Sat. Jul 20th, 2019

How to 'top-up' the pharmaceutical industry | Science

How to 'top-up' the pharmaceutical industry | Science



To make sumanirol, the powerful pharmaceutical Pfizer needed enough hydrogen gas to fill a stadium and thousands of liters of toxic ammonia. And the whole experiment had to be done at 35º. Now, a team of American chemists has manufactured this drug, presented as a possible cure against Parkinson's, with an experiment that "could do with their children in the kitchen."

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That's what it holds Phil Baran, professor at the Scripps Research Institute in La Jolla (California) in a Article published this week in Science in which he outlines his innovative method to produce the chemical components that form the basic blocks of drugs.

The repercussions could be immense: "This opens the door to the preparation of some really promising drug candidates," says David Hickey, assistant professor of research at the University of Utah and co-author of the article. He explains that Pfizer has been forced to discard many of the drugs envisaged for its development simply because they were too difficult, dangerous and expensive to manufacture. The Sumanirol is one of them, parked more than a decade ago precisely for those reasons.

In fact, the research team - an eclectic mix of scientists from several US universities, from the Development and Research section of Pfizer and the Chinese pharmaceutical company Asymchen - has already made progress since its beginning demonstration article. Currently, some of them have started working on the manufacture of four drugs with a view to future clinical trials, says Hickey. Although they are reluctant to specify what these drugs are specifically, Baran reveals that one of them is related to oncology and the other to immunology.

The history of this advance begins in fact with batteries. Today, lithium-ion batteries are everywhere, from mobiles to computers, to electric cars. They are often a bright silver color and look small and light in the hand, like any other battery, but their innocuous facade hides a danger. Pure lithium can explode or burn if it comes in contact with air or with Water. What's more, the chemical treatment of lithium often requires ammonia, a toxic and corrosive compound whose vapors can be deadly.

Battery technology

It has taken decades of research to safely and efficiently mass produce lithium batteries, which have culminated in the understanding of the solid electrolyte interface (SEI). The SEI, which can be as tiny as a hundredth part of the thickness of a human hair, is a protective layer that forms inside the batteries, and it is known that it is vital for the efficient operation of these, especially its ability to recharge . The scientists made the surprising discovery that there is a connection between the chemistry of the SEI and the manufacture of drugs, through a process called Birch reduction. This was a revelation. "The bulb went on," Hickey recalls. "We can apply the same technology used in lithium-ion batteries to solve the drug problem."

"This opens the door to the preparation of some really promising drug candidates," says David Hickey, co-author of the article.

It has not been easy. At first, the Scripps team had the feeling that it was dealing with an impossible problem. "It took us a long time to get any conversion or hope to get something other than the simplest aromatics," says Baran. "We tested all the conditions we could." The key was found in the additives, the added components that allow to improve the chemical processes. The scientists, inspired by the SEI technology, discovered the correct additives and saw that the product of their reactions increased drastically in less than a week. From then on, progress was made.

Most significantly, the method allows scientists to synthesize drugs in large quantities. They made 10 grams of sumanirol, then one hundred, and finally one kilo in the laboratory of Asymchem. Once the method is mastered, the production capacity is almost unlimited. "We can do it on an industrial scale," says Hickey.

The team expects the ease with which their method worked - the final figure of their article announces a "cheap and solid" and "technically simple" method - encourage others. Baran tells that the drug hunters, as they are known in the sector, had been dissuaded by the danger and the cost of the old methods. Only gigantic companies could even try to synthesize certain drugs. Believe that the field has now opened wide. "Basically, we have democratized profoundly reductive chemistry."

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