Anti-allergic benzocycloheptathiophene derivatives

An allergy and benzocycloheptane technology, applied in the direction of active ingredients of heterocyclic compounds, drug combinations, medical preparations containing active ingredients, etc.

Active Publication Date: 2016-06-01
FUJIAN MINDONG REJUVENATION PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Second, they are highly lipophilic and readily cross the b

Method used

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  • Anti-allergic benzocycloheptathiophene derivatives
  • Anti-allergic benzocycloheptathiophene derivatives
  • Anti-allergic benzocycloheptathiophene derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0277] Example 1. Synthesis of 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]-4,9-dihydro-1-thia-benzo[f] Azulene-10-one.

[0278]

[0279] Scheme I gives 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]-4,9-dihydro-1-thia-benzo[f] Azulene-10-one ( 5 ), which passes through norketotifen ( 2 ) and 3-bromomethyl-5-methyl-pyridine ( 4 ) Alkylation. By treating 3,5-lutidine with NBS and AIBN in a solvent mixture of chloroform and carbon tetrachloride ( 3 ) to obtain the compound ( 4 ). Norketotifen ( 2 ) was obtained by treating ketotifen with 1-chloroethyl chloroformate and methanol, respectively. Norketotifen ( 2 ) can also be obtained by treating ketotifen with vinyl chloroformate. Similarly, norketotifen ( 2 ) can be obtained by treating ketotifen with 2,2,2-trichloroethyl chloroformate (see US Patent 7,557,128). Alternatively, norketotifen ( 2 ) can be obtained by treating ketotifen with cyanogen bromide (von Braun dealkylation) or ethyl chlorofo...

Embodiment 2

[0280] Example 2. Synthesis of 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]-4,9-dihydro-1-thia-benzo[f] Azulene-10-one. (Synthetic Scheme II)

[0281]

[0282] In protocol II, norketotifen ( 2 ) and 5-methyl-nicotinic acid ( 6 ) acylation to generate compound (7), and then available phosphorus oxychloride and sodium borohydride reduction can obtain 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]- 4,9-dihydro-1-thia-benzo[f]azulene-10-one ( 5 ) (please refer to Journal of Medicinal Chemistry 1994, 37, 2697-2703).

Embodiment 3

[0283] Example 3. Synthesis of 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]-4,9-dihydro-1-thia-benzo[f] Azulene-10-one. (Synthetic Scheme III)

[0284]

[0285]

[0286] In Scheme III, the compound ( 8 ) and Grignard derivatives prepared from 3-(4-chloro-piperidin-1-ylmethyl)-5-methyl-pyridine (references: DrugsoftheFuture1996, 21(10):1032-1036 and SpanishPatentES2120899) ( The reaction of 9) provides the alcohol ( 10 ), the alcohol ( 10 ) through H 2 SO 4 Final elimination of HBr and dehydration to yield 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]-4,9-dihydro-1-thia-benzo[ f] azulene-10-one ( 5 ). Alternatively, alcohol ( 10 ) is dehydrated by HBr to generate the compound ( 11 ), the compound ( 11 ) was treated with piperidine and potassium tert-butoxide to provide the compound ( 12 ). compound ( 12 ) is treated with aqueous hydrochloric acid to generate 4-[1-(5-methyl-pyridin-3-ylmethyl)piperidin-4-ylidene]-4,9-dihydro-1-thia-benzo[f ]...

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PUM

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Abstract

The present invention provides allergy and allergic reaction inhibitors, specifically the compound of the present invention as described in the following chemical formula I. The method for treating allergic reaction or allergic reaction disease or disorder comprises administering to a subject in need thereof for treatment An effective amount of a composition comprising a compound of formula I or a pharmaceutically acceptable salt, solvate or prodrug thereof and a pharmaceutically acceptable carrier, vehicle or excipient.

Description

Background technique [0001] The statements in this section merely provide background information related to the present disclosure and may not constitute prior art. [0002] Allergy is a complex disease. A variety of immune cells and inflammatory mediators contribute to the initiation and manifestation of allergic diseases. In addition to blocking histamine H1 receptors, anti-inflammatory effects have increasingly been recognized to play an important role in the management of allergic diseases. The anti-inflammatory effects include stabilizing mast cells (preventing mediator release), blocking lipid mediators (such as platelet-activating factor (PAF) and leukotrienes), inhibiting adhesion molecules, and inhibiting eosinophils and CD- 4 T cells. [0003] Allergic diseases have reached infectious proportions worldwide. Allergic diseases such as asthma, rhinitis, or atopic dermatitis affect at least 8%-16% of the population, with an annual economic burden of $12.7 billion, $1...

Claims

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Application Information

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IPC IPC(8): C07D417/10A61K31/445A61K31/4545A61P11/06A61P11/08A61P17/00A61P27/02A61P27/14A61P37/08
CPCC07D409/14A61K31/445A61K31/4545A61P11/00A61P11/02A61P11/06A61P11/08A61P17/00A61P17/04A61P27/02A61P27/14A61P37/08
Inventor 林童俊辛军
Owner FUJIAN MINDONG REJUVENATION PHARMA
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