Combinatorial synthesis is a technique that enables rapid synthesis of large numbers of related compounds (libraries) simultaneously, rather than making compounds one at a time. This dramatically accelerates drug discovery and lead optimization.

Key approaches:

• Parallel Synthesis:Multiple reactions run simultaneously in separate vessels using automated equipment
• Split-Pool Synthesis:Combines solid-phase chemistry with systematic splitting and mixing to generate very large libraries
• Encoded Libraries:Chemical tags or DNA barcodes track compound identity in pooled synthesis

Advantages over traditional synthesis:

• 10-100x faster compound generation
• Systematic exploration of chemical space
• Standardized synthesis and purification protocols
• Lower cost per compound due to economies of scale
• Reduced material consumption with miniaturized reactions

Library sizes vary based on project goals, chemistry strategy, and budget. We design libraries optimally sized for your specific objectives.

Typical library sizes:

• Ultra-focused libraries:5-20 compounds (close analogs around a lead)
• Focused SAR libraries:20-50 compounds (systematic variation of 2-3 positions)
• Medium diversity libraries:50-200 compounds (broader exploration)
• Large diversity libraries:200-500+ compounds (comprehensive chemical space coverage)

Most medicinal chemistry libraries contain 20-100 carefully designed analogs that balance breadth of SAR coverage with practical screening capacity. We work with you to determine the optimal library size based on:

• Screening capacity (HTS vs. low-throughput assays)
• Budget and timeline constraints
• Maturity of the lead series
• Complexity of synthesis

Turnaround times depend on library size, chemical complexity, and purification requirements. We provide detailed timelines during project planning.

Typical timelines (from design to compound delivery):

• Small focused libraries (10-20 compounds):4-6 weeks
• Medium libraries (20-50 compounds):6-10 weeks
• Large libraries (50-100 compounds):10-14 weeks
• Very large libraries (100-500+ compounds):12-20 weeks

Timeline breakdown:

• Library design and building block sourcing: 1-2 weeks
• Synthesis and workup: 2-8 weeks (depending on steps and library size)
• Purification and QC: 1-3 weeks
• Analytical characterization and documentation: 1-2 weeks

Expedited timelines are available for urgent projects. We also offer staggered delivery where compounds are released as batches become available to accelerate your screening.

We provide purified, characterized compounds suitable for biological testing. Purity specifications and quantities can be customized to your needs.

Standard specifications:

• Purity:≥85% (typical), ≥90% or ≥95% available for additional cost
• Quantity:5-10 mg per compound (standard), 1-50 mg available
• Format:Powder in labeled vials or 10 mM DMSO solutions in plates
• Characterization:LC-MS (mass and purity) for all compounds
• Additional analysis:1H NMR available upon request

Purification methods:

• High-throughput SPE (solid-phase extraction)
• Mass-directed preparative HPLC
• Normal and reverse-phase chromatography
• Crystallization for select compounds

We provide complete documentation including structures, analytical data (LC-MS traces), and compound management database files compatible with common LIMS systems.

Yes, library design is a critical component of our service. Our medicinal chemists work collaboratively with you to design libraries optimized for your biological targets and program goals.

Library design services include:

• Virtual library enumeration:Computational generation of all possible compounds from building blocks
• Diversity analysis:Chemoinformatic selection of maximally diverse subsets
• Property filtering:ADMET prediction and filtering for drug-likeness (Lipinski, Veber rules)
• Structure-based design:Docking and scoring if target structure is available
• Scaffold analysis:Privileged scaffolds and bioisostere identification
• Building block selection:Commercial availability and synthetic accessibility
• IP analysis:Patent landscape review to avoid freedom-to-operate issues

We use industry-standard software (MOE, Pipeline Pilot, ICM, etc.) and collaborate closely with your computational chemistry team if available. The result is a focused, high-quality library optimized for success.

We have broad synthetic capabilities for combinatorial library synthesis, covering most major reaction classes used in medicinal chemistry.

Common library synthesis reactions:

• Coupling reactions:Amide, sulfonamide, urea, carbamate formation
• Heteroaromatic chemistry:Suzuki, Buchwald-Hartwig, SNAr reactions
• Reductive amination:Primary and secondary amine formation
• Click chemistry:Azide-alkyne cycloadditions
• Multicomponent reactions:Ugi, Biginelli, Hantzsch reactions
• Heterocycle synthesis:Pyrazoles, pyrimidines, triazoles, benzimidazoles
• C-C bond formation:Grignard, organozinc, Heck reactions

Our chemists evaluate synthetic routes for combinatorial suitability considering:

• Reaction reliability and yield across diverse substrates
• Compatibility with high-throughput purification
• Availability of building blocks
• Reaction conditions amenable to automation

Absolutely. Most of our library projects involve SAR exploration around client-provided lead structures. We excel at translating medicinal chemistry hypotheses into practical library designs.

Our approach to lead optimization libraries:

• SAR strategy discussion:Understand your hypotheses and priorities
• Retrosynthetic analysis:Identify optimal disconnection points for library synthesis
• Building block sourcing:Identify commercially available or readily synthesizable building blocks
• Library matrix design:Systematic variation of 1-3 positions
• Control compounds:Include known actives and close analogs
• Property optimization:Balance potency goals with ADMET considerations

We maintain strict confidentiality (NDA required) and respect your IP. Your lead structures and library designs remain completely confidential. We can work under your chemical matter transfer agreement if required.

Combinatorial synthesis typically achieves 80-95% success rates, but some compounds will inevitably fail. We handle this proactively and transparently.

Our quality assurance approach:

• Reaction optimization:Optimize conditions before library synthesis using test substrates
• Analytical QC:LC-MS analysis of all crude reactions before purification
• Success criteria:Compounds must meet purity specification (typically ≥85%)
• Failure analysis:Identify patterns and root causes
• Re-attempts:Failed compounds can be re-synthesized if critical to SAR
• Transparent reporting:Complete documentation of successes and failures

Pricing models:

• Per-compound pricing:Pay only for successfully synthesized compounds
• Campaign pricing:Fixed price for the library with expected success rate disclosed

We typically achieve 85-95% success rates. If success rates fall below expected, we work with you to either optimize conditions or redesign problematic portions of the library.

Yes, iterative library design and synthesis is one of our most powerful service offerings for lead optimization. This design-make-test-analyze (DMTA) cycle approach accelerates optimization.

Iterative optimization workflow:

• Round 1:Initial focused library (20-50 compounds) exploring key positions
• Screen & Analyze:You test compounds; we analyze SAR together
• Round 2:Follow-up library (20-50 compounds) based on hits and emerging SAR
• Iterate:Continue cycles until optimization goals achieved

Advantages of iterative approach:

• Focus resources on most promising chemical space
• Incorporate learnings from each round into design
• Faster overall timeline to optimized lead than large upfront libraries
• Lower risk - test hypotheses before major investment

Typical iterative projects involve 2-4 rounds of 20-40 compounds each over 4-8 months. We can establish dedicated capacity for fast turnaround (3-4 weeks per round) to maximize velocity.

We maintain state-of-the-art equipment for automated and parallel synthesis, enabling high-throughput compound production with excellent reproducibility.

Synthesis platforms:

• Parallel reactors: 24-well, 48-well, and 96-well formats
• Automated peptide synthesizer for solid-phase synthesis
• Microwave synthesis reactors for rapid heating
• Flow chemistry systems for continuous synthesis
• Automated liquid handling robots for dispensing and transfer
• Controlled atmosphere glove boxes for air-sensitive chemistry

Purification & analysis:

• Mass-directed preparative HPLC (multiple systems)
• Automated SPE (solid-phase extraction) workstations
• LC-MS systems for QC analysis (96-well format compatible)
• Automated evaporation systems
• Plate readers and liquid handlers for compound formatting

All equipment is maintained on regular calibration and preventive maintenance schedules to ensure consistent performance.

Pricing varies based on library size, chemical complexity, purity requirements, and building block costs. We provide detailed quotes after understanding your project.

Typical pricing (per compound successfully synthesized):

• Simple libraries (1-2 steps):$500-1,500 per compound
• Moderate complexity (3-4 steps):$1,500-3,000 per compound
• Complex libraries (5+ steps):$3,000-6,000+ per compound

Volume discounts:

• 10-20 compounds: Standard pricing
• 20-50 compounds: 10-20% discount
• 50-100 compounds: 20-30% discount
• 100+ compounds: Custom pricing (30-40% discount)

What's included:

• Library design consultation
• Building block procurement
• Synthesis and workup
• Purification to specified purity
• LC-MS analytical QC
• Compound formatting and delivery
• Complete documentation

Library design as a standalone service: $5,000-15,000 depending on complexity. This can be credited toward synthesis if you proceed.

Yes, we have extensive capabilities for peptide library synthesis using both solid-phase and solution-phase methods.

Peptide library services:

• Linear peptides:2-50 amino acids using Fmoc or Boc chemistry
• Cyclic peptides:Lactam, disulfide, and thioether cyclizations
• Peptidomimetics:Incorporation of non-natural amino acids and modifications
• Peptide arrays:Spot synthesis or parallel synthesis formats
• Positional scanning:Systematic substitution at each position
• D-amino acids:All-D or mixed L/D peptides

Modifications available:

• N-terminal acetylation, methylation, or custom caps
• C-terminal amides, esters, or other modifications
• Side-chain modifications (phosphorylation, methylation, PEGylation)
• Fluorescent labels and biotin tags
• Unnatural amino acids and peptoid monomers

Peptides are purified by preparative HPLC and characterized by LC-MS (mass and purity). Typical quantities are 5-50 mg at ≥85% or ≥95% purity.

Yes, we offer compound storage, reformatting, and logistics services to support your screening and follow-up testing needs.

Compound management services:

• Storage:Secure storage of library compounds under controlled conditions (-20°C freezers)
• Reformatting:Conversion between powder and DMSO stock solutions
• Plate preparation:Cherry-picking and plate assembly for screening
• Dose-response plates:Serial dilutions for IC50 determinations
• Stability monitoring:Periodic LC-MS analysis of stored compounds
• Re-supply:Additional quantities of active compounds synthesized
• Database management:Searchable structure database with properties

Delivery formats:

• Solids in labeled vials with 2D barcodes
• DMSO stock solutions (1-20 mM) in 96-well or 384-well plates
• Custom formats available upon request

We can integrate with your compound management system or LIMS for seamless data exchange.

To develop an optimal library design and accurate quote, we need some basic information about your project goals and constraints.

Required information:

• Target structure:Lead compound structure (can be generic initially under NDA)
• SAR objectives:Which positions to vary? Specific modifications of interest?
• Library size:Approximate number of compounds desired
• Timeline:When are compounds needed?
• Budget:Budget range (helps us right-size the library)

Helpful additional information:

• Existing SAR data and active/inactive analogs
• Target information and assay details
• Property requirements (solubility, permeability, etc.)
• Quantity and purity specifications
• Patent constraints or areas to avoid

Initial steps:

• Sign NDA (mutual confidentiality agreement)
• Technical discussion call (1 hour) with our medicinal chemists
• Receive preliminary library design and quote (1-2 weeks)
• Iterate on design until finalized
• Execute contract and begin synthesis

Starting a combinatorial chemistry project with ChemContract is straightforward. We guide you through each step from initial consultation to compound delivery.

The process:

• Step 1:Initial inquiry - contact us with your project overview
• Step 2:Execute NDA (mutual confidentiality agreement)
• Step 3:Technical discussion (1-2 hours) with medicinal chemists
• Step 4:Receive preliminary library design (virtual enumeration, diversity analysis)
• Step 5:Detailed quote with timeline and deliverables
• Step 6:Design refinement and finalization
• Step 7:Contract execution and project kickoff
• Step 8:Regular progress updates during synthesis
• Step 9:Compound delivery with complete documentation

From initial contact to library delivery typically takes 8-16 weeks depending on library size and complexity.

Contact us today:
Phone: +1 (714) 732-8549
Email: [email protected]

Our combinatorial chemistry experts are ready to discuss how we can accelerate your drug discovery programs.