Naphthlamide derivative used as protein kinase inhibitor and histone deacetylase inhibitor and preparation method of naphthlamide derivative

A technology of protein kinase inhibitor and sirtuin, which is applied in the field of preparation of naphthylamide derivatives, can solve the problems of high price, harsh reaction conditions, and low yield

CN102603627AInactive Publication Date: 2012-07-25福建太平洋制药有限公司
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2012-07-25
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a naphthlamide derivative used as a protein kinase inhibitor and a histone deacetylase inhibitor. The structure of the naphthlamide derivative is as shown as a formula I, wherein a position 7 is provided with substituent groups R which include F, Cl, Br, I, OCH3 and other substituent groups as shown in the accompanying drawings, and the names of the substituent groups arefluorine, chlorine, bromine, iodine, methoxyl, 4-morpholinyl ethyoxyl, 4-morpholinyl methyl phenyl, acryloyl amino and 2-beuteamide. The naphthlamide derivative used as the protein kinase inhibitor and the histone deacetylase inhibitor can be used for curing cardiovascular diseases, metabolic diseases, allergy, cancers and hormone-related diseases. The invention additionally provides a synthesis method of the compound. The method has the advantages that the raw materials are easy to obtain, the method is simple to operate and the method is suitable for large-scale industrial production.
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Description

Technical field:

[0001] The present invention relates to the preparation method of medicine. Specifically, it relates to a preparation method of naphthylamide derivatives of protein kinase inhibitors and histone deacetylase inhibitors. Background technique:

[0002] Naphthalene amide derivatives of protein kinase inhibitors and histone deacetylase inhibitors have therapeutic properties including cardiovascular diseases, metabolic diseases, allergies, cancer, and hormone-related diseases. The chemical name of the patented compound is: N-(2-anilino)-6-(7-substituted quinoline-4-etheroxy)-2-naphthylamide (7-position has substituent R=F, Cl, Br , I, OCH 3 , )(Note: The Chinese names of these substituents R are: fluorine, chlorine, bromine, iodine, methoxy, 4-morpholinoethoxy, 4-morpholinomethylphenyl, acrylamide, 2 -butylenamide), the structural formula is as follows:

[0003]

[0004] A large number of clinical trials have shown that this type of compound has both prot...

Examples

Embodiment

[0028] Dissolve 1.88 g (10 mmol) of the compound 6-hydroxynaphthalene in 80 milliliters of ethanol, add 4 drops of concentrated sulfuric acid, heat and reflux at 80° C. for 5 hours, and then remove the solvent under reduced pressure to obtain the compound 6-hydroxynaphthalene ethyl ester 1.98g (9.2mmol), yield 91.7%; 1.98g (9.2mmol) of compound 6-hydroxynaphthalene ethyl diate was dissolved in 10 milliliters of DMF, stirred under ice bath, slowly added dropwise containing 0.52g (21.7mmol) 5 ml of DMF solution of NaH, stirred in an ice bath for half an hour, removed the ice bath, and when the temperature returned to room temperature, slowly added dropwise 10 ml of DMF solution, stirred for half an hour, reacted at 11°C for 8 hours, then removed the solvent under reduced pressure to obtain the reaction mixture, separated by silica gel column chromatography, and the gradient of the mobile phase was: V (n-hexane): V (ethyl acetate )=4.5:1, obtain compound 6-(7-chloroquinoline-4-ox...