4-substituted 2,7-phthalazine compound, and preparation and usethereof

A technology of naphthyridines and compounds, which is applied to a class of 4-substituted 2,7-naphthyridine compounds and their preparation and application fields, and can solve problems such as harsh reaction conditions, low yields, and difficult availability of raw materials , to achieve the effect of convenient reaction, high yield and clean reaction

Inactive Publication Date: 2008-12-24
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in contrast to numerous naturally isolated or organically synthesized 1,5-, 1,6-, 1,7-, and 2,6-naphthyridines, currently reported 2,7-naphthyridines Quite limited, and its preparation method is very rare
In addition, there are many shortcomings in the method for the synthesis of this type of compound reported in the literature at present, as: the synthetic yield is low, and raw material is not easy to obtain, and reaction condition is harsh and is difficult to carry out derivatization etc.

Method used

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  • 4-substituted 2,7-phthalazine compound, and preparation and usethereof
  • 4-substituted 2,7-phthalazine compound, and preparation and usethereof
  • 4-substituted 2,7-phthalazine compound, and preparation and usethereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 14

[0054] Embodiment 14-phenyl-1-carbonyl-2, the preparation of 7-naphthyridine Ia

[0055] Step 1: 4-Methyl-3-cyano-2,6-dihydroxypyridine (compound 1)

[0056] Cyanoacetamide (1.0g, 11.9mmol) and ethyl acetoacetate (1.5ml, 11.9mmol) were placed in 15 ml of methanol, heated to dissolve it, and then 732.5 mg of potassium hydroxide was weighed and dissolved in 10 In the methyl alcohol of milliliter, the methanol solution of potassium hydroxide is added dropwise in the methanol solution of reactant with dropping funnel, stirs while adding dropwise, continues 15 minutes altogether, in the process of dropping, white solid will be produced, this During this time, a sufficient amount of methanol should be added to prevent the white solid from agglomerating, and then the reaction solution was stirred and refluxed for 8 hours. After the reaction, filter out the white solid, dissolve the obtained white solid in hot water, filter out the insoluble matter, acidify the filtrate with concentr...

Embodiment 2

[0069] Example 24-(4-methylphenyl)-1-carbonyl-2,7-naphthyridine Ib

[0070] According to the method of Example 1, in step 7, phenylboronic acid was replaced with 4-methylphenylboronic acid to obtain compound 4-(4-methylphenyl)-1-carbonyl-2,7-naphthyridine Ib.

[0071] White solid, yield 52%; 1 H NMR (CDCl 3 , 300MHz) δ2.436 (s, 3H, CH 3 ), 7.29-7.32(m, 4H, H-2', H-3', H-5', H-6'), 7.38(s, 1H, H-3), 7.47(d, J=5.4Hz , 1H, H-5), 8.72 (d, J=5.7Hz, 1H, H-6), 9.68 (s, 1H, H-8), 12.17 (brs, 1H, NH); MS (ESI) m / z 236[M + ](100); HRMS Calcd for C 15 h 12 N 2 O: 236.0950, found: 236.0943.

Embodiment 3

[0072] Example 34-(4-methoxyphenyl)-1-carbonyl-2,7-naphthyridine Ic

[0073]According to the method of Example 1, in step 7, phenylboronic acid is replaced with 4-methoxyphenylboronic acid to obtain compound 4-(4-methoxyphenyl)-1-carbonyl-2,7-naphthyridine Ic.

[0074] White solid, yield 50%; 1 HNMR (DMSO-d 6 , 300MHz) δ: 3.80(s, 3H,), 7.05(d, J=8.7Hz, 2H), 7.32(s, 1H), 7.35(d, J=8.7Hz, 2H), 7.37(d, J=8.7Hz, 2H), 7.37(d, J=8.7Hz, 2H), 6.3Hz, 1H), 8.69(d, J=5.4Hz, 1H), 9.38(s, 1H); 13 C NMR (75MHz, CDCl 3 )δ: 160.8(C-4'), 159.0(C-1), 151.2(C-8), 150.3(C-6), 142.3(C-10), 132.4(C-5), 130.8(C- 2', C-6'), 126.9(C-1'), 120.6(C-9), 117.5(C-3), 115.6(C-4), 114.4(C-3', C-5') , 55.3 (O-CH 3 ); MS(EI): m / z 252 [M + ](100); HRMS Cacld.for C 15 h 12 N 2 o 2 : 252.0899, found: 252.0897.

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Abstract

The invention relates to a 4-substituted 2,7-2,7-naphthyridine compound, a method for preparing the same and an application of the same in the preparation of mixed agonist or antagonist drugs or in prohibiting cytotoxicity, and resisting tumors and bacteria as a protease inhibitor. The compound has a structure shown in the genetic formula I or II, wherein R is a halogen, an alkyl, aryl or heteroaryl of a C1-C10 straight chain or side chain.

Description

technical field [0001] The present invention relates to 2,7-naphthyridine compounds with different substituents at the 4 positions and a preparation method thereof. The present invention also relates to the use of such compounds in the preparation of opioid receptor agonists or antagonists, or as protease inhibitors The purposes of the agent in inhibiting cytotoxicity, antitumor, antibacterial aspect. Background technique [0002] Many alkaloid natural product molecules contain naphthalene structural unit, which is a diazine heterocyclic aromatic system composed of two pyridines in parallel. According to the position of the two nitrogen atoms, it can be divided into 1,5-naphthyridine, 1,7-naphthyridine, 1,6-naphthyridine, 1,8-naphthyridine, 2,7-naphthyridine and 2,6- Naphthalene etc. This class of compounds has a wide range of biological activities and can be used in the diagnosis and treatment of various human diseases (including HIV virus infection). For example, Cimici...

Claims

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Application Information

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IPC IPC(8): C07D471/04A61K31/4375A61P35/00A61P25/00
Inventor 张翱丁春勇谢欣
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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