The new COX-2 inhibitor AZGH101 is born!
March 26, 2018 Source: CPhI Pharma Online Author: small fan medicine
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];What is a COX inhibitor? What disease is it used to treat? AZGH101, a new drug that is seen in preclinical studies, may raise such questions.
COX, a cyclooxygenase, biologically functions to convert fatty acids in the human body into the adult essential fatty acid, arachidonic acid, to activate subsequent biological reactions, and finally to synthesize prostaglandins (PGs). PGs are inflammatory and pain response factors in humans. Therefore, inhibition of the synthesis of COX will reduce the synthesis of PGs and provide an anti-inflammatory and analgesic medical treatment effect.
At present, COX inhibitors commonly used in clinical practice are also often called antipyretic analgesic and anti-inflammatory drugs, namely non-steroidal anti-inflammatory drugs (NSAID), mainly including fenbide, naproxen, indomethacin and pyridin. Roxicam, ketorolac. Traditional NSAIDs are selective and non-selective. Because the human body's COX has three isoenzymes, namely COX-1, COX-2 and COX-3. Selective NSAIDs are selected to primarily inhibit an isoenzyme. In addition, the physiological function of COX-1 is mainly to protect the gastrointestinal mucosa of the human body. COX-2 is involved in the inflammatory process in macrophages. COX-3 is similar to COX-1, but when it is inhibited, it has a solution. Thermal effect.
The Seyed Mohsen Foroutan team at Shahid Bakhshti University School of Medicine found that traditional selective COX inhibitors have more or less cardiovascular side effects, such as rofecoxib and valdecoxib, which have been withdrawn from the market; at the same time, COX-2 is inhibited. After that, it can reduce the risk of colorectal cancer, breast cancer and lung cancer, prevent the occurrence of osteoporosis, and delay the progression of Alzheimer's disease. The team then designed and synthesized a new selective COX-2 inhibitor. Through a series of pre-biochemical experiments, a new drug, AZGH101, was found (Fig. 1). This new ketoprofen derivative inhibits acetylcholinesterase by about 10 times greater than ketoprofen, and the selectivity index (COX-1 /COX-2 inhibition potency) is also significantly improved compared to the latter. Therefore, the team further evaluated the pharmacokinetic characteristics of the drug.
Figure 1 Chemical structure of AZGH101
First, the AZGH101 sample was synthesized, and the purity of the structural formula of the LCMS detector was used to detect the purity by UV and HPLC (Fig. 2), which was over 99%, and then the subsequent physical and chemical properties such as melting point, water solubility and oxidation stability were tested. Pharmacokinetic tests such as half-life and plasma partition rate (Table 1).
Figure 2 AZGH101 purity test, left: UV; right: HPLC
At the same time, in order to study the half-life and other indicators, the experiment was carried out simultaneously in female and male rats (Fig. 3).
image 3
The results of physicochemical experiments in the study showed that AZGH101 is a lipophilic body. The results of pharmacokinetic studies showed that there was no gender difference in the physiological data of the drug in Wistar rats. In order to better explain the pharmacological properties of the drug, it is necessary Further verification of its toxic side effects and pharmacokinetics in other animals will lay the foundation for future use in the market.
references:
Hoda Bahmanof, Simin Dadashzadeh, et.al. Physicochemical, Stress Degradation Evaluation and Pharmacokinetic Study of AZGH101; a New Synthesized COX2 Inhibitor after IV and Oral Administration in Male and Female Rats [J]. Iranian Journal of Pharmaceutical Research , 2018, 1 ( 17): 115-123.
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