PL438130A1 - Derivatives of 5-substituted-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, method of their preparation and their applicatione - Google Patents
Derivatives of 5-substituted-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, method of their preparation and their applicationeInfo
- Publication number
- PL438130A1 PL438130A1 PL438130A PL43813021A PL438130A1 PL 438130 A1 PL438130 A1 PL 438130A1 PL 438130 A PL438130 A PL 438130A PL 43813021 A PL43813021 A PL 43813021A PL 438130 A1 PL438130 A1 PL 438130A1
- Authority
- PL
- Poland
- Prior art keywords
- sub
- substituent
- hydrogen
- methoxy
- ethoxy
- Prior art date
Links
- -1 5-substituted-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole Chemical class 0.000 title abstract 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract 7
- 239000001257 hydrogen Substances 0.000 abstract 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 abstract 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract 3
- 208000020925 Bipolar disease Diseases 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 abstract 2
- 239000002904 solvent Substances 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 abstract 1
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 abstract 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 abstract 1
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical class O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 abstract 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 abstract 1
- 208000028683 bipolar I disease Diseases 0.000 abstract 1
- 208000025307 bipolar depression Diseases 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 238000004587 chromatography analysis Methods 0.000 abstract 1
- 238000004440 column chromatography Methods 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- 239000008367 deionised water Substances 0.000 abstract 1
- 229910021641 deionized water Inorganic materials 0.000 abstract 1
- 229960003638 dopamine Drugs 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000002244 precipitate Substances 0.000 abstract 1
- 208000020016 psychiatric disease Diseases 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- 201000000980 schizophrenia Diseases 0.000 abstract 1
- 229940076279 serotonin Drugs 0.000 abstract 1
- 239000000741 silica gel Substances 0.000 abstract 1
- 229910002027 silica gel Inorganic materials 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Przedmiotem wynalazku są pochodne 5-podstawione-3-(1-benzylometylo-1,2,3,6-tetrahydropirydyn-4-ylo)-1H-indolu o wzorze ogólnym 1, gdzie R<sub>1</sub> oznacza podstawnik 2-fluorobenzylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik 3-fluorobenzylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik 4-fluorobenzylowy, natomiast R<sub>2</sub> oznacza podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik 2-metoksybenzylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik pirydyn-3-ylometylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik pirydyn-4-ylometylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik 2-chlorobenzylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik 3-chlorobenzylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowy lub podstawnik etoksylowy, R<sub>1</sub> oznacza podstawnik 4-chlorobenzylowy, natomiast R<sub>2</sub> oznacza wodór lub podstawnik metoksylowi. Związki będące przedmiotem wynalazku o wzorze ogólnym 1 otrzymuje się w reakcji 5-podstawionych indoli z 1-arylometylopodstawionymi pochodnymi piperydyn-4-onu korzystnie w metanolu lub etanolu korzystnie w obecności wodorotlenku potasu lub sodu. Reakcję prowadzi się przez korzystnie 18 godzin w temperaturze wrzenia rozpuszczalnika. Mieszaninę reakcyjną wylewa się do wody dejonizowanej i pozostawia na 48 godzin do swobodnej krystalizacji lub oziębia się, a po ochłodzeniu otrzymuje się osad produktu. Produkt reakcji oczyszcza się przez przemycie wodą, metanolem, eterem i rekrystalizuje się z odpowiedniego rozpuszczalnika, korzystnie metanolu lub DMF albo oczyszcza metodami chromatograficznymi, korzystnie za pomocą chromatografii kolumnowej (żel krzemionkowy gradient 2-5% bezw., NH<sub>3</sub> w MeOH/DCM). Związki będące przedmiotem wynalazku są wielocelowymi ligandami monoamin, w szczególności receptora dopaminowego D<sub>2</sub> oraz receptorów serotoninowych 5-HT<sub>1A</sub> i 5-HT<sub>2A</sub>, do zastosowania w leczeniu chorób psychicznych w szczególności schizofrenii, choroby afektywnej dwubiegunowej i depresji.The subject of the invention are 5-substituted-3-(1-benzylmethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives of the general formula 1, where R<sub>1</sub> is a substituent 2-fluorobenzyl and R<sub>2</sub> is hydrogen or methoxy or ethoxy, R<sub>1</sub> is 3-fluorobenzyl and R<sub>2</sub> is hydrogen or a methoxy substituent or an ethoxy substituent, R<sub>1</sub> is a 4-fluorobenzyl substituent and R<sub>2</sub> is an ethoxy substituent, R<sub>1</sub> is a 2-methoxybenzyl substituent and R<sub>2</sub> is hydrogen or methoxy or ethoxy, R<sub>1</sub> is pyridin-3-ylmethyl and R<sub>2</sub> is hydrogen or a methoxy substituent or an ethoxy substituent, R<sub>1</sub> represents a pyridin-4-ylmethyl substituent and R<sub>2</sub> represents a hydrogen substituent or a methoxy substituent or an ethoxy substituent, R<sub>1</sub > means base 2-chlorobenzyl and R<sub>2</sub> is hydrogen or methoxy or ethoxy, R<sub>1</sub> is 3-chlorobenzyl and R<sub>2</sub> is hydrogen or methoxy or ethoxy, R<sub>1</sub> is 4-chlorobenzyl and R<sub>2</sub> is hydrogen or methoxy. The compounds of the invention of general formula I are obtained by reacting 5-substituted indoles with 1-arylmethyl-substituted piperidin-4-one derivatives, preferably in methanol or ethanol, preferably in the presence of potassium or sodium hydroxide. The reaction is carried out for preferably 18 hours at the reflux temperature of the solvent. The reaction mixture is poured into deionized water and allowed to crystallize freely for 48 hours or cooled to give a precipitate on cooling. The reaction product is purified by washing with water, methanol, ether and recrystallized from a suitable solvent, preferably methanol or DMF, or purified by chromatographic methods, preferably by column chromatography (silica gel gradient 2-5% anhydrous, NH<sub>3</ sub> in MeOH/DCM). The compounds of the invention are multi-target monoamine ligands, in particular the dopamine D<sub>2</sub> and serotonin 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> receptors, for applications in the treatment of mental illnesses in particular schizophrenia, bipolar disorder and depression.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL438130A PL438130A1 (en) | 2021-06-11 | 2021-06-11 | Derivatives of 5-substituted-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, method of their preparation and their applicatione |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL438130A PL438130A1 (en) | 2021-06-11 | 2021-06-11 | Derivatives of 5-substituted-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, method of their preparation and their applicatione |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL438130A1 true PL438130A1 (en) | 2022-12-12 |
Family
ID=84441511
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL438130A PL438130A1 (en) | 2021-06-11 | 2021-06-11 | Derivatives of 5-substituted-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, method of their preparation and their applicatione |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL438130A1 (en) |
-
2021
- 2021-06-11 PL PL438130A patent/PL438130A1/en unknown
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