Philosophy First

About twentyfive years ago, combinatorial chemistry (or parallel synthesis) promised to change the way drugs were discovered. Most people are now somewhat disappointed with the way this has turned out. The "new technology" found some application in lead generation but, in most organizations, didn't find its way up the value chain. In most pharmaceutical R & D organizations, few medicinal chemists are actually using parallel synthesis techniques. We suspect that this is because of the complexity and somewhat inappropriate application of technology to this field. It was too hard to use if you didn't use it all the time.

So what many companies did was set up a high throughput chemistry group that understands all this complex stuff and gets to do other peoples chemistry when they need multiple similar compounds. This makes sense, given the current state of the art. However, in a discovery organization, this "handoff of chemistry" is fairly inefficient and often political and bureaucratic. There's a battle over who gets to use these free "hands."

We believe that a more attractive model is for chemists all along the value chain to perform their own parallel synthesis. This, of course, only makes sense if the chemists know how to do it. It should be almost as simple as how they do it one at a time.

Medicinal chemists could probably benefit from using parallel synthesis techniques to advance SAR exploration in 5% to 30% of their projects. This depends almost entirely on the chemistry they're doing. If you're going to return to something you haven't used in a while, it needs to accessible.


At InnovaSyn, we believe that medicinal chemists are most productive doing chemistry. They enjoy, employ, and keep up with the technology of chemistry much more than the "other technologies" of robotics, computers, automation, and equipment design. However, as demands grow for chemists to do more, make more and analyze more, there is value in these other technologies. This value is best realized when the tools it brings to chemistry are robust, easy to use and make sense to chemists. We believe that our products, from our fully functional yet versatile reactors, to our robotics systems, which offer many capabilities with unprecedented ease of use, will help meet the demands of today's chemist.

Making and testing new molecular entities (compounds) is a fundamental requirement for modern drug discovery. Over the last fifteen years, as the ability to test molecules for therapeutic activity has grown explosively, so has the need to make compounds faster and cheaper. Over that period of time, our group at Sphinx Laboratories (Eli Lilly & Co.) developed a number of ways to accomplish this task. It was done, not by developing complex instruments, but by understanding the fundamental challenges of organic synthesis and bringing the appropriate application of technology to bear on the problem. The emphasis has been on simplicity, flexibility, ease of learning and ease of use. We believe that, in the future, the tools that survive will look a lot like the tools we have developed today.

The ideas, processes and technologies used to accelerate organic synthesis have been known as combinatorial chemistry, rapid parallel synthesis and high throughput chemistry among others. Although there are similarities and overlaps in how many groups have approached this, we believe our approach to the process is unique.

A number of commercial efforts in the area of high throughput chemistry aimed at solutions that automated everything, provided lots of flexibility with complex interfaces, and were called synthesizers. This works with peptides and DNA, but as one moves into classical medicinal chemistry, with its wide variety of chemistries and outcomes, these devices stumbled and most have been relegated to storage or sold on e-bay at a few percent of their original cost.

One unique aspect in our approach is how we have incorporated liquid handling robots into the process. Ask an organic chemist to name the most time consuming part of synthesis and he will tell you that (besides meetings) workup, analysis and purification are the most time consuming. That’s where we focused our attention. We separated the process of running reactions from the tasks that can most benefit from the use of robotics. So, as high throughput chemistry moved from making large libraries, into the lead optimization process of main stream medicinal chemistry, we were able to easily adapt our technology and keep it useful. The end result is a process that utilizes many commercial solutions, but a process that drove the need to develop new solutions. InnovaSyn is ready to deliver the process and tools which greatly facilitate solution phase parallel synthesis including reactors and chemistry automation appliances.

SynthArray-24 in various configurations