Benzothiazole and triazolediheterocycle-containing fused ring compound and application thereof

A benzothiazole and compound technology, which is applied in the field of bio-organic synthesis, can solve problems such as the inhibition of toxic and side effects of amnafite and mitonatamide, and achieve the effects of improving identification and embedding ability, improving biological activity, and expanding diversity

Inactive Publication Date: 2014-09-24
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Anticancer drugs based on naphthalimide, such as Amonafide, Mitonafide and UNBS5162, have also entered clinical trial

Method used

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  • Benzothiazole and triazolediheterocycle-containing fused ring compound and application thereof
  • Benzothiazole and triazolediheterocycle-containing fused ring compound and application thereof
  • Benzothiazole and triazolediheterocycle-containing fused ring compound and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] N-[2'-(4-((Benzothiazole-2-mercapto)methyl)-[1,2,3]-triazole)-ethyl]-4-hexahydropyridine-1,8-naphthalene Synthesis of imide (compound F4):

[0051] (1) Synthesis of 2-(2-alkyne-1-propylthio)benzo[d]thiazole (Intermediate 1)

[0052]

[0053] Weigh 3.02g (18mmol) of 2-mercaptobenzothiazole, dissolve it with 35mL of acetone, add 2.51mL (18mmol) of triethylamine, and the reaction solution is orange transparent liquid, add 1.41mL (18mmol) of propyl bromide alkyne, ultrasonically oscillated for 10 minutes, stopped the reaction, filtered to obtain a brown filtrate, and distilled the filtrate to remove the solvent under reduced pressure. 3.61 g of brown oily solid was obtained, yield: 98.0%.

[0054] (2) Synthesis of N-(2'-hydroxyethyl)-4-bromo-1,8-naphthalimide (intermediate 3)

[0055]

[0056] In a 50mL two-necked bottle, add 2.76g (10mmol) 4-bromo-1,8-naphthalene anhydride, add 0.7mL ethanolamine, 28mL absolute ethanol, heat up to reflux under magnetic stirring, r...

Embodiment 2

[0072] N-[2'-(4-((Benzothiazole-2-mercapto)methyl)-[1,2,3]-triazole)-ethyl]-4-morpholine-1,8-naphthoyl Synthesis of imine (compound F1):

[0073] Except that morpholine was used to replace hexahydropyridine in (3), other synthesis and experimental treatment methods were the same as in Example 1. Separation by silica gel column chromatography (column chromatography eluent is CH 2 Cl 2 :CH 3 OH=14:1), the target product F1 was obtained as a yellow-green solid with a yield of 79.8%. Melting point: 212.2-215.6°C.

[0074] 1 H NMR (400MHz, CDCl 3 )δ8.48(d, J=7.3Hz, 1H), 8.41(dd, J=13.7, 8.2Hz, 2H), 7.86(d, J=8.0Hz, 1H), 7.74(d, J=8.4Hz, 2H), 7.69–7.62(m, 1H), 7.41(t, J=7.2Hz, 1H), 7.31(d, J=8.0Hz, 1H), 7.18(d, J=8.1Hz, 1H), 4.72( t, J=6.0Hz, 2H), 4.70–4.48(m, 4H), 4.16–3.91(m, 4H), 3.37–3.11(m, 4H). 13 C NMR(101MHz,CDCl3)δ165.99,164.10,163.56,155.97,153.00,135.40,132.85,131.43,130.47,129.92,126.05,126.02,125.79,124.28,123.52,122.58,121.48,121.02,116.28,114.93,66.93,53.40 ...

Embodiment 3

[0077] N-[2'-(4-((Benzothiazole-2-mercapto)methyl)-[1,2,3]-triazole)-ethyl]-4-thiomorpholine-1,8- Synthesis of naphthalimide (compound F2):

[0078] Except replacing hexahydropyridine with thiomorpholine in (3), other synthesis and experimental treatment methods are the same as in Example 1. Separation by silica gel column chromatography (column chromatography eluent is CH 2 Cl 2 :CH 3 OH=6:1), the target product F2 was obtained as a yellow solid with a yield of 75.7%. Melting point: 206.5-208.1°C.

[0079] 1 H NMR (400MHz, CDCl 3)δ8.48(dd, J=7.3,1.0Hz,1H),8.42(d,J=8.1Hz,1H),8.34(dd,J=8.4,1.0Hz,1H),7.85(d,J=7.7 Hz, 1H), 7.75(d, J=7.9Hz, 2H), 7.66(dd, J=8.4, 7.4Hz, 1H), 7.41(t, J=7.2Hz, 1H), 7.30(t, J=7.6 Hz, 1H), 7.19(d, J=8.1Hz, 1H), 4.73(t, J=6.0Hz, 2H), 4.70–4.56(m, 4H), 3.51(s, 4H), 2.99(s, 4H ).

[0080] +ESI MS(M+H):C 28 h 24 N 6 o 2 S 3 , calculated value: 573.1123, measured value: 573.1181.

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Abstract

The invention relates to a benzothiazole and triazolediheterocycle-containing fused ring compound which has a structure of a general formula Y shown in the specification. According to the compound, cyclic amine with bioactivity is connected to the site 4 of naphthalimide, a structure that an imine nitrogen atom of naphthalimide is spaced from a triazole nitrogen atom connected with a side chain by two carbon atoms is kept, and molecules are introduced into sulfur-containing heterocyclic benzothiazole through linkage of triazole, so that the diversity of naphthalimide derivatives, the bioactivity of naphthalimide and the DNA identification and intercalation capability are improved; the compound has a relatively good inhibition effect on normal growth of tumor cells, with different tissue sources, of cervical cancers, liver cancers, breast cancers and the like.

Description

technical field [0001] The invention relates to a class of bis-heterocyclic naphthalimide compounds containing benzothiazole and triazole in the field of bioorganic synthesis, a preparation method and application thereof. Background technique [0002] Most of the molecules containing the naphthalimide parent structure are fluorescent and the compounds show a wide range of biological activities, such as anticancer drugs, antitrypanosomal agents, antiviral, local anesthetic, analgesic, serotonin 5-HT3 and 5-HT4 antibody antagonists, chemical sensors, etc. Anticancer drugs based on naphthalimide, such as Amonafide, Mitonafide and UNBS5162, have also entered clinical trials at different stages, but Amonafet and Mitonafide are due to their toxic and side effects. further research was inhibited. to 1973, reported for the first time that 3-nitronaphthoimide derivatives have antitumor activity, and then synthesized many naphthalimide compounds with antitumor activity by modifyin...

Claims

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Application Information

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IPC IPC(8): C07D417/14A61P35/00
CPCC07D417/14
Inventor 李晓莲尹方敏刘馨月张英利孟扬
Owner DALIAN UNIV OF TECH
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