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The most medchem reliable source of carboxylic acids replacement
1 280 compounds
Together with The Institute of Cancer Research, London, we have developed a powerful FBDD tool for searching carboxylic acid bioisostere (CAB) fragment hits. This approach provides an alternative to the conventional replacement of the carboxylic acid moiety during lead optimisation. While the -COOH group is present in several approved drugs and significantly contributes to target binding, carboxylic acids can limit cell permeability and become a tox liability. Even though many carboxylic acid bioisosteres have been reported, the outcome of any bioisosteric replacement cannot be readily predicted. This collection of CAB-frags provides a screening tool kit to identify carboxylic acid surrogates at the very outset of a drug discovery campaign to find hits that form critical binding interactions to a target of interest that may translate to a larger lead molecule.
Typical Formats
Catalog No.
CAB-1280-10-Y-100
Compounds
1 280
4 plates
Amount
10 µL of 100 mM DMSO solutions
Plates and formats
384-well plates Greiner Cat. No 781280, first two and last two columns empty, 320 compounds per plate
Price
Catalog No.
CAB-1280-25-Y-100
Compounds
1 280
4 plates
Amount
25 µL of 100 mM solutions in DMSO
Plates and formats
384-well plates Greiner Cat. No 781280, first two and last two columns empty, 320 compounds per plate
Price
Download SD file
Key features
- Covers all reliable CAB replacements
- Experimentally confirmed solubility in PBS buffer at 1 mM, in DMSO at 100 mM
- High diversity within each bioisosteric type
- No reactive or unstable compounds, pains free
- Analogs from stock and REAL Space available for each fragment
Examples of compounds in the library
Library design
Analysis of the existing literature combined with internal experience at the ICR allowed us to choose more than thirty CAB substructure types. We identified over 40,000 compounds containing CAB moieties in our stock. Some underrepresented classes were identified, and new compounds were synthesized to fill these gaps. Compounds containing carboxylic acid groups or highly reactive groups were filtered out. A slightly relaxed version of the Rule of Three (Ro3) was applied along with diversity selection to comply with the standard practices of fragment-based library design while allowing some flexibility to enhance library size and diversity. We further extended the selection to compounds whose properties are in line with those of functionally diverse fragments that perform best in fragment screens (Deane et al., J. Med. Chem. 2022, 65, 11404−11413). The final selection contains only compounds that passed nephelometry-based solubility threshold studies (solubility in DMSO at 100mM and 1mM in PBS at pH 7.4). The library composition was visually checked by Enamine and ICR experts to remove trivial and MedChem unfriendly compounds. The distribution of CAB classes took into account both medicinal chemistry attractiveness and synthetic tractability, the latter being crucial for the hit follow-up stage. Tetrazoles and N-acyl sulfonamides are the most abundant classes in the library followed by 1,2,4-oxadiazoles, 3-sulfonyl-1,2,4-triazoles, hydroxamic acids, oxetane-3-ols, 3-hydroxypyrazoles and others with 20 CAB classes in total.
Molecular properties
New chemical space for discovery
REAL® Compounds are an extension to our stock Screening Collection. They are REadily AccessibLe through validated parallel synthesis using our in-stock building blocks. Ordering REAL Compounds is as easy as if they were available from stock.
Some applications include:
- Hit exploration
- Compound collection enhancement
- AI-based lead discovery
- Ultra-large virtual screening
Quick facts
- Over 94.5B novel compounds for cherry-picking
- Ship from 3 weeks
- Over 80% compounds delivered
How to access
- REAL Database. This is a database of currently 13.6B enumerated compounds, which is publicly available and free to download.
- REAL Space. A convenient chemoinformatics tool operated with infiniSee developed by BioSolveIT generates REAL Compounds on the fly. REAL Space compounds have also been enumerated in a separate effort. This database is provided on request.
- xREAL Space. 2.4 trillion molecules! This Space is available through infiniSee xREAL developed by BioSolveIT. Also available through Chemspace via their Discovery Services.
- REAL Database Subsets. A practical way to start exploring REAL Database.
- Online search. You can conveniently search for REAL Compounds using substructure and similarity queries on EnamineStore.com providing access to the entire REAL Database.
Novelty
REAL Compounds are a next generation screening compound collection that allows reaching billions of previously unknown structures. Enamine continuously develops new and innovative building blocks. These building blocks provide access to enumerated libraries of novel REAL Compounds. In most cases, Enamine provides an option of supplying these compounds without publishing them in its stock catalogues and SciFinder.
Diversity
REAL Database has over 14 million Bemis-Murcko frameworks (BMF’s). We achieved this enormous variety of frameworks with 137 000 building blocks used in 167 synthetic protocols. A diversity subset of REAL Database is available here.
Drug-likeness
Ro5 and Veber's rule compliant:
- MW ≤500
- SlogP ≤ 5
- HBA ≤ 10
- HBD ≤ 5
- RotBonds ≤ 10
- TPSA ≤ 140
Prices
All REAL Compounds have flat prices. They come from two categories.
-
s-REAL Compounds are synthesized via standard 1-2 step procedures with 80%+ success rate.m-REAL Compounds are 50% more expensive than s-REAL Compounds because their synthesis involves either multistep synthesis procedures, or use of expensive building blocks, or the products require special purification.
Ideas for a quick start
-
Diversity set. You can make a plot screen of REAL Compounds using a diverse subset from REAL DatabaseDownload infiniSee and run search within 94.5B compounds on an ordinary computerOnline search. You can conveniently search for REAL Compounds on EnamineStore.com providing access to the entire REAL Database.
Yes, REAL Compounds are not in stock, but...
- All building blocks available in OUR stock
- Each building block has already been tested to comply with synthesis procedure
- We know in advance which of the synthesis protocols developed in-house to use
...we deliver as if the compounds were available from stock
Publications that cite Enamine REAL
- SpaceGrow: efficient shape-based virtual screening of billion-sized combinatorial fragment spaces J Comput Aided Mol Des 2024, 38 (1), 13. DOI: 10.1007/s10822-024-00551-7
- The HZB F2X-Facility—An Efficient Crystallographic Fragment Screening Platform Applied Research 2024, in press. DOI: 10.1002/appl.202400110
- Navigating Chemical Space Computational Drug Discovery: Methods and Applications 2024, 337-363. URL: 10.1002/9783527840748.ch15
- Generative artificial intelligence for small molecule drug design Curr Opin Biotechnol 2024, 89, 103175. DOI: 10.1016/j.copbio.2024.103175
Enamine is a reliable partner for compound collection enhancement (CCE) programs providing a full cycle of services from development of the initial concept in close collaboration with customer and synthesis of the scaffolds to parallel chemistry and compound management of the library compounds.
We offer:
- Business model adaptable for each customer – fee-for-service, FTE-based or mixed.
- Flexible design – based on the customer’s template(s) or our own scaffold collection, or focused on special compound classes such as covalent ligands or macrocycles. We can reshape the compound collection using advanced chemoinformatics tools according to virtually any selection criteria.
- Diversity and speed – we can rely on the world’s largest collection of stock Building Blocks (around 200K) to construct the target cores and to decorate them.
- Experience – we are highly skilled in both parallel chemistry and complex multistep synthetic projects, with >2 000 customers varying from small biotech and academia to big pharma.
- Quality control and logistics – we perform reversed-phase preparative HPLC purification on all synthesized compounds to assure they meet purity requirements (usually 90% or 95% pure). Their quality is controlled with LCMS and up to 100% with 1H NMR. The compounds can be delivered in virtually any containers, including those received from a customer and assay-ready plates for immediate screening.
Please contact us at
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