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A compound capable of inhibiting IDO, its preparation method and its use

一种化合物、用途的技术，应用在医药领域，能够解决未找到很好IDO抑制剂等问题，达到强抑制活性、好应用前景的效果

Active Publication Date: 2019-07-16
SHANGHAI JOYU PHARMATECH LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] IDO inhibitors as drugs have good application prospects in the pharmaceutical industry, but currently no good IDO inhibitors have been found as marketed drugs. In order to achieve better cancer treatment effects and better meet market demand, we hope to develop A new generation of selective IDO inhibitor with high efficiency and low toxicity

Method used

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  • A compound capable of inhibiting IDO, its preparation method and its use
  • A compound capable of inhibiting IDO, its preparation method and its use
  • A compound capable of inhibiting IDO, its preparation method and its use

Examples

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preparation example Construction

[0031] The preparation method of the compound represented by general formula (I) of the present invention or its salt, comprises the following steps:

[0032]

[0033]Under acidic conditions, the compound of general formula (Ia) is oxidized to the compound of general formula (Ib); the compound of general formula (Ib) reacts with the compound of general formula (Ic) under alkaline conditions to obtain the compound of general formula (Id); The compound of formula (Id) forms a ring under heating and basic conditions, and the base under this condition is preferably N, N'-carbonyldiimidazole to obtain a compound of general formula (Ie); the compound of general formula (Ie) after ring formation is Remove the protecting group on the amino under the condition, obtain general formula (If) compound or its salt; ) compound, the preferred tert-butanol solution of the alcoholic solution; the compound of general formula (Ig) removes the protecting group on the amino group under acidic co...

Embodiment 1

[0046] trans-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-((4-((sulfamoylamino)methyl)cyclohexyl)amino)-1,2,5-oxadiazole-3-carboximidamide, the compound The preparation of 1, wherein the structural formula of compound 1 is as follows:

[0047]

[0048] The first step, prepare compound lb:

[0049] The raw material compound la (500mg, 1.46mmol, prepared by referring to the method disclosed in P53 Example3 stepA in the patent application "WO2010005958") was added to 7mL of trifluoroacetic acid, then 6mL of hydrogen peroxide (30%) was added, and the reaction was carried out at 45°C for 20 hours . After the reaction, quench the reaction by adding saturated sodium sulfite solution, extract with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure, and purify the resulting residue by silica gel column chromatography with eluent system B Compound lb (410 mg, yellow oil) was obtained with a yield of 7...

Embodiment 2

[0065] trans-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-((4-(2-(sulfamoylamino)ethyl)cyclohexyl)amino)-1,2,5-oxadiazole-3-carboximidamide, That is the preparation of compound 2, wherein the structural formula of compound 2 is as follows:

[0066]

[0067] Using the synthetic method of Example 1, the second step raw material compound 1c is replaced by (commercially available) to obtain compound 2 (73 mg, white solid), with a yield of 45%. MS m / z(ESI):521.4[M+1] + , 1 HNMR(400MHz,DMSO-d6)δ11.52(s,1H),8.87(s,1H),7.09-7.27(m,3H),6.76-6.79(m,1H),6.67(s,2H),6.21 (t,1H), 2.41(m,1H), 1.20-1.83(m,11H), 3.55(d,2H).

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PUM

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Abstract

The invention discloses a compound capable of inhibiting IDO, its preparation method and its application. Its general structural formula is as follows: in, selected from a cis isomer, a trans isomer or a mixture of cis and trans isomers; R 1 and R 2 each independently selected from any one of hydrogen atom, halogen, alkyl, alkoxy or haloalkyl; R 3 Any one selected from cyclopentyl, cyclohexyl, piperazinyl, piperidinyl, R 3 The substitution positions are 1, 2, 1, 3 or 1, 4; m and n are integers of 0-5 respectively. The compound capable of inhibiting IDO provided by the present invention has strong inhibitory activity on IDO, and can be used to prepare IDO inhibitors to prevent and / or treat diseases with pathological characteristics of IDO-mediated tryptophan metabolic pathway, and has Very good application prospects.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a compound capable of inhibiting IDO, its preparation method and its application in medicine, and is used for treating diseases with pathological characteristics of IDO-mediated tryptophan metabolic pathway, and the diseases include Cancer, Alzheimer's disease, autoimmune diseases, depression, anxiety, cataracts, psychological disorders, AIDS, etc. Background technique [0002] Cancer is one of the major diseases that seriously endanger human life, and more than half of it occurs in developing countries. The overall incidence of cancer in my country is on the rise, and the incidence is increasing at an average annual rate of 3%-5%. It is estimated that by 2020, 4 million people in my country will develop cancer and 3 million people will die of cancer. The main reasons are: aging globalization, urbanization, industrialization and changes in living habits. In the Chinese hospital drug market...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D271/08A61K31/4245A61P35/00A61P35/02A61P37/02A61P25/28A61P25/22A61P25/24A61P25/00A61P31/18A61P27/12
CPCC07D271/08C07D271/04
Inventor 钟燕曹西蓉王永临
Owner SHANGHAI JOYU PHARMATECH LTD
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