Indole-3-carboxamide compounds and their applications

A formamide compound and formamide technology, applied in the field of medicine, can solve the problems of reduced ability to scavenge free radicals, etc., and achieve the effects of novel structure type, good application value and development and application prospects.

Active Publication Date: 2021-12-28
SHENYANG PHARMA UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Autopsy of AD patients found that the levels of 3-nitrotyrosine in brain tissue and cerebrospinal fluid were 5-8 times and 6 times higher than those of the corresponding control group, and the level of nitro-Mn-SOD in cerebrospinal fluid was increased. High, while the nitration of Mn-SOD in the mitochondrial protein can inactivate the enzyme, thereby reducing its ability to scavenge free radicals (Beal MF.Oxidatively modified proteins in aging and disease.Free Radic Biol Med.2002,32(9 ):797-803.)

Method used

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  • Indole-3-carboxamide compounds and their applications
  • Indole-3-carboxamide compounds and their applications
  • Indole-3-carboxamide compounds and their applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: N-benzyl-5-(2-diethylamino-2-oxoethoxy)-1,2-dimethyl-1H-indole-3-carboxamide (compound Z01) preparation

[0024] Step A: Preparation of ethyl 3-methylamino-2-butenoate

[0025] Put ethyl acetoacetate (15.01g, 0.12mol) in a 100mL eggplant-shaped bottle, slowly add 0.36mol of methylamine aqueous solution dropwise under stirring, continue to react for 3h at room temperature after the dropwise addition, let stand to separate layers, and wash the organic phase with water Once, dried over anhydrous sodium sulfate and filtered to obtain 15.08 g of light yellow liquid, yield: 91.4%.

[0026] Step B: Preparation of ethyl 1,2-dimethyl-5-hydroxy-1H-indole-3-carboxylate

[0027] Put p-benzoquinone (11.89g, 0.11mol) and 120mL of acetone in a 250mL eggplant-shaped flask, add 0.11mol of 3-methylamino-2-butenoic acid ethyl ester dropwise under stirring, and control the temperature at 30°C after the dropwise addition The reaction was continued for 2 hours, the solvent was ...

Embodiment 2

[0036] Embodiment 2: N-benzyl-5-(2-diethylamino-2-oxoethoxy)-2-methyl-1-ethyl-1H-indole-3-carboxamide (compound Z02 ) preparation

[0037] Referring to the preparation method of Example 1, 0.62 g of white solid was obtained, yield: 49.2%. M.p.: 105-106℃; IR: (KBr, cm -1 ):υ3434.3, 2925.2, 1661.7, 1617.5, 1530.2, 1478.3, 1347.7, 1259.2, 1189.2, 1139.2, 1082.9, 835.4, 756.0, 704.4; ESI-MS, m / z: calcd.421.24 (M + ); found 422.3([M+H] + ),444.3([M+Na] + ); 1 H NMR (400MHz, CDCl 3 ): δ7.43(d,J=2.3Hz,1H),7.36–7.27(m,5H),7.21(d,J=8.9Hz,1H),6.90(dd,J=8.9,2.4Hz,1H) ,4.71(d,J=5.7Hz,2H),4.65(s,2H),4.12(q,J=7.2Hz,2H),3.36(q,J=7.0Hz,4H),2.72(s,3H) , 1.33 (t, J = 7.2Hz, 3H), 1.17 (t, J = 7.1Hz, 3H), 1.11 (t, J = 7.1Hz, 3H).

Embodiment 3

[0038] Example 3: N-benzyl-5-(2-di-n-propylamino-2-oxoethoxy)-1,2-dimethyl-1H-indole-3-carboxamide (compound Z03) preparation

[0039]Referring to the preparation method of Example 1 Referring to the preparation method of Example 1, 1.08 g of white solid was obtained, yield: 82.4%. M.p.:123-125℃;IR:(KBr,cm -1 ):υ3349.0, 2964.9, 2871.1, 1656.2, 1484.3, 1382.6, 1270.8, 1190.0, 1143.3, 1084.6, 926.2, 839.0, 798.2, 741.2, 697.8; ESI-MS, m / z: calcd.435.25 (M + ); found 436.2([M+H] + ),458.3([M+Na] + ); 1 H NMR (400MHz, CDCl3): δ7.43 (d, J = 2.3Hz, 1H), 7.38–7.26 (m, 5H), 7.20 (d, J = 8.9Hz, 1H), 6.90 (dd, J = 8.9 ,2.4Hz,1H),4.71(d,J=5.7Hz,2H),4.67(s,2H),3.66(s,3H),3.26(q,J=7.0Hz,4H),2.72(s,2H ), 1.56–1.48 (m, 4H), 0.89 (t, J=7.4Hz, 3H), 0.84 (t, J=7.4Hz, 3H).

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Abstract

The invention belongs to the technical field of medicine, and relates to indole-3-carboxamide compounds and applications thereof. The general structural formula of described indole-3-carboxamide compound is as follows: wherein, R 1 , R 2 , R 3 , R as described in the claims and description. The indole-3-carboxamide compounds of the present invention and the pharmaceutically applicable acid addition salts of such compounds can be used as antioxidants for the preparation of drugs for the treatment or prevention of diseases related to protein oxidative damage, and protein oxidative damage The related diseases caused are Alzheimer's disease, Parkinson's disease, diabetes and chronic renal failure.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to indole-3-carboxamide compounds, their preparation method and their application as antioxidants. Background technique [0002] As a specific marker of oxidative damage in vivo, protein oxidation products mediated by free radicals have become one of the hotspots of free radical biology research in recent years. Proteins are prime targets for the action of free radicals and other oxidants, both inside and outside the cell. It is estimated that among macromolecules in cells, free radicals cleared by proteins account for 50% to 75% of the total active free radicals. Oxidative damage formation in proteins may be a highly sensitive indicator of oxidative damage in mammals due to the long half-lives of certain proteins that predispose them to the accumulation of oxidative damage. [0003] The level of intracellular oxidized proteins reflects the dynamic balance between the level of prot...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/42C07D405/12A61K31/404A61K31/454A61K31/5377A61P3/10A61P13/12A61P25/08A61P25/28A61P25/16A61P31/00
Inventor 胡春张兰王晶晶徐梅芹徐赫男谢倩孟广鹏
Owner SHENYANG PHARMA UNIVERSITY
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