Synthesis of compounds in support of Drug Discovery is at the heart of our chemistry services.
Synovo has a team of 12 chemists covering key aspects of synthesis, analytics and formulation to ensure that we can deliver necessary compounds and dose forms to our pharmacology studies, assays and customers.
Synthesis activitites include:
- Preparation of samples of small molecules as drug-like molecules or as reagents for screening assays
- Preparation of building blocks and intermediates for other programs
- Design and synthesis of focused libraries and analog series for lead optimisation
- Production of patent examples or validation of patent methods and products
- Development of scale-up methods
- Production of salt forms
- Purification and characterisation of specific enantiomers
- Synthesis of metabolites and analytical standards including potential impurities for both production and pharmacokinetic studies.
In the field of small molecule drugs, variation and assay are essential to both finding improved compound, but also in claiming sufficiently broad example space in patents.
There are three key aspects of this process: making the variations; obtaining data on these analogs such that a direction can be deduced for further work; and, modelling these results to identify non-obvious next-steps.
Of these processes, the actual synthesis step is highly dependent on the series and no-two series are alike. Thus, while we have clever and efficient chemists, each case is very much individual and difficult to generalise. However, the turn-around of assay data back to chemists is a more systemic issue and this is one that Synovo has optimised.
We have established procedures such that when we are using in house assays or in vivo models, we can enter newly made compounds into assays almost immediately. Thus, chemists receive feedback on their compounds before they have put in place the next round of products. This shortens the iteration cycle and reduces the effort expended on less promising structures.
In the field of SAR modelling, we have generally found that our clients and partners which to retain this aspect for themselves or their own contractors and consultants. While Synovo collaborates with some of the leading physical chemists and modelling companies, we do not generally have these skills in house. We are, however, happy to recommend sources of modeling input and structural biology when appropriate.
All Synovo compounds and samples are subject to a range of characterisations to ensure identity, stability and purity.
These measures include:
- NMR - generally 13C and 1H but other modes are possible
- MS - Multiple modes with MSn fragmentation
- Purity by ELSD (Evaporative Light Scattering Detector) coupled to UV and MS detection as needed.
- IR, Optical Rotation and Elemental analysis
- Validation of formulation content and stability of LCUV/ELSD as required
Production of compounds and formulations for patent purposes
Synovo chemists are familiar with the requirements for the protection of intellectual property. Within the IP space, we have the following offerings:
- The preparation of patent examples either in written form only, or with accompanying synthesis
- The testing of third party methods reported in patents
- Validation of patent claims including associated biological tests
- Preparation of patent text and critical review
- Searching of patents for relevant disclosures and interpreting their practical implications
Pharmacology is a central part of Synovo’s offering. One of the aspects that helps make Synovo unique in the Pharmacology services space is that we conduct all our studies with medicinal chemistry support. This makes the studies more likely to succeed and generate insight.
Our chemistry services support pharmacology in many ways including:
- Formulation and stability of the dose form
- Selection of appropriate salts and their preparation where needed
- Preparation of metabolites and standards
- Interpretation of bioanalytics spectra and validation of assay methods
- Interpretation of AI purity and properties if performance is not as expected
- Re-purification of AI if needed
Non-clinical or experimental formulation
A key criterion for any drug development or optimisation is the issue of whether the active ingredient can be stable formulated and delivered in a suitable form.
Similarly, early phase efficacy studies are more convincing if they are conducted with formulation excipients that are the same or similar to those used in commercial products. This is because the use of "approved" excipients simplifies the acceptance of both pre-clinical efficacy data sets and associated toxicology studies while presenting little additional regulatory burden should the candidate be found to depend on particular excipients for its effective formulation.
Synovo has many of the major excipients in its collections and is able to offer experimental formulation services in support of its general pharmacology offering.
A key aspect of formulation is making it possible to accurately administer the substance. Given that many drug like molecules are not inherently soluble, it is not always necessary to prepare solutions. Rather, in some cases, emulsions or suspensions can be more stable and consistent. While "formulation" in this sense is broadly practiced, it is not widely taught and many formulation approaches are extremely specific to compound types.
What makes Synovo unique in this context is not only that we find adequate means to formulate compounds in a "Pharma-like" manner, but that we can do it with extremely low amounts of material. Central to our approach is that the production of the substance is often one of the most expensive steps and this material has to be used very carefully and not wasted.
Synovo has extensive experience in preparing experimental oral dose forms that either provide useful and stable results in oral application, or simulate final pharmaceutical dose forms (i.e. capsules, enteric coated capsule etc.).
Analytics and Pharmacokinetics
Synovo analytics has two main activities, support of Pharmacology studies, and support of compound and formulation quality assays.
Synovo is a well known supplier of Pharmacokinetics, distribution and biological stability assays. In particular, we offer one of, if not the fastest, PK services in the industry. Check with us our "PK in a day" offer.
We use a combination of Agilent HPLCs and Sciex triple quad mass spectrometers to deliver fast-turnaround PK and distribution data.
Where required, we combine PK studies with provision of experimental formulations to establish the best means of applying a given compound series in vivo. Routine in our bio-analytics offering are:
- Compound organ distribution (gut, brain, CSF, liver, inner ear, eye are common examples).
- Plasma/whole blood partition
- Quantification of metabolites where standards are available
- Quantification of elimination routes if required (bile, feces, urine) with hydrolysis of conjugates when needed