Clopidogrel | C16H16ClNO2S - PubChem
This review focuses on structure–activity relationship studies of molecules possessing multiple actions against thrombosis, namely, dual inhibitors of coagulation. Structure–activity relationship - Wikipedia,. The structure–activity relationship ( SAR) is the relationship between the chemical or 3D structure of a molecule and . Synthesis and Structure-Activity Relationships of Novel Direct Thrombin clopidogrel was actually more effective than aspirin in preventing death by vascular events For example, the crystal structure of FM 19 in the active site of thrombin.
Modification of these analogues led to the discovery of ticagrelor, a selective and stable non-phosphate P2Y12 receptor antagonist.
Medicinal Chemistry | Cresset
It has a fast onset of action as it is not broken down into an active metabolite like thienopyridines. In the sponsor for the phase 3 trial pulled out, where cangrelor was being tested against placebo. Cangrelor lowered stent thrombosis development more than clopidogrel. These findings were published in Cangrelor and ticagrelor are direct —acting P2Y12 inhibitors that change the conformation of the P2Y12 receptor and therefore, results in reversible platelet inhibition of the receptor.
Thienopyridines are metabolized in the liver and the intestinal to active metabolites. Metabolism[ edit ] Ticlopidine is a prodrug and is metabolized by at least five main pathways.
There is one active metabolite that has been identified and shown to have antiplatelet activity. This active metabolite is formed by a CYP-dependent pathway.
CYP2C19 and CYP2B6 are enzymes suggested to contribute to the metabolic transformation of ticlopidine to the thiolactone intermediate, 2-oxo-ticlopidine in the liver. The thiolactone intermediate is then converted to ticlopidine active metabolite via CYP oxidation where oxidation activation occurs. However the CYP enzymes that are involved in this pathway are unknown.
These metabolites may be responsible for the toxic side effects of ticlopidine. Clopidogrel is a prodrug that is metabolized by two pathways.
The other pathway of clopidogrel requires a two step hepatic CYP metabolic activation to produce the active metabolite that inhibits the P2Y12 receptor.
For example, many of the determinants of carcinogenic activity have been characterized and published.
structure activity relationship of clopidogrel
Investigators can then use the SAR to examine a novel chemical structure to see if it contains one or more of the determinants of carcinogenicity. The ability to use SARs allows for a tier approach to carcinogenicity testing.
The mutagenic potential of several classes of chemicals has also been cataloged to the extent that SARs can be used to examine novel molecules. There is a developing database to use SARs for the determination of skin and eye irritants.
In each of these cases the effective use of SARs saves time, resources, and animals. As new and better methods of determining the three-dimensional structure of genes and proteins become available, the importance of SARs for toxicology will be critical. Enzymes and proteases Enzyme inhibitors are an important group of drugs.
They are effective in therapeutic areas as diverse as cancer, depression, cardiovascular disease and pain. Protease enzymes break down proteins and peptides. Over human proteases have been identified so far. However, it is notoriously difficult to develop drugs for protease targets due to selectivity issues and property space. Ion channels Ion channels control the flow of ions such as sodium, calcium or potassium across a cell membrane.
They play an important role in regulating many physiological processes, so can be very useful targets. Protein-protein targets Protein-protein interactions are a medial step in many biological processes. Designing a compound that will inhibit these interactions is a promising way to intercept mechanisms that have an adverse effect on a disease condition.
structure activity relationship of clopidogrel - mentoreleg40's soup
The challenges of designing suitable inhibitors relates mainly to the large surface area of the proteins. The computing power required to model the proteins means that identifying suitable binding sites can be a slow process. However, there is a high therapeutic potential in designing suitable small molecules for protein-protein targets.
Working towards innovative solutions The type of protein target has a fundamental impact on the nature of a drug discovery project.