Amide compounds, compositions and applications thereof

A compound and solvate technology, which is applied in the field of amide compounds, compositions and their applications, can solve the problems of cognitive impairment, motor control, and limitation of wide clinical application

Inactive Publication Date: 2014-07-30
ADVINUS THERAPEUTICS PVT LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these agents also produce side effects, including cognitive impairment, motor control, which limit their wide clinical application

Method used

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  • Amide compounds, compositions and applications thereof
  • Amide compounds, compositions and applications thereof
  • Amide compounds, compositions and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 11

[0706] Example 1.1N-(5-chlorothiazol-2-yl)-4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]methylene]cyclohexyl Alkane carboxamide

[0707]

[0708] 4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-methylene]cyclohexanecarboxylic acid (intermediate 1A) (1.0g , 2.7 mmol) in DCM (20 mL) was added DMF (0.01 mL) followed by oxalyl chloride (0.5 mL, 5.3 mmol). After stirring at room temperature for 2 h, the volatiles were evaporated. The resulting residue was dissolved in DCM (5 mL) at 0 °C and a solution of 2-amino-5-chlorothiazole hydrochloride (Intermediate 2A) (680 mg, 4.0 mmol) in DCM (15 mL) was added. Triethylamine (1.1 mL, 8.0 mmol) was added thereto and stirred for 2 h. Water (30 mL) was added to quench the reaction. The organic layer was diluted with DCM (50 mL), separated, washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography to give 400 mg (34%) of the title compound as a solid.

[0709] 1...

Embodiment 12

[0713] Example 1.2: N-(3-pyridyl)-4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-methylene]cyclohexane Amide hydrochloride

[0714]

[0715] 4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-methylene]cyclohexanecarboxylic acid (300mg, 0.8mmol) in DCM at 0°C (50 mL) was added DMF (0.01 mL) followed by oxalyl chloride (0.2 mL, 1.6 mmol). Stir at room temperature for 2h and evaporate the volatiles. The resulting residue was dissolved in DCM (2 mL) at 0 °C and a stirred solution of 3-aminopyridine (Intermediate 2F) (75 mg, 0.8 mmol) in DCM (3 mL) was added. Triethylamine (0.1 mL, 0.9 mmol) was added thereto and stirred for 2 h. Water (10 mL) was added to quench the reaction. The organic layer was diluted with DCM (10 mL), separated, washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography. The resulting product was stirred with 4N HCl in dioxane (5 ml) for 1 h. Excess solvent was evaporated under redu...

Embodiment 21

[0717] Example 2.1: N-[4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]methylene]cyclohexyl]pyridine-3-carboxamide

[0718]

[0719] 4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]methylene]cyclohexylamine (Intermediate 3A) (200mg, 0.57mmol) at 0°C and a mixture of nicotinoyl chloride (Intermediate 4A) (150 mg, 0.86 mmol) in DCM (10 mL) was slowly added triethylamine (0.5 mL, 3.5 mmol). After stirring at room temperature for 2 h, the volatiles were evaporated under reduced pressure. The resulting residue was taken up in ethyl acetate (25 mL) and washed with anhydrous saturated sodium bicarbonate solution (20 mL), water (20 mL), brine (20 mL), dried over anhydrous sodium sulfate, filtered, concentrated and purified by preparative HPLC , thus giving 75 mg (30%) of N-[4-[[3-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]methylene]cyclohexyl]-pyridine -3-Carboxamide.

[0720] 1 H NMR (400MHz, CDCl 3 ): δ1.37(qd, J=11.0, 5.6Hz, 1H), 1.48(qd, J=11.3, 5.1Hz, 1H), 2.15-2.59(m, ...

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PUM

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Abstract

The present disclosure relates to substituted amide compounds that are inhibitors of Fatty Acid Amide Hydrolase (FAAH), their stereoisomers, tautomers, prodrugs, polymorphs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions containing them. These compounds are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of Fatty Acid Amide Hydrolase (FAAH), such as pain including acute and post operative pain, chronic pain, cancer pain, cancer chemotherapy induced pain, neuropathic pain, nociceptive pain, inflammatory pain, back pain, pain due to disease of various origin such as: diabetic neuropathy, neurotropic viral disease including human immunodeficient virus (HIV), herpes zoster such as post herpetic neuralgia; polyneuropathy, neurotoxicity, mechanical nerve injury, carpal tunnel syndrome, immunologic mechanisms like multiple sclerosis; sleep disorders, anxiety and depression disorders, inflammatory disorders, weight and eating disorders, Parkinson's disease, addiction, spasticity, hypertension or other disorders. The disclosure also relates to the process of preparation of the amide compounds. Formula (1). The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.

Description

technical field [0001] The present disclosure relates to substituted amides that are inhibitors of fatty acid amide hydrolase (FAAH), their stereoisomers, tautomers, prodrugs, polymorphs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The provided compounds, pharmaceutical compositions and methods are useful in the treatment, prevention, prevention, management or adjunctive treatment of all medical conditions associated with the inhibition of fatty acid amide hydrolase (FAAH). Background technique [0002] The endogenous cannabinoid system consists of two G protein-coupled receptors, CB1 and CB2; their endogenous ligands such as N-arachidonoyl ethanolamine (Anandamide, AEA) and 2 - Arachidylglycerol (2-AG); Enzyme composition involved in their biosynthesis and biodegradation (Fowler, C.J. et al., Clin.Pharmacol, 2006, 20, 549-562; Pacher, P., et al. Pharmacol.Rev., 2006, 58, 389-462). The magnitude and duration of fatty acid ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/60C07D241/14C07D401/12C07D413/12A61K31/33A61P25/00
CPCC07D213/75C07D213/82C07D401/12C07D401/14C07D409/12C07D413/12C07D417/12C07D471/04C07F9/6561A61K31/4439A61K31/444A61K31/497A61K31/675A61P25/00A61P25/04A61P25/16A61P25/28A61P43/00A61K45/06C07F9/65616
Inventor R·卡鲁尔D·布尼亚K·A·穆赫塔尔U·辛格A·哈扎尔S·帕蒂尔L·塔他让M·塔喀尔
Owner ADVINUS THERAPEUTICS PVT LTD
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