RU2000109558A - COMBINATION OF THE 5-HT1A SELECTIVE ANTAGONIST AND THE H5-NT1B SELECTIVE ANTAGONIST OR PARTIAL AGONIST - Google Patents
COMBINATION OF THE 5-HT1A SELECTIVE ANTAGONIST AND THE H5-NT1B SELECTIVE ANTAGONIST OR PARTIAL AGONISTInfo
- Publication number
- RU2000109558A RU2000109558A RU2000109558/14A RU2000109558A RU2000109558A RU 2000109558 A RU2000109558 A RU 2000109558A RU 2000109558/14 A RU2000109558/14 A RU 2000109558/14A RU 2000109558 A RU2000109558 A RU 2000109558A RU 2000109558 A RU2000109558 A RU 2000109558A
- Authority
- RU
- Russia
- Prior art keywords
- component
- methylpiperazin
- tetrahydro
- paragraphs
- naphthyl
- Prior art date
Links
- 230000003042 antagnostic Effects 0.000 title claims 8
- 239000005557 antagonist Substances 0.000 title claims 8
- 239000004031 partial agonist Substances 0.000 title claims 5
- 102100002512 HTR1A Human genes 0.000 title 1
- 108060003344 HTR1A Proteins 0.000 title 1
- 239000000203 mixture Substances 0.000 claims 19
- 150000001875 compounds Chemical class 0.000 claims 13
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 5
- 239000011780 sodium chloride Substances 0.000 claims 5
- 239000002585 base Substances 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 239000012453 solvate Substances 0.000 claims 4
- IHDRUIHIJWCTIY-JOCHJYFZSA-N N-[(2R)-5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=C(C)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 IHDRUIHIJWCTIY-JOCHJYFZSA-N 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 201000008895 mood disease Diseases 0.000 claims 3
- 239000003727 serotonin 1A antagonist Substances 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 206010012378 Depression Diseases 0.000 claims 2
- XCSBGPAPGUIEFO-OAQYLSRUSA-N N-[(2R)-5-methoxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 XCSBGPAPGUIEFO-OAQYLSRUSA-N 0.000 claims 2
- HWSWMVFTXFBDRW-JOCHJYFZSA-N N-[(2R)-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 HWSWMVFTXFBDRW-JOCHJYFZSA-N 0.000 claims 2
- MQTUXRKNJYPMCG-CYBMUJFWSA-N Robalzotan Chemical compound C1CCC1N([C@H]1COC=2C(F)=CC=C(C=2C1)C(=O)N)C1CCC1 MQTUXRKNJYPMCG-CYBMUJFWSA-N 0.000 claims 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- GLCNLSFPYIMZJK-HXUWFJFHSA-N (2R)-5-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C([C@H](CC=12)C(=O)NC=3C=CC(=CC=3)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 GLCNLSFPYIMZJK-HXUWFJFHSA-N 0.000 claims 1
- JMQUFKWBATWTAM-HXUWFJFHSA-N (2R)-5-methoxy-8-(4-methylpiperazin-1-yl)-N-[2-(morpholine-4-carbonyl)phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C([C@H](CC=12)C(=O)NC=3C(=CC=CC=3)C(=O)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 JMQUFKWBATWTAM-HXUWFJFHSA-N 0.000 claims 1
- GLCNLSFPYIMZJK-FQEVSTJZSA-N (2S)-5-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C([C@@H](CC=12)C(=O)NC=3C=CC(=CC=3)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 GLCNLSFPYIMZJK-FQEVSTJZSA-N 0.000 claims 1
- XVMPHVYWWDVFAB-CQSZACIVSA-N (3R)-3-[cyclobutyl(cyclopentyl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound C1CCCC1N([C@H]1COC=2C(F)=CC=C(C=2C1)C(=O)N)C1CCC1 XVMPHVYWWDVFAB-CQSZACIVSA-N 0.000 claims 1
- AOSCUPVQGZCMHA-GFCCVEGCSA-N (3R)-3-[cyclobutyl(propan-2-yl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound CC(C)N([C@@H]1CC2=C(C(N)=O)C=CC(F)=C2OC1)C1CCC1 AOSCUPVQGZCMHA-GFCCVEGCSA-N 0.000 claims 1
- IAFNMDAKUNVLSN-GFCCVEGCSA-N (3R)-3-[cyclobutyl(propyl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound CCCN([C@@H]1CC2=C(C(N)=O)C=CC(F)=C2OC1)C1CCC1 IAFNMDAKUNVLSN-GFCCVEGCSA-N 0.000 claims 1
- JBRZRUJXYGBTBQ-CQSZACIVSA-N (3R)-3-[cyclohexyl(propyl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound CCCN([C@@H]1CC2=C(C(N)=O)C=CC(F)=C2OC1)C1CCCCC1 JBRZRUJXYGBTBQ-CQSZACIVSA-N 0.000 claims 1
- NDOVNYGZOLFRDL-CYBMUJFWSA-N (3R)-3-[cyclopentyl(propyl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound CCCN([C@@H]1CC2=C(C(N)=O)C=CC(F)=C2OC1)C1CCCC1 NDOVNYGZOLFRDL-CYBMUJFWSA-N 0.000 claims 1
- PBDYMMOBUALQNA-LLVKDONJSA-N (3R)-3-[tert-butyl(propyl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound C1=CC(C(N)=O)=C2C[C@@H](N(CCC)C(C)(C)C)COC2=C1F PBDYMMOBUALQNA-LLVKDONJSA-N 0.000 claims 1
- HDRGYUKRRPGJKR-LLVKDONJSA-N (3R)-8-fluoro-3-[propan-2-yl(propyl)amino]-3,4-dihydro-2H-chromene-5-carboxamide Chemical compound C1=CC(C(N)=O)=C2C[C@@H](N(C(C)C)CCC)COC2=C1F HDRGYUKRRPGJKR-LLVKDONJSA-N 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- NPFRXRWSLBQFJT-FQEVSTJZSA-N 4-N,4-N-dimethyl-1-N-[(3S)-8-methyl-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-chromen-3-yl]benzene-1,4-dicarboxamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C(=O)N[C@H]1CC2=C(N3CCN(C)CC3)C=CC(C)=C2OC1 NPFRXRWSLBQFJT-FQEVSTJZSA-N 0.000 claims 1
- OOEQHHKVTDYZTD-OAQYLSRUSA-N 4-morpholin-4-yl-N-[(2R)-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C([C@H](CC1=2)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC1=CC=CC=2N1CCNCC1 OOEQHHKVTDYZTD-OAQYLSRUSA-N 0.000 claims 1
- GLCNLSFPYIMZJK-UHFFFAOYSA-N 5-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1=2CC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)CCC=2C(OC)=CC=C1N1CCN(C)CC1 GLCNLSFPYIMZJK-UHFFFAOYSA-N 0.000 claims 1
- GGWPSJWVARDUIR-UHFFFAOYSA-N 8-methoxy-5-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)-3,4-dihydro-2H-chromene-3-carboxamide Chemical compound C1=2CC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)COC=2C(OC)=CC=C1N1CCN(C)CC1 GGWPSJWVARDUIR-UHFFFAOYSA-N 0.000 claims 1
- BSBVBFLNLYJFBZ-QGZVFWFLSA-N N-[(2R)-5-bromo-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCN1C1=CC=C(Br)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)C(F)(F)F)CC2 BSBVBFLNLYJFBZ-QGZVFWFLSA-N 0.000 claims 1
- BYJYPZAHTUBRNT-HXUWFJFHSA-N N-[(2R)-5-bromo-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=C(Br)C2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 BYJYPZAHTUBRNT-HXUWFJFHSA-N 0.000 claims 1
- OXZHFWAHGKDGDI-LJQANCHMSA-N N-[(2R)-5-bromo-8-piperazin-1-yl-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(Br)=CC=C2N1CCNCC1 OXZHFWAHGKDGDI-LJQANCHMSA-N 0.000 claims 1
- BEEWOAIWRLZBGZ-HSZRJFAPSA-N N-[(2R)-5-ethyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)N3CCOCC3)CC=1C(CC)=CC=C2N1CCN(C)CC1 BEEWOAIWRLZBGZ-HSZRJFAPSA-N 0.000 claims 1
- WZMSJJIAEOODBC-JOCHJYFZSA-N N-[(2R)-5-methoxy-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-(morpholine-4-carbonyl)benzamide Chemical compound C([C@H](CC=12)NC(=O)C=3C=CC(=CC=3)C(=O)N3CCOCC3)CC=1C(OC)=CC=C2N1CCN(C)CC1 WZMSJJIAEOODBC-JOCHJYFZSA-N 0.000 claims 1
- FTCLFWOUOUOQEH-HSZRJFAPSA-N N-[(2R)-8-(4-ethylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(CC)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CC2 FTCLFWOUOUOQEH-HSZRJFAPSA-N 0.000 claims 1
- VAAMBBBNNWFJHZ-FQEVSTJZSA-N N-[(3S)-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-chromen-3-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1C[C@H](NC(=O)C=1C=CC(=CC=1)N1CCOCC1)CO2 VAAMBBBNNWFJHZ-FQEVSTJZSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000000240 adjuvant Effects 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000004000 serotonin 1B antagonist Substances 0.000 claims 1
- 230000001225 therapeutic Effects 0.000 claims 1
Claims (22)
где R1 представляет собой н-пропил или циклобутил, R2 представляет собой изопропил, третичный бутил, циклобутил, циклопентил или циклогексил, R3 представляет собой водород, и R4 представляет собой водород или метил, и находящегося в форме R-энан-тиомера, со вторым компонентом (b), являющимся селективным антагонистом или частичным агонистом h5-HT1B, имеющим формулу II
где X представляет собой CH2, О;
Y представляет собой CONH, NHCO;
R1 представляет собой Н, (C1-С6)-алкил, (С3-С6) -циклоалкил;
R2 представляет собой Н, (C1-С6)-алкил, (C1-С6)-алкокси, галоген;
R3 представляет собой
-CF3, -C(O)NR4R5;
R4 и R5 независимо представляют собой Н или (C1-C4)-алкил, в виде рацемата, R-энантиомера или S-энантиомера, причем указанные компоненты (а) и (b) находятся в форме свободных оснований, их сольватов или фармацевтически приемлемых солей.1. The combination of the first component (a), which is a selective antagonist of 5-HT 1A , having the formula I
where R 1 represents n-propyl or cyclobutyl, R 2 represents isopropyl, tertiary butyl, cyclobutyl, cyclopentyl or cyclohexyl, R 3 represents hydrogen, and R 4 represents hydrogen or methyl, and in the form of R-enantiomer , with the second component (b) being a selective antagonist or partial agonist of h5-HT 1B having the formula II
where X represents CH 2 , O;
Y represents CONH, NHCO;
R 1 represents H, (C 1 -C 6 ) -alkyl, (C 3 -C 6 ) -cycloalkyl;
R 2 represents H, (C 1 -C 6 ) -alkyl, (C 1 -C 6 ) -alkoxy, halogen;
R 3 represents
-CF 3 , -C (O) NR 4 R 5 ;
R 4 and R 5 independently represent H or (C 1 -C 4 ) -alkyl in the form of a racemate, R-enantiomer or S-enantiomer, wherein said components (a) and (b) are in the form of free bases, their solvates or pharmaceutically acceptable salts.
(R)-3-(М-циклопентил-N-н-пропиламино)-8-фтор-5-метил-карбамоил-3,4-дигидро-2Н-1-бензопирана,
(R)-8-фтор-3-(N-изопропил-N-н-пропиламино)-5-карбамоил-3,4-дигидро-2Н-1-бензопирана,
(R)-5-карбамоил-3-(N-трет-бутил-N-н-пропиламино)-8-фтор-3,4-дигидро-2Н-1-бензопирана,
(R)-5-карбамоил-3-(N-циклобутил-N-пропиламино)-8-фтор-3,4-дигидро-2Н-1-бензопирана,
(R)-5-карбамоил-3-(N-циклобутил-N-изопропиламино)-8-фтор-3,4-дигидро-2Н-1-бензопирана, (R)-5-карбамоил-3-(N-циклопентил-N-н-пропиламино)-8-фтор-3,4-дигидро-2Н-1-бензопиран,
(R)-5-карбамоил-3-(N-циклогексил-N-н-пропиламино)-8-фтор-3,4-дигидро-2Н-1-бензопиран,
(R)-5-карбамоил-3-(N-циклопентил-N-циклобутиламино)-8-фтор-3,4-дигидро-2Н-1-бензопиран,
где указанное соединение может находиться в форме свободных оснований, сольватов или фармацевтически приемлемых солей.2. The combination according to claim 1, in which the first component (a) is a compound selected from
(R) -3- (M-cyclopentyl-N-n-propylamino) -8-fluoro-5-methyl-carbamoyl-3,4-dihydro-2H-1-benzopyran,
(R) -8-fluoro-3- (N-isopropyl-N-n-propylamino) -5-carbamoyl-3,4-dihydro-2H-1-benzopyran,
(R) -5-carbamoyl-3- (N-tert-butyl-N-n-propylamino) -8-fluoro-3,4-dihydro-2H-1-benzopyran,
(R) -5-carbamoyl-3- (N-cyclobutyl-N-propylamino) -8-fluoro-3,4-dihydro-2H-1-benzopyran,
(R) -5-carbamoyl-3- (N-cyclobutyl-N-isopropylamino) -8-fluoro-3,4-dihydro-2H-1-benzopyran, (R) -5-carbamoyl-3- (N-cyclopentyl -N-n-propylamino) -8-fluoro-3,4-dihydro-2H-1-benzopyran,
(R) -5-carbamoyl-3- (N-cyclohexyl-N-n-propylamino) -8-fluoro-3,4-dihydro-2H-1-benzopyran,
(R) -5-carbamoyl-3- (N-cyclopentyl-N-cyclobutylamino) -8-fluoro-3,4-dihydro-2H-1-benzopyran,
where the specified compound may be in the form of free bases, solvates or pharmaceutically acceptable salts.
(R)-N-[8-(пиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[8-(4-этилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[5-метокси-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[5-этил-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[5-этил-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -(4-морфолинокарбонил)бензамида;
(R)-N-[5-метокси-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинокарбонилбензамида; (R)-N-[5-бром-8-(пиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[5-бром-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
(R)-N-[5-бром-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-трифторметилбензамида;
(R)-N-[5-метил-8-(4-метилпиперазин-1-ил)-1,2,3,4-тетрагидро-2-нафтил] -4-морфолинобензамида;
N-(4-морфолинофенил)-8-(4-метилпиперазинил)-5-метокси-1,2,3,4-тетрагидронафталин-2-карбоксамида;
(R)-N-(4-морфолинофенил)-8-(4-метилпиперазинил)-5-метокси-1,2,3,4-тетрагидронафталин-2-карбоксамида;
(S)-N-(4-морфолинофенил)-8-(4-метилпиперазинил)-5-метокси-1,2,3,4-тетрагидронафталин-2-карбоксамида;
(R)-N-(морфолинокарбонилфенил)-8-(4-метилпиперазин-1-ил)-5-метокси-1,2,3,4-тетрагидронафталин-2-карбоксамида;
(S)-N-[5-(4-метилпиперазин-1-ил)-3,4-дигидро-2Н-1-бензопиран-3-ил] -4-морфолинобензамида;
(S)-N-[5-(4-метилпиперазин-1-ил)-3,4-дигидро-2Н-1-бензопиран-3-ил] -4-(4-пиперидон-1-ил)бензамида;
(S)-N-[8-метил-5-(4-метилпиперазин-1-ил)-3,4-дигидро-2Н-1-бензопиран-3-ил] -4-(диметиламинокарбонил)бензамида;
N-[4-(4-морфолинил)фенил] -8-метокси-5-(4-метилпиперазин-1-ил)-3,4-дигидро-2Н-1-бензопиран-3-карбоксамида, где указанные соединения могут находиться в форме свободных оснований, гидратов или фармацевтически приемлемых солей.8. The combination according to any one of paragraphs. 1-3, in which the second component (b) is a compound selected from
(R) -N- [8- (piperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [8- (4-ethylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [5-methoxy-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [5-ethyl-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [5-ethyl-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] - (4-morpholinocarbonyl) benzamide;
(R) -N- [5-methoxy-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinocarbonylbenzamide; (R) -N- [5-bromo-8- (piperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [5-bromo-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
(R) -N- [5-bromo-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-trifluoromethylbenzamide;
(R) -N- [5-methyl-8- (4-methylpiperazin-1-yl) -1,2,3,4-tetrahydro-2-naphthyl] -4-morpholinobenzamide;
N- (4-morpholinophenyl) -8- (4-methylpiperazinyl) -5-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxamide;
(R) -N- (4-morpholinophenyl) -8- (4-methylpiperazinyl) -5-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxamide;
(S) -N- (4-morpholinophenyl) -8- (4-methylpiperazinyl) -5-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxamide;
(R) -N- (morpholinocarbonylphenyl) -8- (4-methylpiperazin-1-yl) -5-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxamide;
(S) -N- [5- (4-methylpiperazin-1-yl) -3,4-dihydro-2H-1-benzopyran-3-yl] -4-morpholinobenzamide;
(S) -N- [5- (4-methylpiperazin-1-yl) -3,4-dihydro-2H-1-benzopyran-3-yl] -4- (4-piperidon-1-yl) benzamide;
(S) -N- [8-methyl-5- (4-methylpiperazin-1-yl) -3,4-dihydro-2H-1-benzopyran-3-yl] -4- (dimethylaminocarbonyl) benzamide;
N- [4- (4-morpholinyl) phenyl] -8-methoxy-5- (4-methylpiperazin-1-yl) -3,4-dihydro-2H-1-benzopyran-3-carboxamide, where these compounds may be in the form of free bases, hydrates or pharmaceutically acceptable salts.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9703374-0 | 1997-09-18 | ||
SE9703374A SE9703374D0 (en) | 1997-09-18 | 1997-09-18 | A new combination |
Publications (2)
Publication Number | Publication Date |
---|---|
RU2000109558A true RU2000109558A (en) | 2002-02-10 |
RU2215528C2 RU2215528C2 (en) | 2003-11-10 |
Family
ID=20408294
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU2000109558/14A RU2215528C2 (en) | 1997-09-18 | 1998-09-09 | Combination of selective antagonist of 5htia and selective antagonist or partial agonist of h5-htib |
Country Status (30)
Country | Link |
---|---|
US (1) | US6159972A (en) |
EP (1) | EP1021183B1 (en) |
JP (1) | JP2001516717A (en) |
KR (1) | KR20010024075A (en) |
CN (1) | CN1182847C (en) |
AR (1) | AR015447A1 (en) |
AT (1) | ATE261728T1 (en) |
AU (1) | AU752718B2 (en) |
BR (1) | BR9812234A (en) |
CA (1) | CA2302383A1 (en) |
DE (1) | DE69822490T2 (en) |
DK (1) | DK1021183T3 (en) |
EE (1) | EE04142B1 (en) |
ES (1) | ES2216307T3 (en) |
HK (1) | HK1032740A1 (en) |
HU (1) | HUP0100401A3 (en) |
IL (1) | IL134774A0 (en) |
IS (1) | IS5408A (en) |
MY (1) | MY116281A (en) |
NO (1) | NO20001398L (en) |
NZ (1) | NZ503174A (en) |
PL (1) | PL339370A1 (en) |
PT (1) | PT1021183E (en) |
RU (1) | RU2215528C2 (en) |
SE (1) | SE9703374D0 (en) |
SK (1) | SK2842000A3 (en) |
TR (1) | TR200000734T2 (en) |
TW (1) | TW568786B (en) |
WO (1) | WO1999013876A1 (en) |
ZA (1) | ZA987810B (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9601110D0 (en) | 1996-03-22 | 1996-03-22 | Astra Ab | Substituted 1,2,3,4-tetrahydronaphthalene derivatives |
WO2002066454A1 (en) * | 2001-02-21 | 2002-08-29 | Sankyo Company, Limited | Chromene derivatives |
US7504395B2 (en) * | 2001-07-20 | 2009-03-17 | Psychogenics, Inc. | Treatment for attention-deficit hyperactivity disorder |
US20050165025A1 (en) * | 2004-01-22 | 2005-07-28 | Recordati Ireland Ltd. | Combination therapy with 5HT 1A and 5HT 1B-receptor antagonists |
USD969017S1 (en) | 2021-06-28 | 2022-11-08 | Koninklijke Asscher Diamant Maatschappij B.V. | Rose marquise diamond article |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9410512D0 (en) * | 1994-05-25 | 1994-07-13 | Smithkline Beecham Plc | Novel treatment |
SE9501567D0 (en) * | 1995-04-27 | 1995-04-27 | Astra Ab | A new combination |
FI961247A0 (en) * | 1996-03-18 | 1996-03-18 | Finnish Peroxides Ab Oy | Foerfarande Foer loesning av uppsvaellningsproblem i en avfalls vattenreningsanordning Foer kontroll av traodartiga bakterier |
SE9601110D0 (en) * | 1996-03-22 | 1996-03-22 | Astra Ab | Substituted 1,2,3,4-tetrahydronaphthalene derivatives |
-
1997
- 1997-09-18 SE SE9703374A patent/SE9703374D0/en unknown
-
1998
- 1998-08-27 ZA ZA987810A patent/ZA987810B/en unknown
- 1998-08-29 TW TW087114345A patent/TW568786B/en not_active IP Right Cessation
- 1998-09-09 CA CA002302383A patent/CA2302383A1/en not_active Abandoned
- 1998-09-09 JP JP2000511498A patent/JP2001516717A/en active Pending
- 1998-09-09 EP EP98944374A patent/EP1021183B1/en not_active Expired - Lifetime
- 1998-09-09 US US09/171,581 patent/US6159972A/en not_active Expired - Fee Related
- 1998-09-09 TR TR2000/00734T patent/TR200000734T2/en unknown
- 1998-09-09 ES ES98944374T patent/ES2216307T3/en not_active Expired - Lifetime
- 1998-09-09 BR BR9812234-7A patent/BR9812234A/en not_active IP Right Cessation
- 1998-09-09 CN CNB988112493A patent/CN1182847C/en not_active Expired - Fee Related
- 1998-09-09 DK DK98944374T patent/DK1021183T3/en active
- 1998-09-09 RU RU2000109558/14A patent/RU2215528C2/en not_active IP Right Cessation
- 1998-09-09 PL PL98339370A patent/PL339370A1/en unknown
- 1998-09-09 AU AU91929/98A patent/AU752718B2/en not_active Ceased
- 1998-09-09 EE EEP200000143A patent/EE04142B1/en not_active IP Right Cessation
- 1998-09-09 DE DE69822490T patent/DE69822490T2/en not_active Expired - Fee Related
- 1998-09-09 NZ NZ503174A patent/NZ503174A/en unknown
- 1998-09-09 KR KR1020007002821A patent/KR20010024075A/en not_active Application Discontinuation
- 1998-09-09 HU HU0100401A patent/HUP0100401A3/en unknown
- 1998-09-09 IL IL13477498A patent/IL134774A0/en unknown
- 1998-09-09 WO PCT/SE1998/001600 patent/WO1999013876A1/en not_active Application Discontinuation
- 1998-09-09 SK SK284-2000A patent/SK2842000A3/en unknown
- 1998-09-09 AT AT98944374T patent/ATE261728T1/en not_active IP Right Cessation
- 1998-09-09 PT PT98944374T patent/PT1021183E/en unknown
- 1998-09-16 MY MYPI98004226A patent/MY116281A/en unknown
- 1998-09-17 AR ARP980104633A patent/AR015447A1/en unknown
-
2000
- 2000-03-15 IS IS5408A patent/IS5408A/en unknown
- 2000-03-17 NO NO20001398A patent/NO20001398L/en not_active Application Discontinuation
- 2000-11-22 HK HK00107467A patent/HK1032740A1/en not_active IP Right Cessation
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