 6 , -COR 6 , - (CH 2 ) r NR 6 R 7 ,
- (CH 2 ) r CH 3 (CH 2 ) r SOR 6 , - (CH 2 ) r SO 2 R 6 and - (CH 2 ) r SO 2 NR 6 R 7 , where R 6 and R 7 are each independently, as defined above for R 1 , and r is 0, 1 or 2;
R 1 is selected from hydrogen, methyl, ethyl, -CH 2 CH = CH 2 , -CH 2 -cyclopropyl, -CH 2 -aryl or CH 2 -heteroaryl, and the heteroaryl moieties have from 5 to 6 atoms selected from C, S , N and O;
In the case of the fenon 1 or 2 substituents independently selected from hydrogen, CH 3 , CF 3 , halogen, - (CH 2 ) q CONR 5 R 4 , - (CH 2 ) q NR 5 R 4 , - (CH 2 ) q COR 5 , - (CH 2 ) q CO 2 R 5 and -OR 5 , where q is 0 or 1, and where R 4 and R 5 are as defined above;
R 2 and R 3 each independently represents hydrogen or methyl. 4. Соединение формулы (I) по п. 1, которое представляет собой
Figure 00000018

Figure 00000019

Figure 00000020

Figure 00000021

Figure 00000022

Figure 00000023

Figure 00000024

Figure 00000025

Figure 00000026

Figure 00000027

Figure 00000028

Figure 00000029

Figure 00000030

Figure 00000031

Figure 00000032

Figure 00000033

Figure 00000034

Figure 00000035

Figure 00000036

Figure 00000037

Figure 00000038

Figure 00000039

Figure 00000040

Figure 00000041

Figure 00000042

Figure 00000043

Figure 00000044

Figure 00000045

Figure 00000046

Figure 00000047

Figure 00000048

Figure 00000049

Figure 00000050

Figure 00000051

Figure 00000052

Figure 00000053

Figure 00000054

Figure 00000055

Figure 00000056

Figure 00000057

Figure 00000058

Figure 00000059

Figure 00000060

Figure 00000061

Figure 00000062

Figure 00000063

Figure 00000064

Figure 00000065

Figure 00000066

Figure 00000067

R представляет морфолин, пиперидин или пирролидин
Figure 00000068

Figure 00000069

Figure 00000070

Figure 00000071

Figure 00000072

Figure 00000073

Figure 00000074

Figure 00000075

Figure 00000076

Figure 00000077

5. Соединение по п.1, которое выбирают из
Figure 00000078

и
Figure 00000079

6. Соединение по любому из предыдущих пунктов в форме его гидрохлоридной, сульфатной, тартратной или цитратной соли.4. The compound of formula (I) according to claim 1, which is
Figure 00000018

Figure 00000019

Figure 00000020

Figure 00000021

Figure 00000022

Figure 00000023

Figure 00000024

Figure 00000025

Figure 00000026

Figure 00000027

Figure 00000028

Figure 00000029

Figure 00000030

Figure 00000031

Figure 00000032

Figure 00000033

Figure 00000034

Figure 00000035

Figure 00000036

Figure 00000037

Figure 00000038

Figure 00000039

Figure 00000040

Figure 00000041

Figure 00000042

Figure 00000043

Figure 00000044

Figure 00000045

Figure 00000046

Figure 00000047

Figure 00000048

Figure 00000049

Figure 00000050

Figure 00000051

Figure 00000052

Figure 00000053

Figure 00000054

Figure 00000055

Figure 00000056

Figure 00000057

Figure 00000058

Figure 00000059

Figure 00000060

Figure 00000061

Figure 00000062

Figure 00000063

Figure 00000064

Figure 00000065

Figure 00000066

Figure 00000067

R is morpholine, piperidine or pyrrolidine
Figure 00000068

Figure 00000069

Figure 00000070

Figure 00000071

Figure 00000072

Figure 00000073

Figure 00000074

Figure 00000075

Figure 00000076

Figure 00000077

5. The compound according to claim 1, which is chosen from
Figure 00000078

and
Figure 00000079

6. The compound according to any one of the preceding paragraphs in the form of its hydrochloride, sulphate, tartrate or citrate salt. 7. Соединение по любому из пп.1-6 для использования в терапии. 7. The compound according to any one of claims 1 to 6 for use in therapy. 8. Соединение по п. 7, где терапия представляет собой устранение боли. 8. The compound of claim 7, wherein therapy is the elimination of pain. 9. Соединение по п. 7, где терапия направлена на желудочно-кишечные нарушения. 9. The compound according to claim 7, wherein the therapy is directed to gastrointestinal disturbances. 10. Соединение по п. 7, где терапия направлена на спинные повреждения. 10. The compound of claim 7, wherein the therapy is directed to spinal injuries. 11. Соединение по п. 7, где терапия направлена на нарушения симпатической нервной системы. 11. The compound according to claim 7, where the therapy is aimed at disorders of the sympathetic nervous system. 12. Использование соединения формулы (I) по п. 1 для производства лекарственного средства для использования при лечении боли. 12. The use of the compound of formula (I) according to claim 1 for the manufacture of a medicament for use in the treatment of pain. 13. Использование соединения формулы (I) по п. 1 для производства лекарственного средства для использования при лечении желудочно-кишечных нарушений. 13. The use of the compound of formula (I) according to claim 1 for the manufacture of a medicament for use in the treatment of gastrointestinal disorders. 14. Использование соединения формулы (I) по п. 1 для производства лекарственного средства для использования при лечении спинных повреждений. 14. The use of the compound of formula (I) according to claim 1 for the manufacture of a medicament for use in the treatment of spinal injuries. 15. Соединение по любому из пп. 1-7, дополнительно, отличающееся тем, что оно мечено изотопом. 15. The compound according to any one of paragraphs. 1-7, additionally, characterized in that it is labeled with an isotope. 16. Использование соединения по п. 15 в качестве диагностического агента. 16. The use of compounds according to claim 15 as a diagnostic agent. 17. Меченое изотопом соединение формулы (I) по п. 1. 17. An isotope-labeled compound of formula (I) of claim 1. 18. Диагностический агент, включающий соединение формулы (I) по п. 1. 18. Diagnostic agent comprising a compound of formula (I) according to claim 1. 19. Фармацевтическая композиция, включающая соединение формулы (I) по п. 1 в качестве активного ингредиента вместе с фармакологически и фармацевтически приемлемым носителем. 19. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 as an active ingredient together with a pharmacologically and pharmaceutically acceptable carrier. 20. Способ получения соединения формулы (I) по п. 1, включающий
а) взаимодействие кетона формулы (l)
Figure 00000080

где R1, R2 и R3 такие, как определено в формуле (1) в п. 1, и Х представляет уходящую группу, с металлорганическим реагентом формулы (j) или (k)
Figure 00000081

Figure 00000082

где А и В такие, как определено в формуле (I) в п. 1, и М представляет группу металла; и где взаимодействие необязательно проводят в присутствии растворителя, с получением соединения формулы (h)
Figure 00000083

где А, В, R1, R2 и R3 такие, как определено в формуле (I) в п. 1, и где R1 может быть также трет-бутоксикарбонилом;
b) дегидратацию соединения формулы (h) с получением соединения формулы (I) по п. 1.20. A method of obtaining a compound of formula (I) according to claim 1, comprising
a) the interaction of the ketone of the formula (l)
Figure 00000080

where R 1 , R 2 and R 3 are as defined in formula (1) in claim 1, and X represents a leaving group, with an organometallic reagent of formula (j) or (k)
Figure 00000081

Figure 00000082

where a and b are as defined in formula (I) in claim 1, and M represents a metal group; and where the interaction is optionally carried out in the presence of a solvent, to obtain the compounds of formula (h)
Figure 00000083

where a, b, R 1 , R 2 and R 3 such as defined in formula (I) in claim 1, and where R 1 may also be tert-butoxycarbonyl;
b) dehydrating the compound of formula (h) to obtain the compound of formula (I) in accordance with claim 1. 21. Соединение формулы
Figure 00000084

где А, В, R2 и R3 такие, как определено в формуле (I) в п. 1.21. The compound of the formula
Figure 00000084

where A, B, R 2 and R 3 are as defined in formula (I) in claim 1. 22. Соединение формулы (h) по п. 21, где А представляет
Figure 00000085

где R8 и R9, оба представляют этильную группу, и Z1 и Z2 такие, как определено в п. 1.22. The compound of formula (h) according to claim 21, wherein A is
Figure 00000085

where R 8 and R 9 both represent an ethyl group, and Z 1 and Z 2 are as defined in claim 1. 23. Соединение по п. 22, которое представляет собой:
Figure 00000086

Figure 00000087

Figure 00000088

Figure 00000089

Figure 00000090

Figure 00000091

Figure 00000092

Figure 00000093

Figure 00000094

24. Способ лечения боли, включающий введение эффективного количества соединения формулы (I) по п. 1 субъекту, нуждающемуся в устранении боли.23. The compound according to claim 22, which is:
Figure 00000086

Figure 00000087

Figure 00000088

Figure 00000089

Figure 00000090

Figure 00000091

Figure 00000092

Figure 00000093

Figure 00000094

24. A method of treating pain, comprising administering an effective amount of a compound of formula (I) of claim 1 to a subject in need of elimination of pain. 25. Способ лечения желудочно-кишечных нарушений, включающий введение эффективного количества соединения формулы (I) по п. 1 субъекту, страдающему упомянутым желудочно-кишечным нарушением. 25. A method of treating gastrointestinal disorders, comprising administering an effective amount of a compound of formula (I) of claim 1 to a subject suffering from said gastrointestinal disorder. 26. Способ лечения спинных повреждений, включающий введение эффективного количества соединения формулы (I) по п. 1 субъекту, страдающему упомянутым спинным повреждением. 26. A method of treating spinal injuries, comprising administering an effective amount of a compound of formula (I) of claim 1 to a subject suffering from said spinal injury.
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