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2-(2,2-diaryl vinyl) cyclamine derivative and preparation method thereof

A technology of diarylethene and its derivatives, which is applied in the fields of active ingredients of heterocyclic compounds, drug combinations, and pharmaceutical formulations, etc.

Inactive Publication Date: 2019-09-17
TAIZHOU GUOKEHUAWU BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Only GB765853 reported in 1951 that a few (2,2-diphenylvinyl)-piperidine derivatives (as shown in III) can be used as antispasmodics for the treatment of gastrointestinal tract, genitourinary tract, bronchial tract, etc. spasticity or smooth muscle contraction, but in the structure of the type III compound, no substituents are claimed on the phenyl and pyridine groups, and the special function of the special substituent is indicated

Method used

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  • 2-(2,2-diaryl vinyl) cyclamine derivative and preparation method thereof
  • 2-(2,2-diaryl vinyl) cyclamine derivative and preparation method thereof
  • 2-(2,2-diaryl vinyl) cyclamine derivative and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0123] Synthesis of 2-[(E)-2-(2-hydroxy-phenyl)-2-phenylethenyl]-N-methylpiperidine (I-1)

[0124]

[0125] 1.1 Synthesis of (2-methoxymethoxy-phenyl)(phenyl)-methanone

[0126] Dissolve (2-hydroxy-phenyl)(phenyl)-methanone (1.98g, 10mmol) in dichloromethane (50ml), add diisopropylethylamine (30mmol), stir at room temperature, add methyl chloride methyl ether (20 mmol). Heated to reflux for 12 hours, monitored by TLC, after the reaction was completed. The reaction solution was cooled to room temperature, the solvent was removed by rotary evaporation, and purified by silica column chromatography to obtain 2.2 g of a brown oily product of (2-methoxymethoxy-phenyl) (phenyl)-methanone (yield 91 %). 1 H NMR (400MHz, CDCl 3 ), δ: 7.84-7.82(m, 2H), 7.58-7.54(m, 1H), 7.47-7.42(m, 3H), 7.37(q, J=12.0Hz, 1H), 7.21(d, J=8.0 Hz, 1H), 7.12-7.09(m, 1H), 5.05(s, 2H), 3.29(s, 3H).

[0127] 1.2 Synthesis of 3-(2-methoxymethoxy-phenyl)-3-(phenyl)-methyl acrylate

[0128] At room tempera...

Embodiment 2

[0140] Synthesis of 2-[2,2-bis(2-hydroxy-phenyl)-vinyl]-N-methylpiperidine (I-2)

[0141]

[0142] 2.1 Synthesis of bis(2-methoxymethoxy-phenyl)-methanone

[0143] According to the steps described in 1.1 in Example 1, using bis(2-hydroxyl-phenyl)-methanone as raw material, and the consumption of DIEA and chloromethyl methyl ether is doubled, bis(2-methoxymethoxy A brown oily product of phenyl-phenyl)-methanone in 92% yield. 1 H NMR (400MHz, CDCl 3 ), δ: 7.54-7.52 (m, 2H), 7.43-7.39 (m, 2H), 7.12-7.04 (m, 4H), 4.98 (s, 4H), 3.26 (s, 6H).

[0144] 2.2 Synthesis of 3,3-bis(2-methoxymethoxy-phenyl)-methyl acrylate

[0145] According to the steps described in 1.2 in Example 1, using bis(2-methoxymethoxy-phenyl)-methanone as raw material, 3,3-bis(2-methoxymethoxy-phenyl)- Brown oily product of methyl acrylate, 81% yield. 1 H NMR (400MHz, CDCl 3 ), δ: 7.29-7.22(m,2H),7.15(d,J=8.0Hz,1H),7.11-7.04(m,3H),6.98-6.92(m,2H),6.36(s,1H), 5.05(s,2H), 4.99(s,2H), 3.60(s,3H), 3.28(s,3H...

Embodiment 3

[0157] 2-[(E)-2-(2-Hydroxy-5-methyl-phenyl)-2-phenylvinyl]-N-methylpiperidine (I-3, and its chiral monomer I- 3-1 and I-3-2) synthesis:

[0158]

[0159] 3.1 Synthesis of (2-hydroxy-5-methyl-phenyl)(phenyl)-methanone

[0160] Weigh p-cresol (2.16g, 20mmol) and anhydrous AlCl 3 (3.2g, 24mmol), put into a 250ml round bottom flask and heat to 120°C. After 20 minutes, add benzoyl chloride (3.37g, 24mmol) in batches as a raw material, control the temperature at 100-140°C and stir the reaction, monitor by TLC. After the reaction is completed, pour 50ml of ice water into the bottle, and then add 10ml of concentrated hydrochloric acid . The suspension was stirred for 10 minutes, extracted with dichloromethane (3x50ml), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and purified by silica column chromatography to obtain a yellow solid product (2-hydroxyl-5 -Methyl-phenyl)(phenyl)-methanone 3.4 g (80% yield). (Reference...

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Abstract

The invention provides a 2-(2,2-diaryl vinyl) cyclamine derivative and a preparation method thereof. Aryl substituent groups have hydroxy or hydroxy derivative functional groups at ortho-positions of vinyl groups. Biological activity tests show that the compound has activity of antagonistic muscarinic receptors (M receptors); ortho hydroxyl can obviously enhance the antagonistic activity; the compound can be used as a medicine active ingredient and is used for treating diseases relevant to the M receptor.

Description

technical field [0001] The invention relates to a novel diaryl vinyl cyclic amine derivative, in particular to a diaryl vinyl cyclic amine derivative and a preparation method thereof. Background technique [0002] Diaryl allylamine derivatives are an important class of intermediates in drug synthesis, and they also have various pharmacological activities. Brit. J. Pharmacol. 1951, 6, 560-571 reported that a series of compounds with diaryl allylamine structure (as shown in structure II) had obvious antihistamine, antispasmodic and anesthetic activities. Acta Pharmacol.etotoxicol.1951,7,51-64 found a compound with similar structure 1,1-diphenyl-3-dimethylamino-butene, which has anticholinergic effect and exhibits obvious antispasmodic activity , also has mild analgesic activity. Subsequently, R.F.MAISEY etc. also reported a class of diphenylallylamine derivatives (GB 1134715, GB 1135926 and J.Med.Chem., 1971,14 (2), 161-164) in a series of work, They all have significant an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/22C07D207/08C07D409/10A61K31/4535A61K31/40A61K31/445A61P11/06A61P11/00A61P29/00A61P11/02A61P37/08A61P31/00A61P25/16A61P13/00
CPCC07D207/08C07D211/22C07D409/10
Inventor 梁鑫淼赵耀鹏刘艳芳王纪霞王长健王志伟杜娜娜张秀莉郭志谋王超然
Owner TAIZHOU GUOKEHUAWU BIOMEDICAL TECH CO LTD