C01C did nine synthesis experiments from route design to specific experimental procedure setting, which took several months, and finally obtained the target product with a total yield of 25%.

Nine synthesis experiments, one for four days and three nights, took more than a month.

The route design took three months, three months of thinking, and more than a month of practical operation, and the chemistry trio got the preset product.

Before the route was designed, there was a large amount of literature research and computer-aided verification, and the time required was difficult to estimate.

"I work in an organic outsourcing company, making more than 200 compounds a year, and at the center, I estimate that I do up to three a year. Cheng Haonan said with great emotion that there is a kind of rush for two lives.

"Where do you work, what suits your liking?" asked Shen Qi.

"Of course, it's with Boss Shen!" Cheng Haonan replied without thinking, "The work engaged in the center, starting from the route design, and getting the target product step by step, is the real organic chemistry, and we do scientific research work with thought and soul." At outsourcing companies, we do manual labor. ”

Lao Yan, who had tasted the sweetness, asked: "The sample of C01C has come out, and the total yield is 25%, so our task is completed, right?"

At that time, C01B did this, Shen Qi asked Lao Yan to write a paper, publish it, and then sell the patent.

Shen Qi said: "The task of organic chemistry is completed, and the next step is biochemistry. ”

"Biochemistry, pharmacology, pharmacokinetics, Lao Cheng and I don't know much about it. Lao Yan said the blind spot in his and Cheng Haonan's knowledge reserves.

Shen Qi patted Lao Yan's shoulder: "Yan Gong, what you said is very amateurish, you don't know how to learn? Don't you two have a master's degree, you never thought of studying for a doctorate and charging yourself? Biochemistry is interconnected in many places, intersecting with each other, you two can go to a doctorate in biochemistry or medicinal chemistry." ”

Lao Yan smiled: "What, actually, I also know a little bit about biochemistry, after all, I am a top student in the School of Chemistry, and among the chemistry students, my biology grades are the best." ”

Cheng Haonan said: "I have not studied pharmacology and pharmacokinetics systematically, but the outsourcing company I worked for before made compounds that were all prototypes of drugs, and in fact there were no certified and approved drug samples. I've never eaten pork, and I've never seen a pig run? ”

Shen Qi: "Oh, you two are really geniuses, you understand it at once?" Okay, you two worked hard and did the activity experiment of C01C." After the results of the activity experiment come out, you two write the paper, who is the corresponding author and who is the first work, you two discuss it yourself. ”

Both Lao Yan and Cheng Haonan know that C01C is an expected drug.

Glycogen synthase kinase-3β has been associated with a variety of diseases, including diabetes, Alzheimer's disease, immune diseases, cancer, and more.

The use of C01C was set by Shen Qi as a glycogen synthase kinase-3β inhibitor.

In fact, scientific research institutions, pharmaceutical companies, and CROs in Europe, the United States and Japan are all studying glycogen synthase kinase-3β inhibitors, and the research results of the research team of Novartis in Switzerland have been officially reported.

Three years ago, the Novartis research team reported a new compound CX017721 that has shown good therapeutic effects in Alzheimer's disease patients in Phase IIB clinical trials in Europe.

Three years on, the Swiss pharmaceutical giant's research team has not continued to report CX017721 results of phase III clinical trials in Europe, perhaps not yet in phase III, or is ongoing, or may have failed.

Under the premise that basic research is recognized, the development of a new drug, from the initial target setting to the drug market, takes three to five years is the speed of light, and the time taken ten years is the average speed.

In other fields, the strength of the company's R&D team is difficult to compare with that of formal scientific research institutions.

With the exception of the pharmaceutical industry, there are many Nobel Prize winners in the R&D teams of international pharmaceutical giants.

Shen Qi's design of C01C also got some inspiration from the research results of the Novartis research team in Switzerland.

The Swiss team has not moved for three years, while the chemistry trio of the Chinese Yanda team continues to move forward.

The inhibitory activity of glycogen synthase kinase-3β of C01C is the key, and the basic experimental instruments for activity testing are available in Shen Qi's laboratory.

"Baki's Kinase-Glo test method, who will?" asked Shen Qi.

"I'll do this, base the. Cheng Haonan volunteered to take a 96-well plate and test it in a buffer solution.

"Lao Cheng, yes, this is very capable. "Old smoke has become a spectator.

"The five-year career as an organic migrant worker has been somewhat rewarding, and I have done basic research and route design, but I am still good in terms of specific application and practical technology. Cheng Haonan gradually gained a bit of self-confidence as a scholar, and the influence of the working environment and the people he came into contact with around him could not be ignored.

Mix with scientific research migrant workers every day, and at most be a migrant worker boss.

When you work with people who have ideals and pursuits, the scenery will be farther and more magnificent.

Cheng Haonan skillfully took DMSO solutions of different concentrations of C01C samples, diluted them with buffer solution, and added 2 μL of enzyme solution to each well, as well as buffers containing substrate and ATP.

Incubate at 30 degrees Celsius for 30 minutes, stop the enzyme reaction with Kinase-Glo reagent, and Cheng Haonan completed all the operations by himself and recorded the chemiluminescence intensity.

The student's hands-on ability is really strong, otherwise he would not be able to be the experimental team leader of an organic outsourcing company.

"The mode of inhibition of the compound was determined by enzyme kinetic experiments, also tested based on chemiluminescence, by plotting, the straight line intersected on the y-axis, the inhibitor was ATP-competitive, the linear intersected on the x-axis, and the inhibitor was non-ATP-competitive. Through the experimental data, we can see that the inhibition of C01C does not compete with either ATP or substrate, so ...... "Cheng Hao's Nankou said a bunch of things like a hanging river, and said that the key position was stuck.

Further discussion, it is biased towards medicinal chemistry, and Cheng Haonan's theoretical reserve is insufficient.

Shen Qi said: "I think that from its double reciprocal chart, it can be inferred that C01C is actually a non-ATP-competitive inhibitor, and the benzothiazinones substituted by 2 long lipids as a new class of glycogen synthase kinase-3β inhibitors also need to be verified by medicinal chemistry and biochemistry, as well as a series of tests such as animal experiments and clinical experiments." ”

"The further back you go, the stronger the color of medicine becomes, and the three of us can't do it. We're done in the lab, so let's sort through the data and start writing the paper. Shen Qi made a summary.

When it comes to writing papers, Lao Yan is very interested: "I am the best at writing papers." ”

From the experience of C01B, it can be seen that after writing and publishing papers, you can sell patents again.

But this time Shen Qi is not in a hurry to transfer scientific research results, C01B is a compound that has the potential to become a smoking cessation drug, and C01C is facing a wider range of people, diabetes patients, Alzheimer's disease patients, immune disease patients, cancer patients, too many.

This benzothiazinone compound has the potential to develop into a family, like Janssen's classic product fentanyl, and a larger family of drugs with a wider range of applications.

At Shen Qi's level, how can he not be able to distinguish between priority and priority, and he can't see the estimated prospects of a scientific research product?

"C01C is no longer for sale, and we will continue to carry out the next research. Shen Qi said that he had an idea in his heart.

"Boss, you just said that animal experiments, so many phases of clinical trials, the three of us can't handle it?" Lao Yan wondered.

"yes, so we need to make the most of external resources. You don't have to worry about this matter for the time being, write your dissertation and seize the academic commanding heights first. The research results are here, and when we have the ability, we will do the work later. Shen Qi finished arranging the work of the laboratory and left.

Lao Yan said to Cheng Haonan: "Boss Shen set up an animal laboratory before and recruited Lao Tu to be an animal experimenter. Later, Boss Shen changed his strategy and said that we would only do route design and sample synthesis at the laboratory stage. Now, Boss Shen has changed his strategy again, this ...... The boss's mind is really hard to figure out. ”

"The big guy is like this, when you become the big guy, you will understand. ”

"It's like you've been a big guy!"