Unlock instant, AI-driven research and patent intelligence for your innovation.

1-naphthyl alkylpiperidine derivative

A kind of alkyl, alkylene technology, applied in the field of 1-naphthyl alkyl piperidine derivatives, can solve the problem of no disclosure and teaching, enhancing MCH receptor antagonism and the like

Inactive Publication Date: 2009-12-02
TAISHO PHARMACEUTICAL CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no disclosure and teaching in these documents: by introducing substituents on the naphthalene skeleton, thereby enhancing the MCH receptor antagonism

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 1-naphthyl alkylpiperidine derivative
  • 1-naphthyl alkylpiperidine derivative
  • 1-naphthyl alkylpiperidine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0474] Example 1: 3-methoxy-N-[1-({7-[(2-methoxyethoxy)methyl]-2-naphthyl}methyl)piperidin-4-yl]benzene Synthesis of Formamide Hydrochloride

[0475] Step 1-1: Under nitrogen atmosphere, under ice cooling, to LiAlH 4 To a THF (1.25 L) suspension of (81.6 g) was added a THF (2.50 L) solution of dimethyl naphthalene-2,7-dicarboxylate (250 g), and the temperature was raised to room temperature. After stirring for 1 hour, ice cooling was performed again, and Na 2 SO 4 10H 2 O, stirred at room temperature for 15 minutes. The reaction solution was filtered through celite, washed with heated THF (12.0 L), and the filtrate was concentrated under reduced pressure. To the resulting bold was added CHCl 3 (1.00 L) was stirred for 10 minutes, and the solid was collected by filtration to obtain naphthalene-2,7-diyldimethanol (151 g, colorless solid).

[0476] 1 H NMR (200MHz, DMSO-d 6 , δ): 4.66(d, J=5.7Hz, 4H), 5.31(t, J=5.7Hz, 2H), 7.42(dd, J=8.6, 1.5Hz, 2H), 7.73-7.88(m, 4H) ; ...

Embodiment 2

[0487] Example 2: 3-methoxy-N-[1-({7-[(2-methoxyethoxy)methyl]-2-naphthyl}methyl)piperidin-4-yl]benzene Synthesis of formamide hydrobromide

[0488] To an EtOAc (10.0 mL) suspension of the compound (1.00 g) obtained in Step 1-5 was added 48% HBr aqueous solution (730 mg), followed by stirring at room temperature for 2.5 hours. The resulting solid was collected by filtration to obtain the title compound (1.09 g, colorless solid).

[0489] 1 H NMR (600MHz, CDCl 3, δ): 2.18-2.24(m, 2H), 2.53-2.63(m, 2H), 2.93-3.01(m, 2H), 3.43(s, 3H), 3.58-3.64(m, 4H), 3.68-3.71 (m, 2H), 3.84(s, 3H), 4.26-4.34(m, 1H), 4.37(d, J=5.0Hz, 2H), 4.76(s, 2H), 6.59(d, J=8.3Hz, 1H), 7.02-7.05(m, 1H), 7.28-7.33(m, 3H), 7.59-7.62(m, 1H), 7.82(dd, J=8.3, 1.8Hz, 1H), 7.87-7.90(m, 2H), 7.94(d, J=8.3Hz, 1H), 8.10(s, 1H), 11.62(brs, 1H); ESI / APCI MS m / z 463, [M(free)+H] + .

Embodiment 3

[0490] Example 3: Synthesis of 7-({4-[(3-methoxybenzoyl)amino]piperidin-1-yl}methyl)-2-naphthoic acid methyl ester

[0491] Step 3-1: NaBH was added to a solution of dimethyl naphthalene-2,7-dicarboxylate (100 g) in THF (1.60 L) under a nitrogen atmosphere 4 (30.9 g), then heated to 60°C. MeOH was added dropwise, heated to reflux for 6 hours, and further stirred at room temperature for 12 hours. Under ice-cooling, concentrated hydrochloric acid (70.0 mL) was added dropwise, stirred for 30 minutes, the resulting solid was filtered through celite, and the filtrate was concentrated under reduced pressure. To the residue was added EtOAc (2.00 L) and CHCl 3 (500 mL), and the resulting solid was filtered. with H 2 O washed the filtrate with MgSO 4 After drying, it was concentrated under reduced pressure. To the resulting residue was added CHCl 3 (1.30 L), and after stirring at room temperature for 12 hours, the solid was filtered. The filtrate was concentrated under reduced ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Disclosed is a pharmaceutical composition comprising a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient, which has an antagonistic activity on a melanin-concentrating hormone receptor. The pharmaceutical composition is useful, due to its antagonistic activity on a MCH receptor, for the prevention or treatment of a disease such as depression, anxiety disorder (e.g., generalized anxiety disorder, post traumatic stress disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder), attention deficit disorder, mania, manic-depressive disorder, schizophrenia, mood disorder, stress, sleep disorder, attack, memory dysfunction, cognitive impairment, dementia, amnesia, delirium, mental deterioration, obesity, eating disorder, appetite disorder, hyperphagia, bulimia, cibophobia, diabetes, a cardiovascular disease, hypertension, dyslipidemia, cardiac infarction, movement disorder (e.g., Parkinson's disease, epilepsy, convulsion, tremor), drug abuse disorder and drug addiction.

Description

technical field [0001] The present invention relates to a compound with melanin-concentrating hormone receptor antagonism and a pharmaceutically acceptable salt thereof. Background technique [0002] Depression and anxiety disorders constitute major psychiatric disorders, and the prevalence of depression and anxiety disorders has been increasing in recent years. So far, as antidepressants, tricyclic antidepressant (TCA), selective serotonin reuptake inhibitor (SSRI), serotonin- Norepinephrine reuptake inhibitor (serotonin and noradrenaline reuptake inhibitor: SNRI) and the like. Use of gamma-aminobutyric acid (GABA)-based benzodiazepines as anxiolytics Class drugs, in recent years, SSRI and SNRI for panic disorder and obsessive-compulsive disorder and other benzodiazepines Anxiety disorders where similar drugs do not work have also shown an effect, making it the first choice drug for anxiety disorders. But the problem is that there are patients with treatment-resistant...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/58A61K31/4468A61K31/453A61K31/454A61K31/4545A61K31/496A61K31/506A61K31/5377A61P3/04A61P3/06A61P3/10A61P9/10A61P9/12A61P25/08A61P25/14A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P25/36A61P43/00C07D401/10C07D401/12C07D405/10C07D405/12
Inventor 关口喜功鹿沼幸祐坂上一成林真知柏修平表寺克纪
Owner TAISHO PHARMACEUTICAL CO LTD