Medicinal Chemistry.

We have been providing expert synthetic chemistry support to the pharmaceutical and biotechnology industries for over 20 years. Our virtually integrated Drug Discovery services see the highest levels of demand, which we are able to provide through a dynamic network of trusted partners, allowing our clients to access the highest levels of expertise across all disciplines of the Drug Discovery process – in a cost-effective and synergistic way. We offer access to a range of Drug Discovery services for our clients, from Synthetic Chemistry support, through to all aspects of fully collaborative Medicinal Chemistry programs. Our expert scientific team, which enjoys the benefit of substantial and varied experience from across the industry, focusses on providing intellectual input and enabling the rapid advancement of projects.

Method

At Charnwood Molecular we employ an iterative “Design-Make-Test-Understand” cycle to our drug discovery projects.

Tools

It’s crucial to our success to use appropriate data tools, such as Stardrop from Optibrium.

Calculations

In addition, we use in-silico calculations of physical properties e.g. LogP, TPSA, MWt of all proposed target compounds.

Our Stages

Progressing through our Design-Make-Test-Understand Cycles enables efficient exploration of chemical space.

Target Identification and Validation.

Rapid synthesis of biological tool compounds [in milligram to multigram scale] to enable pre-clinical scientists to evaluate novel mechanisms to provide robust Target Evaluation on which to build a successful drug discovery project. 

Hit Identification and Evaluation.

We use a range of in silico techniques to identify new hit series, including virtual screening against an X-ray crystal structure or homology model, or scaffold hopping approaches based on a specific pharmacophore or the electrostatic field of an existing ligand. We also provide activity confirmation through compound resynthesis, as well as hit triage based on our experience of drug-like properties, followed by early exemplification (i.e., analogue-by-catalogue or wet chemistry) to provide initial SAR and clearly define the hit expansion strategy.

 

Hit identification 

  • Using in-house expertise and data analytical tools such as Stardrop, our experienced medicinal chemists efficiently evaluate the output from a High Throughput Screen (HTS) or targeted screen to identify promising chemical series with properties suitable for further optimisation. 
  • Series are evaluated and prioritised for synthetic effort based upon synthetic tractability, appropriate physical chemical properties and ligand efficiency metrics.
  •  Re-synthesis of HTS  “actives” is recommended to provide fully characterised compounds which enables confirmatory biological retesting and preliminary ADME screening to provide additional confidence to commence a synthetic Hit to Lead programme.

 

Hit-to-Lead.

Medicinal chemistry project leadership coupled with a highly experienced team of synthetic and medicinal chemists to support successive rounds of the design-make-test-understand cycle, providing clear strategic direction based on a thorough understanding of existing data and predefined project milestones. We can also make use of a series of project-proven relationships with leading third-party providers, many co-localised, to identify and optimise against specific liabilities, including ADME/Tox and PK liabilities, allowing us to rank emerging hit series for LO.

  • We synthesise bespoke compounds and use modern parallel synthesis equipment to build focused libraries to establish series specific Structure Activity Relationships (SARs).
  • We also adopt scaffold hopping capabilities to generate new SARs to move projects into free Intellectual Property (IP) space.
  • With our partners we routinely assess key ADME/Toxicology liabilities to allow us rank each hit series for rapid Lead Optimisation.

Lead Optimisation.

Our team of experienced Medicinal Chemistry Group Leaders have an established track record for the progression of compounds through LO to candidate nomination across a range of different target classes. At the beginning of LO, we work in collaboration with our clients to clearly define the target candidate profile for their project, once again employing an iterative design-make-test cycle, as shown below, to enable multiple parameter optimisation with the aim of delivering a pre-clinical candidate.

Lead Optimisation: 

  • Working collaboratively with partners, we identify a suitable Candidate Target Prolife (CTP) consisting of optimal balance of key biological, ADME, Toxicology and physical properties.
  • Our project leaders communicate regularly with clients to analyse data and ensure rapid progression of the most promising compounds 
  • In collaboration with clients, we input our extensive Medicinal Chemistry knowledge and experience gained in the Pharma and Biotech areas and by using data analytic tools such as Stardrop to ensure that progression through lead optimisation is seamless and efficient in the time scale required. 
  • Our chemists have access to Reaxys databases and use their extensive knowledge of synthetic chemistry to design efficient and tractable synthetic routes to prepare compounds for biological and ADME screening in a timely fashion.
  • We employ a combination of traditional and parallel synthetic, analytical and purification equipment and techniques to rapidly prosecute hit series to identify candidates for clinical evaluation.
  • All experimental work is written and stored securely in electronic laboratory notebooks and available for subsequent patents and publications as required.

Our success stories.

Case studies
Medicinal Chemistry

Medicinal Chemistry Lead Optimisation (LO) 1

view case study
Medicinal Chemistry

Medicinal Chemistry: HIT Finding

view case study

More Services.

Charnwood Molecular offers a range of additional services, including Process Research & Development, Medicinal Services and Grant Funding Partnerships. Find out more about our services.

Process Research & Development

Our Process Research Team has over 100 years of combined experience.

Process Research and Development

Custom Synthesis

Our talented synthetic chemists have been delivering challenging molecular research for de

Custom Synthesis

Grant Funding Partnerships

We have always had a unique understanding of the nature of grant-funded partnerships.

Grant Funding Partnerships

Contract Research including Route Development and Route Optimisation

For your contract research needs, get in touch with Charnwood Molecular today.

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