PL430108A1 - 5-substituted-3-(1-arylmethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives, their preparation and application - Google Patents
5-substituted-3-(1-arylmethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives, their preparation and applicationInfo
- Publication number
- PL430108A1 PL430108A1 PL430108A PL43010819A PL430108A1 PL 430108 A1 PL430108 A1 PL 430108A1 PL 430108 A PL430108 A PL 430108A PL 43010819 A PL43010819 A PL 43010819A PL 430108 A1 PL430108 A1 PL 430108A1
- Authority
- PL
- Poland
- Prior art keywords
- substituted
- compounds
- arylmethyl
- isopropoxy
- hydrogen
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 12
- 150000001875 compounds Chemical class 0.000 abstract 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 abstract 3
- -1 furan-2-ylmethyl Chemical group 0.000 abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract 3
- 239000001257 hydrogen Substances 0.000 abstract 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 abstract 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 abstract 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 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
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 abstract 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 abstract 1
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical class O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 abstract 1
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 abstract 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 abstract 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 abstract 1
- 102000017911 HTR1A Human genes 0.000 abstract 1
- 101150015707 HTR1A gene Proteins 0.000 abstract 1
- 101150104779 HTR2A gene Proteins 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract 1
- 230000001430 anti-depressive effect Effects 0.000 abstract 1
- 230000000561 anti-psychotic effect Effects 0.000 abstract 1
- 239000002249 anxiolytic agent Substances 0.000 abstract 1
- 230000000949 anxiolytic effect Effects 0.000 abstract 1
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 239000003446 ligand Substances 0.000 abstract 1
- 239000002244 precipitate Substances 0.000 abstract 1
- 230000003414 procognitive effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- 208000020016 psychiatric disease Diseases 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 108020003175 receptors Proteins 0.000 abstract 1
- 102000005962 receptors Human genes 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-arylometylo-1,2,3,6-tetrahydropirydyn-4-ylo)-1H-indolu o wzorze ogólnym 1, gdzie R1 oznacza podstawnik furan-2-ylometylowy, natomiast R2 oznacza wodór, podstawnik etoksylowy lub izopropoksylowy, lub R1 oznacza podstawnik tiofen-2-ylometylowy natomiast podstawnik R2 oznacza wodór lub podstawnik C1-3alkoksylowy, lub R1 oznacza podstawnik benzylowy, natomiast R2 oznacza podstawnik izopropoksylowy, lub R1 oznacza podstawnik 3-metoksybenzylowy natomiast podstawnik R2 oznacza wodór lub podstawnik C1-3alkoksylowy, lub R1 oznacza podstawnik 4-metoksybenzylowy, natomiast podstawnik R2 oznacza podstawnik etoksylowy lub izopropoksylowy. Niniejsze zgłoszenie obejmuje także sposób otrzymywania powyższych związków. Związki będące przedmiotem wynalazku otrzymuje się w reakcji 5-podstawionych indoli z 1-arylometylopodstawionymi pochodnymi piperydyn-4-onu w metanolu w obecności wodorotlenku potasu. Reakcję prowadzi się przez 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. NH3 w MeOH/DCM). Zgłoszenie zawiera również zastosowanie przedmiotowych związków. Związki te są wielocelowymi ligandami monoamin, w szczególności receptora dopaminowego D2 oraz receptorów serotoninowych 5-HT1A i 5-HT2A, mogące ze względu na profil receptorowy wykazywać działanie przeciwpsychotyczne, przeciwlękowe, prokognitywne i przeciwdepresyjne korzystne w leczeniu chorób psychicznych, w szczególności schizofrenii, choroby afektywnej dwubiegunowej i depresji.The present invention relates to 5-substituted-3- (1-arylmethyl-1,2,3,6-tetrahydropyridin-4-yl) -1H-indole derivatives of the general formula 1, where R1 represents furan-2-ylmethyl and R2 is hydrogen, ethoxy or isopropoxy substituent, or R1 is thiophen-2-ylmethyl and R2 is hydrogen or C1-3alkoxy, or R1 is benzyl and R2 is isopropoxy or R1 is 3-methoxybenzyl and R2 is hydrogen or a C1-3alkoxy substituent, or R1 is 4-methoxybenzyl and R2 is ethoxy or isopropoxy. The present application also covers the preparation of the above compounds. The inventive compounds are prepared by reacting 5-substituted indoles with 1-arylmethyl substituted piperidin-4-one derivatives in methanol in the presence of potassium hydroxide. The reaction is carried out for 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 of the product after 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% anh NH3 in MeOH / DCM). The application also includes the use of the compounds in question. These compounds are multi-target ligands of monoamines, in particular the dopamine D2 receptor and serotonin 5-HT1A and 5-HT2A receptors, which, due to their receptor profile, may have antipsychotic, anxiolytic, procognitive and antidepressant effects, beneficial in the treatment of mental diseases, in particular schizophrenia, bipolar and depression.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL430108A PL241482B1 (en) | 2019-05-31 | 2019-05-31 | 5-substituted-3-(1-arylmethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives, their preparation and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL430108A PL241482B1 (en) | 2019-05-31 | 2019-05-31 | 5-substituted-3-(1-arylmethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives, their preparation and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL430108A1 true PL430108A1 (en) | 2020-12-14 |
| PL241482B1 PL241482B1 (en) | 2022-10-10 |
Family
ID=73727651
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL430108A PL241482B1 (en) | 2019-05-31 | 2019-05-31 | 5-substituted-3-(1-arylmethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives, their preparation and application |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL241482B1 (en) |
-
2019
- 2019-05-31 PL PL430108A patent/PL241482B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL241482B1 (en) | 2022-10-10 |
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