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Thienothio compound and application thereof

A compound, thiophene technology, applied in the field of medicine, can solve problems such as reduced bioavailability and prolongation of cardiac QT interval

Inactive Publication Date: 2014-03-12
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Existing epidermal growth factor receptor tyrosine kinase inhibitors, such as gefitinib, erlotinib, lapatinib, etc., all have skin reactions such as diarrhea, rash, itching, and possible headache, heart attack, etc. Prolonged QT interval and decreased bioavailability, etc.

Method used

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  • Thienothio compound and application thereof
  • Thienothio compound and application thereof
  • Thienothio compound and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: 1-(7-bromo-1,4-dihydrothieno[3',2':5,6]thiapyro[4,3-c]pyrazole-3-carbonyl)-4- Preparation of (4-methylphenyl)piperazine (compound number 01)

[0026] Step A: Preparation of 5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-one

[0027] Add 4.64g (0.04mol) 2-mercaptothiophene and 80mL tetrahydrofuran into a 100mL round bottom flask, add 11mL triethylamine dropwise with stirring, then add 3.3mL acrylic acid, and heat to reflux for 12h. After the reaction was completed, tetrahydrofuran was distilled off. After cooling, 40 mL of ethyl acetate and 20 mL of water were added, the pH was adjusted to 2 with 18% hydrochloric acid, and the organic layer was collected. The aqueous layer was extracted with ethyl acetate, and the organic layers were combined and dried over anhydrous magnesium sulfate. After suction filtration, the filtrate was evaporated to remove the solvent, and a brown solid was precipitated after cooling. Petroleum ether was recrystallized to obtain a white ...

Embodiment 2

[0046] Example 2: 1-(7-bromo-1,4-dihydrothieno[3',2':5,6]thiapyrano[4,3-c]pyrazole-3-carbonyl)-4- Preparation of (diphenylmethyl)piperazine (compound number 02)

[0047] According to the method of Example 1, 1-(7-bromo-1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]pyrazole-3-carbonyl was obtained )-4-(diphenylmethyl)piperazine 0.77g, yield 35%. m.p.: 175-176℃; IR(KBr,cm -1 ):3420,2921,2851,1607,1451,1384,1262,1154,1027,997,877,831,705; 1 H-NMR (600MHz, CDCl 3 ):δ2.44(4H,m),3.79(4H,m),4.16(2H,s),4.25(1H,s),7.19(2H,d,J=8.4Hz),7.28(4H,dd, J=7.2Hz,8.4Hz),7.41(4H,d,J=7.2Hz); ESI-MS(m / z):551.2[M+H] + .

Embodiment 3

[0048] Example 3: N,N-diethyl-7-bromo-1,4-dihydrothieno[3',2':5,6]thiapyrano[4,3-c]pyrazole-3- Preparation of amides (compound number 03)

[0049] According to the method of Example 1, N,N-diethyl-7-bromo-1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]pyridine was prepared Azole-3-amide (Compound No. 03) 0.75 g, yield 50%. m.p.:147-148℃;IR(KBr,cm -1 ):3212,2958,2917,2849,1735,1583,1535,1508,1485,1461,1375,1215,1159,967,849; 1 H-NMR (600MHz, CDCl 3 ):δ1.25(6H,m),3.54(4H,m),4.12(2H,s),7.72(1H,s); ESI-MS(m / z):372.0,374.0[M+H] + .

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Abstract

The invention belongs to the technical field of medicines and relates to a thienothio compound and an application thereof. A thienothiapyran compound comprises derivatives and pharmaceutically applicable salt of the thienothiapyran compound, and has a structural formula; the thienothiapyran compound and the pharmaceutically applicable acid addition salt of the thienothiapyran compound can be combined with conventional drugs or are individually used as epidermal growth factor tyrosine kinase inhibitors for treating related diseases of epidermal growth factor receptor signaling dysregulation, such as small cell lung cancers, squama cancers, glandular cancers, large cell cancers, colorectal cancers, breast cancers, ovarian cancers, renal cell cancers and bronchial asthma.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a thienothia compound and its application as an epidermal growth factor receptor tyrosine kinase inhibitor, and a preparation method thereof. Background technique [0002] According to the degree of differentiation and morphological characteristics of cancer cells, lung cancer can be divided into non-small cell lung cancer and small cell lung cancer. Studies have found that there is a large number of dysregulation of epidermal growth factor signal transduction and overexpression of epidermal growth factor receptor tyrosine kinase in lung cancer patients. [0003] It is known that the epidermal growth factor receptor (EGFR), as a member of the receptor tyrosine kinase family, is a transmembrane glycoprotein composed of an extracellular epidermal growth factor binding region (containing 621 Amino acid residues), hydrophobic transmembrane domain (23 amino acid residues), intracellul...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/14A61K31/496A61K31/4162A61K31/5377A61K31/454A61P35/00A61P11/06
CPCC07D495/14
Inventor 胡春王欣金辄刘晓平黄二芳
Owner SHENYANG PHARMA UNIVERSITY