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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Russia
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formula
compound
independently
hydrogen
defined above
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RU99115750/04A
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Russian (ru)
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RU2193029C2 (en
Inventor
Даниель ДЕЛОРМ
Эдвард Робертс
Жонгйонг ВЕЙ
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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
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Publication of RU99115750A publication Critical patent/RU99115750A/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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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA008826B1 (en) * 2002-07-03 2007-08-31 Х. Лундбекк А/С Secondary amino anilinic piperidines as mch1 antagonists and uses thereof

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9504661D0 (en) 1995-12-22 1995-12-22 Astra Pharma Inc New compounds
TW548271B (en) 1996-12-20 2003-08-21 Astra Pharma Inc Novel piperidine derivatives having an exocyclic double bond with analgesic effects
SE9604786D0 (en) * 1996-12-20 1996-12-20 Astra Pharma Inc New compounds
US6436959B1 (en) 1998-12-23 2002-08-20 Ortho-Mcneil Pharmaceutical, Inc. 4-[aryl(piperidin-4-yl)]aminobenzamides
US6677332B1 (en) 1999-05-25 2004-01-13 Sepracor, Inc. Heterocyclic analgesic compounds and methods of use thereof
US7361666B2 (en) 1999-05-25 2008-04-22 Sepracor, Inc. Heterocyclic analgesic compounds and methods of use thereof
AU777760B2 (en) * 1999-05-25 2004-10-28 Sepracor, Inc. Heterocyclic analgesic compounds and methods of use thereof
US6635661B2 (en) 2000-05-25 2003-10-21 Sepracor Inc. Heterocyclic analgesic compounds and methods of use thereof
SE9904673D0 (en) 1999-12-20 1999-12-20 Astra Pharma Inc Novel compounds
SE9904674D0 (en) 1999-12-20 1999-12-20 Astra Pharma Inc Novel compounds
US6306876B1 (en) 1999-12-22 2001-10-23 Ortho-Mcneil Pharmaceutical, Inc. 4-[aryl(8-azabicyclo[3.2.1]octan-3-yl)]aminobenzoic acid derivatives
DE60112725T2 (en) * 2000-02-18 2006-06-01 Meiji Seika Kaisha Ltd. PHENOXYALKYLAMINE DERIVATIVES AS AGONISTS OF THE OPIOID DELTA RECEPTOR
BR0108965A (en) 2000-03-03 2002-11-26 Ortho Mcneil Pharm Inc Derivatives of 3- (diarylmethylene) -8-azabicyclo [3,2,1] octane
AU4274401A (en) 2000-03-24 2001-10-03 Meiji Seika Kaisha Diphenylalkylamine derivatives useful as opioid delta receptor agonists
SE0001209D0 (en) * 2000-04-04 2000-04-04 Astrazeneca Canada Inc Novel compounds
SE0001207D0 (en) * 2000-04-04 2000-04-04 Astrazeneca Canada Inc Novel compounds
SE0001208D0 (en) * 2000-04-04 2000-04-04 Astrazeneca Canada Inc Novel compounds
WO2001092226A1 (en) 2000-05-25 2001-12-06 Sepracor, Inc. Heterocyclic analgesic compounds and method of use thereof
US6887876B2 (en) 2000-12-14 2005-05-03 Ortho-Mcneil Pharmaceutical, Inc. Benzamidine derivatives
SE0101765D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0101770D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0101773D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0101771D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0101768D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
NZ539828A (en) 2001-05-18 2007-01-26 Astrazeneca Ab 4 (phenyl-piperazinyl-methyl) benzamide derivatives and their use for the treatment of pain, anxiety or gastrointestinal disorders
SE0101766D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0101767D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0101769D0 (en) * 2001-05-18 2001-05-18 Astrazeneca Ab Novel compounds
SE0103313D0 (en) * 2001-10-03 2001-10-03 Astrazeneca Ab Novel compounds
KR100898562B1 (en) 2001-10-15 2009-05-20 얀센 파마슈티카 엔.브이. Novel substituted 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives and their use as selective non-peptide delta opioid agonists
US8575169B2 (en) 2001-10-29 2013-11-05 Versi Group, Llc Method of treating sexual dysfunctions with delta opioid receptor agonist compounds
US8476280B2 (en) * 2002-05-09 2013-07-02 Versi Group, Llc Compositions and methods for combating lower urinary tract dysfunctions with delta opioid receptor agonists
SE0203300D0 (en) 2002-11-07 2002-11-07 Astrazeneca Ab Novel Compounds
SE0203301D0 (en) * 2002-11-07 2002-11-07 Astrazeneca Ab Novel Compounds
SE0203303D0 (en) 2002-11-07 2002-11-07 Astrazeneca Ab Novel Compounds
SE0203302D0 (en) 2002-11-07 2002-11-07 Astrazeneca Ab Novel Compounds
SE0300103D0 (en) * 2003-01-16 2003-01-16 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
SE0300105D0 (en) * 2003-01-16 2003-01-16 Astrazeneca Ab Diarylmethylidene piperdine derivatives, preparations thereof and uses thereof
SE0300104D0 (en) * 2003-01-16 2003-01-16 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
SE0300987D0 (en) * 2003-04-03 2003-04-03 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
BRPI0409570A (en) * 2003-04-15 2006-04-18 Pfizer Prod Inc 3-benzhydrylidene-8-aza-bicyclo [3.2.1] octane derivatives with opioid receptor activity
SE0301441D0 (en) * 2003-05-16 2003-05-16 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
SE0301442D0 (en) * 2003-05-16 2003-05-16 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations therof and uses thereof
RU2005136524A (en) * 2003-05-16 2006-06-27 Астразенека Аб (Se) DIARYLMETHYLIDENIPIPERIDINE DERIVATIVES, METHODS FOR THEIR PRODUCTION AND USE
SE0301445D0 (en) * 2003-05-16 2003-05-16 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
SE0301443D0 (en) * 2003-05-16 2003-05-16 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
EP1626044A4 (en) * 2003-05-20 2008-08-20 Ajinomoto Kk Novel piperidine derivative
EA015491B1 (en) * 2003-06-27 2011-08-30 Янссен Фармацевтика Н.В. Tricyclic delta opioid modulators
KR20060066070A (en) * 2003-07-28 2006-06-15 스미스클라인 비참 코포레이션 Cycloalkylidene compounds as modulators of estrogen receptor
JP4976134B2 (en) 2003-10-01 2012-07-18 アドラー コーポレーション Spirocyclic heterocyclic derivatives and methods of using them
SE0400025D0 (en) * 2004-01-09 2004-01-09 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
SE0400026D0 (en) * 2004-01-09 2004-01-09 Astrazeneca Ab Diarylmethylidene piperidine derivatives, preparations thereof and uses thereof
US7435822B2 (en) 2004-02-03 2008-10-14 Janssen Pharmaceutica N.V. 3-(diheteroarylmethylene)-8-azabicyclo[3.2.1]octane and 3-((aryl)(heteroaryl)methylene)-8-azabicyclo[3.2.1]octane derivatives
MX2007001240A (en) 2004-08-02 2007-03-23 Astrazeneca Ab Diarylmethyl piperazine derivatives, preparations thereof and uses thereof.
KR20080027216A (en) 2004-08-05 2008-03-26 얀센 파마슈티카 엔.브이. TRICYCLIC delta;-OPIOID MODULATORS
SE0402485D0 (en) * 2004-10-13 2004-10-13 Astrazeneca Ab Polymorph of N, N-Diethyl-4- (3-Fluorophenyl-Piperidin-4-Ylidene-Methyl) -Benzamide Hydrochloride Salt
CA2591963A1 (en) 2004-12-22 2006-06-29 Janssen Pharmaceutica N.V. Tricyclic o-opioid modulators
KR20070087675A (en) * 2004-12-22 2007-08-28 얀센 파마슈티카 엔.브이. TRICYCLIC delta;-OPIOID MODULATORS
AU2006203880A1 (en) 2005-01-06 2006-07-13 Janssen Pharmaceutica N.V. Tricyclic delta-opioid modulators
US7557875B2 (en) 2005-03-22 2009-07-07 Industrial Technology Research Institute High performance flexible display with improved mechanical properties having electrically modulated material mixed with binder material in a ratio between 6:1 and 0.5:1
US7683168B2 (en) * 2005-04-14 2010-03-23 Mount Cook Bio Sciences, Inc. Compositions of novel opioid compounds and method of use thereof
WO2006138528A2 (en) 2005-06-16 2006-12-28 Janssen Pharmaceutica N.V Tricyclic opioid modulators
US7576207B2 (en) 2006-04-06 2009-08-18 Adolor Corporation Spirocyclic heterocyclic derivatives and methods of their use
US20080058949A1 (en) * 2006-09-06 2008-03-06 Roger Ryan Dees Implants with Transition Surfaces and Related Processes
MY148880A (en) * 2006-10-20 2013-06-14 Astrazeneca Ab N-(2-hydroxyethyl)-n-methyl-4-(quinolin-8-yl(1-(thiazol-4-ylmethyl)piperidin-4-ylidene)methyl)benzamide, the process of making it as well as its use for the treatment of pain, anxiety and depression
BRPI0820091B1 (en) 2007-12-06 2018-02-06 Shell Internationale Research Maatschappij B.V. Process for the preparation of an alkylene glycol from alkylene oxide
CN108139623A (en) * 2015-06-02 2018-06-08 康宁股份有限公司 Aesthetic surface and the display equipment with this surface
CN111825654A (en) * 2019-04-19 2020-10-27 北京酷瓴生物技术有限公司 Phenylmethylene piperidine derivatives, preparation method, intermediates and uses thereof

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2898339A (en) * 1957-07-29 1959-08-04 Wm S Merrell Co N-substituted benzhydrol, benzhydryl, and benzhydrylidene piperidine
US4581171A (en) * 1983-07-27 1986-04-08 Janssen Pharmaceutica, N.V. [[Bis(aryl)methylene]-1-piperidinyl]alkyl-pyrimidinones useful for treating psychotropic disorders
US4816586A (en) * 1987-07-29 1989-03-28 Regents Of The University Of Minnesota Delta opioid receptor antagonists
US5140029A (en) * 1989-01-09 1992-08-18 Janssen Pharmaceutica N.V. 2-aminopyrimidinone derivatives
US4939137A (en) * 1989-06-28 1990-07-03 Ortho Pharmaceutical Corporation Ring-fused thienopyrimidinedione derivatives
US5683998A (en) * 1991-04-23 1997-11-04 Toray Industries, Inc. Tricyclic triazolo derivatives, processes for producing the same and the uses of the same
GB9202238D0 (en) * 1992-02-03 1992-03-18 Wellcome Found Compounds
US5574159A (en) * 1992-02-03 1996-11-12 Delta Pharmaceuticals, Inc. Opioid compounds and methods for making therefor
SE9504661D0 (en) 1995-12-22 1995-12-22 Astra Pharma Inc New compounds
SE9604786D0 (en) * 1996-12-20 1996-12-20 Astra Pharma Inc New compounds
TW548271B (en) * 1996-12-20 2003-08-21 Astra Pharma Inc Novel piperidine derivatives having an exocyclic double bond with analgesic effects
CA2316341A1 (en) 1997-12-24 1999-07-08 Ortho-Mcneil Pharmaceutical, Inc. 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor
SE0001207D0 (en) * 2000-04-04 2000-04-04 Astrazeneca Canada Inc Novel compounds
SE0001208D0 (en) * 2000-04-04 2000-04-04 Astrazeneca Canada Inc Novel compounds

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA008826B1 (en) * 2002-07-03 2007-08-31 Х. Лундбекк А/С Secondary amino anilinic piperidines as mch1 antagonists and uses thereof

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