Compounds with super-aspirin effects

a technology of compound and aspirin, which is applied in the field of compound with super-aspirin effects, can solve the problems of reducing the dose, poor adhesion, and inability to solve the aspirin resistance problem of enteric coated aspirin, and achieves the effects of reducing low density lipoprotein cholesterol and triglycerides, reducing hdl, and inhibiting tcipa

US20140024681A1Inactive Publication Date: 2014-01-23SOLVOTRIN THERAPEUTICS LTD
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Patent Information

Authority / Receiving Office
US · United States
Patent Type
Applications(United States)
Current Assignee / Owner
Publication Date
2014-01-23
Estimated Expiration
Not applicable · inactive patent

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Abstract

A compound having the structural formula (I) and pharmaceutically acceptable salt and / or hydrates thereof, (I) wherein Y is an arylester or an C1-C8 alkylaryl ester, selected from the group consisting of: benzene, toluene, xylene, benzoic acid, benzoate, nicotinate, isonicotinate and halobenzene, which can be unsubstituted or substituted with at least one nitric oxide releasing group; and / or at least one of hydroxide, —Cl, —Br, a C1-C8 alkyl, benzyl, a C1-C8 alkoxy, benzyloxy, —NHC(O)R, —NH2, —NO2—ONO2, —(CH2)nONO2, —OC(O)[(CH2)n]cyclicONO2, —OCOArONO2, —OCOAr(CH2)nONO2 or a C1-C5 haloalkyl ester, wherein R is a C1-C8 alkyl or a C1-C8 alkoxy group, n=1-8 and m=3-10, to produce a super-aspirin effect.
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Description

FIELD OF THE INVENTION

[0001] The invention relates to aspirin prodrug compounds that are capable of providing a super-aspirin effect which provides an additional antiplatelet effect over the antiplatelet effect of any aspirin released. In particular, the compounds are useful in conditions where aspirin has traditionally thought to be ineffective, such as conditions where inhibition of tumor cell induced platelet aggregation (TCIPA) is desired. The compounds may be used in cardiovascular and / or anticancer applications.DESCRIPTION OF RELATED ART

[0002] Aspirin is an effective antiplatelet drug, reducing the risk of myocardial infarction (MI), stroke or death by approximately 25% in patients who are at increased risk of cardiovascular (CV) events. However, in some cases less than expected inhibition of platelets by aspirin has been referred to as aspirin resistance.a Aspirin resistance levels have been reported to range from 5 to 63% in various studies.bc

[0003] A number of potential mecha...

Examples

Embodiment Construction

[0092]The present inventors have demonstrated that the compounds used within the context of the present address aspirin resistance problems in 3 major ways:

(i) the prodrug compounds used herein demonstrates significantly better GI tolerability when compared to aspirin;

(ii) in the case of ST0702 (ISANA or the “Nicotinate”), data obtained in a Non-Human Primate study indicate that there are surprisingly good effects of the drug in-vivo; and

(iii) in the case of the prodrugs used within the context of the present invention, and exemplified by the data on the nicotinate compound ST0702, there are advantageous and desirable non-aspirin antiplatelet effects produced by a metabolite of the prodrug compounds.

[0093]It has been found that because platelets are activated by multiple pathways, these non-aspirin antiplatelet effects supplement the aspirin effects to reduce platelet activation, particularly in disease states with high levels of inflammation or in patients with genetic polymorphism...