PL245768B1 - Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie - Google Patents

Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie Download PDF

Info

Publication number: PL245768B1
Authority: PL; Poland
Prior art keywords: benzo; dihydro; chloro; sub; reaction
Prior art date: 2022-12-01

Application number

PL443018A

Other languages

English (en)

Polish (pl)

Other versions

PL443018A1 (pl

Inventor

Agnieszka Anna Kaczor

Tomasz M. Wróbel

Angelika Grudzińska

Agata Zięba

Piotr Stępnicki

Dariusz Matosiuk

María De Los Ángeles Castro Pérez

Pérez María De Los Ángeles Castro

Original Assignee

Univ Medyczny W Lublinie

Univ Santiago Compostela

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2022-12-01

Filing date

2022-12-01

Publication date

2024-10-07

2022-12-01 Application filed by Univ Medyczny W Lublinie, Univ Santiago Compostela filed Critical Univ Medyczny W Lublinie

2022-12-01 Priority to PL443018A priority Critical patent/PL245768B1/pl

2023-11-23 Priority to ES202330969A priority patent/ES2964230B2/es

2024-06-03 Publication of PL443018A1 publication Critical patent/PL443018A1/pl

2024-10-07 Publication of PL245768B1 publication Critical patent/PL245768B1/pl

Links

HYQZZYOFKWMTPW-UHFFFAOYSA-N n-[(6-chloro-3,4-dihydro-2h-1,5-benzodioxepin-8-yl)methyl]-2-(6-fluoro-1h-indol-3-yl)ethanamine Chemical class O1CCCOC2=CC(CNCCC=3C4=CC=C(C=C4NC=3)F)=CC(Cl)=C21 HYQZZYOFKWMTPW-UHFFFAOYSA-N 0.000 title claims abstract description 8
238000000034 method Methods 0.000 title claims description 7
238000002360 preparation method Methods 0.000 title description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 36
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 claims abstract description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 18
238000006243 chemical reaction Methods 0.000 claims abstract description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 15
238000002425 crystallisation Methods 0.000 claims abstract description 15
230000008025 crystallization Effects 0.000 claims abstract description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 7
QRAWNNQNLQPNIZ-UHFFFAOYSA-N 2-(7-fluoro-1h-indol-3-yl)ethanamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1F QRAWNNQNLQPNIZ-UHFFFAOYSA-N 0.000 claims abstract description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 6
239000000203 mixture Substances 0.000 claims abstract description 6
229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 6
239000012279 sodium borohydride Substances 0.000 claims abstract description 6
229910052938 sodium sulfate Inorganic materials 0.000 claims abstract description 6
235000011152 sodium sulphate Nutrition 0.000 claims abstract description 6
QTNVDKAISCZLHR-UHFFFAOYSA-N 2-(4-fluoro-1h-indol-3-yl)ethanamine Chemical compound C1=CC(F)=C2C(CCN)=CNC2=C1 QTNVDKAISCZLHR-UHFFFAOYSA-N 0.000 claims abstract description 5
ZKIORVIXEWIOGB-UHFFFAOYSA-N 2-(5-fluoro-1h-indol-3-yl)ethanamine Chemical compound C1=C(F)C=C2C(CCN)=CNC2=C1 ZKIORVIXEWIOGB-UHFFFAOYSA-N 0.000 claims abstract description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 5
102000005962 receptors Human genes 0.000 claims abstract description 5
108020003175 receptors Proteins 0.000 claims abstract description 5
239000003446 ligand Substances 0.000 claims abstract description 4
208000020016 psychiatric disease Diseases 0.000 claims abstract description 4
BQTOKMYKZPCPRW-UHFFFAOYSA-N 2-(6-fluoro-1h-indol-3-yl)ethanamine Chemical compound FC1=CC=C2C(CCN)=CNC2=C1 BQTOKMYKZPCPRW-UHFFFAOYSA-N 0.000 claims abstract description 3
PFMDPBFEHLDZOY-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-1,5-benzodioxepine-8-carbaldehyde Chemical compound O1CCCOC2=C1C=C(C=O)C=C2Cl PFMDPBFEHLDZOY-UHFFFAOYSA-N 0.000 claims abstract description 3
239000001257 hydrogen Chemical group 0.000 claims description 6
229910052739 hydrogen Chemical group 0.000 claims description 6
102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 claims description 5
101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
230000008020 evaporation Effects 0.000 claims description 5
238000001704 evaporation Methods 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
239000000047 product Substances 0.000 claims description 4
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 claims description 3
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 claims description 3
CPCIGYYORXNALX-UHFFFAOYSA-N n-fluoro-2-(1h-indol-3-yl)ethanamine Chemical compound C1=CC=C2C(CCNF)=CNC2=C1 CPCIGYYORXNALX-UHFFFAOYSA-N 0.000 claims description 3
239000012153 distilled water Substances 0.000 claims description 2
239000011541 reaction mixture Substances 0.000 claims description 2
150000003839 salts Chemical class 0.000 claims description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
239000007795 chemical reaction product Substances 0.000 claims 2
150000002431 hydrogen Chemical group 0.000 claims 2
229910052786 argon Inorganic materials 0.000 claims 1
238000001816 cooling Methods 0.000 claims 1
150000003840 hydrochlorides Chemical class 0.000 claims 1
239000011261 inert gas Substances 0.000 claims 1
239000002798 polar solvent Substances 0.000 claims 1
239000000460 chlorine Substances 0.000 abstract description 11
150000001875 compounds Chemical class 0.000 abstract description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 8
230000001430 anti-depressive effect Effects 0.000 abstract description 3
239000002249 anxiolytic agent Substances 0.000 abstract description 3
230000009286 beneficial effect Effects 0.000 abstract description 3
229910052801 chlorine Inorganic materials 0.000 abstract description 3
229910052731 fluorine Inorganic materials 0.000 abstract description 3
239000011737 fluorine Substances 0.000 abstract description 3
230000003414 procognitive effect Effects 0.000 abstract description 3
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 abstract description 2
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 abstract description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 1
230000000049 anti-anxiety effect Effects 0.000 abstract 1
238000000605 extraction Methods 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
238000005481 NMR spectroscopy Methods 0.000 description 17
239000000126 substance Substances 0.000 description 5
230000000144 pharmacologic effect Effects 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
-1 N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)methyl)-2-(1H-indol-3-yl)ethan-1-amine Chemical compound 0.000 description 3
239000003814 drug Substances 0.000 description 3
230000003595 spectral effect Effects 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 2
230000000949 anxiolytic effect Effects 0.000 description 2
230000008499 blood brain barrier function Effects 0.000 description 2
210000001218 blood-brain barrier Anatomy 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
229940079593 drug Drugs 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
210000000653 nervous system Anatomy 0.000 description 2
230000004770 neurodegeneration Effects 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
230000035699 permeability Effects 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
101150104779 HTR2A gene Proteins 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
108010024941 iodothyronine deiodinase type II Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

PL443018A 2022-12-01 2022-12-01 Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie PL245768B1 (pl)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
PL443018A PL245768B1 (pl)	2022-12-01	2022-12-01	Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie
ES202330969A ES2964230B2 (es)	2022-12-01	2023-11-23	Derivados N-((9-cloro-3,4-dihidro-2H-benzo[b][1,4]dioxepin-7-il)metil)-2-(6-fluoro-1H-indol-3-il)etano-1-amina, su modo de obtencion y su utilizacion

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PL443018A PL245768B1 (pl)	2022-12-01	2022-12-01	Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie

Publications (2)

Publication Number	Publication Date
PL443018A1 PL443018A1 (pl)	2024-06-03
PL245768B1 true PL245768B1 (pl)	2024-10-07

Family

ID=90526820

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PL443018A PL245768B1 (pl)	2022-12-01	2022-12-01	Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie

Country Status (2)

Country	Link
ES (1)	ES2964230B2 (es)
PL (1)	PL245768B1 (es)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MXPA05006433A (es) *	2002-12-20	2005-08-19	Merck Patent Gmbh	Benzodioxepinas sustituidas.

2022
- 2022-12-01 PL PL443018A patent/PL245768B1/pl unknown
2023
- 2023-11-23 ES ES202330969A patent/ES2964230B2/es active Active

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KACZOR ET AL.: "Chem. Med. Chem. 2016, 11, 7, 718-729, 18.03.2016", STRUCTURE-BASED VIRTUAL SCREENING FOR DOPAMINE D2 RECEPTOR LIGANDS AS POTENTIAL ANTIPSYCHOTICS *
STEPHEN M. STAHL: "CNS Spectrums 2017, 22, 5, 375-385, 2.10.2017", DRUGS FOR PSYCHOSIS AND MOOD: UNIQUE ACTIONS AT D3, D2, AND D1 DOPAMINE RECEPTOR SUBTYPES *

Also Published As

Publication number	Publication date
ES2964230B2 (es)	2024-11-04
ES2964230A1 (es)	2024-04-04
PL443018A1 (pl)	2024-06-03

Publication	Publication Date	Title
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US20100286189A1 (en)	2010-11-11	(aza)indole derivative substituted in position 5, pharmaceutical composition comprising it, intermediate compounds and preparation process therefor
US6699864B2 (en)	2004-03-02	Substituted phenyl-piperazine derivatives, their preparation and use
KR20020067589A (ko)	2002-08-22	페닐피페라지닐 유도체
JPS61155358A (ja)	1986-07-15	ジアリール酪酸誘導体
CZ323794A3 (en)	1995-05-17	N-substituted azabicycloheptane derivatives, process of their preparation and their use
JP2740250B2 (ja)	1998-04-15	ヘテラ―脂肪族カルボクサミド誘導体、その製造方法、該化合物の中間体および該化合物を含有するロイコトリエン拮抗作用を有する薬学的組成物
EP0290145B1 (en)	1994-10-26	Aliphatic carboxamides
IL150366A (en)	2008-06-05	4-phenyl-1-piperazinyl,-piperidinyl and -tetrahydropyridyl derivatives
FR2751649A1 (fr)	1998-01-30	Nouveaux derives de benzimidazole, de benzoxazole et de benzothiazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
PL245768B1 (pl)	2024-10-07	Pochodne N-((9-chloro-3,4-dihydro-2H-benzo[b][1,4]dioksepin-7-ylo)metylo)-2-(6-fluoro-1H-indol-3-ylo)etano-1-aminy, sposób ich wytwarzania i zastosowanie
JPH06287190A (ja)	1994-10-11	新規な３−アミノクロマンスピロ化合物、それらの製造法およびそれらを含む薬学組成物
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PL241482B1 (pl)	2022-10-10	Pochodne 5-podstawione-3-(1-arylometylo-1,2,3,6-tetrahydropirydyn- 4-ylo)-1H-indolu, sposób ich wytwarzania