A small molecule fluorescent probe of phenylpiperazine α1-adrenoceptor and its application

A kind of epinephrine and fluorescent probe technology, applied in the field of medicine, can solve the problems of the research and development of biological and pharmacological properties lagging behind

Active Publication Date: 2011-12-14
SHANDONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] However, for α 1 - Adrenergic receptors, for which no fluorescent small molecule probes have been reported and only a few papers employ functional green fluorescent protein (GFP) fused macromolecular probes [(a) Awaji, T.; Hirasawa, A. .; Kataoka, M.; Shinoura, H.; Nakayama, Y.; Sugawara, T.; Izumi, S.; Tsujimoto, G. Real-time optical monitoring of ligand-mediated internalization of alphalb-adrenoceptor with green fluorescent protein. Mol .Endocrinol.1998, 12, 1099-1111; (b) Chalothorn, D.; McCune, D.F.; Edelmann, S.E.; Garcia-Cazarin, M.L.; of the alpha(1)-adrenoceptor subtypes. Mol. Pharmacol. 2002, 61, 1008-1016]
This makes the use of fluorescent small molecule probes for α 1 - Lag in the development of studies on the biological and pharmacological properties of adrenergic receptors

Method used

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  • A small molecule fluorescent probe of phenylpiperazine α1-adrenoceptor and its application
  • A small molecule fluorescent probe of phenylpiperazine α1-adrenoceptor and its application
  • A small molecule fluorescent probe of phenylpiperazine α1-adrenoceptor and its application

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0020] Example 1: N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-7-hydroxyl-1,2-benzopyrone-3-formamide ( Preparation of b1)

[0021] Preparation of intermediate a1-2:

[0022]

[0023] Preparation of intermediate (a1-1):

[0024] 100mL flask, add 2.76g 2,4-dihydroxybenzaldehyde and 25mL absolute ethanol, stir to make the solution clear, then add 3.84g diethyl malonate, while stirring, dissolve 0.17g morpholine and 66mg acetic acid In 10 mL of absolute ethanol, it was added to the above-mentioned reaction solution, refluxed and stirred for 9 h, the reaction solution was cooled in an ice bath, a large amount of precipitates precipitated, filtered, and dried to obtain 2.37 g of yellow needle-like solids with a yield of 50.64%.

[0025] Preparation of intermediate (a1-2):

[0026] Put 2.37g a1-1 into a 100mL flask, add 40mL 2M NaOH, stir at room temperature for 14h, add 2M HCl until the solution becomes acidic, and precipitate a large amount of precipitate, filter, and dry to...

example 2

[0042] Example 2: 1-(7-hydroxy-3-1,2-benzopyrone)-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl Preparation of}-1H-1,2,3-triazole-4-carboxamide (b2)

[0043] The synthetic route of b2:

[0044]

[0045] Preparation of intermediate a2-1:

[0046] Add 2.76g of 2,4-dihydroxybenzaldehyde, 2.34g of N-acetylglycine, 4.92g of anhydrous sodium acetate, and 85mL of acetic anhydride to a 250mL flask, reflux and stir for 5h, pour the reaction solution into ice water, and precipitate a large amount of precipitate. Filter and dry to obtain 2.03 g of a yellow solid with a yield of 38.9%.

[0047] Preparation of intermediate a2-2:

[0048] Put 0.3 g of a2-1 into a 250 mL flask, add 10 mL of concentrated hydrochloric acid and 5 mL of ethanol, stir at reflux for 1 hour, cool slightly, add ice water to the reaction solution, cool the reaction solution in an ice bath, slowly add 0.24 g of NaNO 2 , after stirring for 10-15 minutes, add 0.34gNaN 3 , stirred for 1 h, filtered, washed the pr...

example 3

[0057] Example Three: 2-(6-Hydroxy-3-oxo-3H-xanthen-9-yl)-5-{3-{2-[4-(2-methoxyphenyl)-1-piperazine The preparation of ethyl] ethyl} thiourea} benzoic acid (b3)

[0058] The synthetic route of b3:

[0059]

[0060] Add 136mg b, 1.4mL TEA and 15mL dichloromethane to a 50mL flask, stir to dissolve, and dissolve 97mgFITC in 4mL DMF under ice bath conditions, slowly drop in, rise to room temperature, stir in the dark for 3 days, spin out Solvent, in the form of oil, add ethyl acetate and methanol, precipitate a large amount of precipitate, filter, collect the precipitate, dissolve it with 2M NaOH, filter off the insoluble matter, add 2M HCl until the solution becomes acidic, precipitate a large amount of solid, filter, dry, and get yellowish brown Solid 80mg, yield 52.3%, mp: 188-190°C.

[0061] 1 HNMR (600MHz, DMSO-d 6 )δppm: 10.21 (s, 2H), 8.28 (s, 1H), 8.03 (s, 1H), 7.76 (s, 1H), 7.17 (d, 1H), 6.93-6.95 (m, 2H), 6.85-6.91 (m, 2H), 6.60-6.67(m, 2H), 6.55-6.59(m, 4H), 3.7...

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Abstract

The invention relates to a phenyl piperazine small-molecule fluorescent probe of an alpha1-adrenergic receptor and application thereof. General formulas of the small-molecule fluorescent probe are shown as a formula (I) and a formula (II) respectively, wherein R1 represents a single substituent or a multi-substituent of hydroxy, methyl, amino and halogen, and R2 and R3 represent various fluorophores. The fluorescent probe molecule can be used for marking the alpha-adrenergic receptor and be used as a tool drug for researching pharmacological and physiological characteristics of the alpha-adrenergic receptor. In addition, the preparation method of the compound has mild reaction conditions, cheap and easily available raw materials, and simple operations and post-treatments.

Description

technical field [0001] The present invention relates to phenylpiperazine derivatives and as α 1 - Small molecular fluorescent probes for adrenergic receptors and their application in the preparation of anti-prostate cancer drugs, belonging to the field of pharmaceutical technology. Background technique [0002] alpha 1 -Adrenergic receptors are important members of the G-protein coupled receptor family, which currently includes three subtypes: α 1A 、α 1B and alpha 1D [Zhong, H.; Minneman, K.P. Alphal-adrenoceptor subtypes. Eur J Pharmacol 1999, 375, 261-276]. alpha 1 -Adrenergic receptors found to be abundant in human benign prostatic hyperplasia and prostate cancer-associated cells [Shi, T.; Gaivin, R.J.; McCune, D.F.; Gupta, M.; Perez, D.M. Dominance of thealphal- adrenergic receptor and its sub cellular localization in human and TRAMP prostate cancer cell lines. J. Recept. Signal Transduct. Res. 2007, 27, 27-45]. Studies have shown that α 1A -Adrenergic receptors ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C09K11/06C07D311/16C07D405/04C07D311/82G01N21/64A61K31/496A61P35/00
CPCC09B57/02C09B11/08G01N33/582G01N33/9406G01N2333/726
Inventor 李敏勇杜吕佩李文华
Owner SHANDONG UNIV
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