Cyclopropyl in drug structure

The chemical structure of cyclopropyl rings is different from that of straight-chain aliphatic hydrocarbons and other polyaliphatic rings. Cyclopropyl rings are often used in drug molecular design, and they play a variety of roles in drug molecules:

1:To enhance the efficacy of a drug;
2:Reduce off-target effect;
3:Metabolic stability;
4:Increased blood-brain barrier permeability;
5:Decreased plasma clearance rate;
6:Increased affinity for receptors;
7:Limiting peptide/mimic peptide conformation,
Limiting the hydrolysis of polypeptides;
8:Improved drug dissociation (pKa)

One: Infectious diseases

Infectious diseases are the most important application field of cyclopropyl drugs. These drugs can be used for bacterial, respiratory, otolaryngological, gram-bacterial and AIDS diseases. However, seven of the nine cyclopropyl drugs on the market since 2010 have been used to treat hepatitis C. This also makes NS3/NS4A targets another important target for cyclopropyl drugs after DNA topozymes (TOP) and HIV-1 virus reverse transcriptase (RT).

Two: Respiratory diseases

Cyclopropyl respiratory diseases also play a major role. Two recent cyclopropyl drugs in this field are DNA topological enzyme (TOP) inhibitors, Nemonoxacin Malate, which was marketed in Taiwan, China in 2014, and Zabofloxacin Hydrochloride, which was marketed in South Korea in 2015, mainly used for the treatment of pneumonia and bacteria-induced lung disease.

Three: cardiovascular and cerebrovascular diseases

Hyperlipidemia is an important risk factor for cardiovascular diseases. Hypercholesteremia, especially high levels of low-density lipoprotein cholesterol (LDL-C) in the blood, may deposit on the arterial wall and form plaques, causing atherosclerosis. At the same time, too high LDL-C may cause coronary heart disease. Cholesterol in human body is synthesized by acetyl-Coa (CoA), an intermediate product of metabolism, through A reaction of about 30 steps. In this process, HMGCR is the rate-limiting enzyme. This enzyme inhibitor can inhibit the biosynthesis of cholesterol and thus reduce the cholesterol level in the body. Cyclopropyl piece cut statin drugs (Pitavastatin) is a kind of this enzyme, the drugs have been approved for the treatment of patients with primary hyperlipidemia or mixed dyslipidemia as the diet support therapy, in order to reduce the total cholesterol (TC), low-density lipoprotein cholesterol (LDL – C), apolipoprotein B (Apo B), triglyceride (TG), and increase high density lipoprotein cholesterol (HDL – C).

Four: Mental disorder

Cyclopropyl psychotropic drugs have a long history. Concordia developed Tranylcypromine Sulfate, a monoamine oxidase (MAO) inhibitor, to treat severe depression, was first marketed in the United States in 1961. However, in the 21st century, cyclopropyl drugs have made few breakthroughs in this field.