Building Blocks Catalog

284 Thousand compounds in stock

Original and unique

Make-on-demand
Building Blocks

210 Million novel building blocks

Reliable supply

Custom Synthesis

Over 650 highly skillful chemists

Unique synthesis technologies

Library Synthesis

31B Billion REAL compounds and

Custom Library Synthesis

FTE Chemistry Support

On site access to all Enamine stock BB’s

Highly flexible arrangements

2 000 new building blocks are synthesized monthly. Here is an important update to our MedChem Highlights from October 2022

Recent News

Upcoming events

Cereblon ligands and functionalized intermediates

CRBN binders and their functionalized analogs

Cereblon (CRBN) is one of the most explored E3 ligase used for the construction of PROTACs and different functionalized tool compounds. The most extensive research has been done in this area. We have also been working on thalidomide-like and glutarimide chemistry for years and gained versatile experience in this chemistry field. New Building Blocks have been synthesized along with extensively elaborated approaches in modification of common intermediates. This knowledge allowed as to create over 500 000 REAL CRBN focused compounds based on a range of synthesized in-stock intermediates.

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Building Blocks for parallel chemistry

  • CRBN Building Blocks in stock – over 200 intermediates
  • CRBN MADE Building Blocks – 10 000+ compounds
  • CRBN MADE Building Blocks with linkers – over 80 000 compounds

CRBN focused products

  • Thalidomide-like, and other celebron ligands and ligands with linkers in-stock – 5 500
  • Glutarimides in stock – over 3 000 compounds
  • CRBN binders – pre-plated 320 compounds
  • REAL Molecular Glues – 3.5 M compounds
  • Custom CRBN ligands and ligands with linkers
  • REAL CRBN ligands with covalent warheads

Representative examples of CRBN binders with varying linkers

SPLicing inhibitor sulfonAMides (SPLAMs)

New aryl sulfonamides designed to target DCAF family of E3 ligases

For a long time, Indisulam and a few other clinically tested aryl sulfonamides such as Tasisulam and chloroquinoxaline sulfonamide (CQS) remained compounds with pronounced selective in vitro anticancer activity with unclear mechanism of action.

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Recent extensive investigations in cancer genome sequencing together with X-Ray crystallography and cryo-electron microscopy showed that these compounds (also known as SPLAMs - SPLicing inhibitor sulfonAMides) act as a “molecular glue” to induce degradation via binding to DCAF15. This insight provided structural and mechanistic data that significantly extend our understanding of their mode of action.

E7820

Indisulam

Tasisulam

CQS

Based on these emerging data we have designed several focused compound libraries of aryl sulfonamides both using selections from our Screening Collection and employing enumerations of new REAL compounds that we can confidently synthesize:

Library design

Recent studies demonstrated that SPLAMs promote the interaction between RBM39 and DCAF15 E3 ligase receptor, leading to ubiquitination of RBM39 and proteasome-mediated degradation.

According to the structural data Indisulam and Tasisulam bind DCAF15 in an overall configuration similar to E7820, maintaining the backbone hydrogen bonds from the sulfonyl groups to DCAF15 Ala234 and Phe235 and the water mediated hydrogen bonds. However, the methyl to hydrogen substitution at C4 in Indisulam limits the hydrophobic interactions with DCAF15 Val477 and Val556, while Tasisulam lacks the indole NH hydrogen bond to the backbone carbonyl of DCAF15 Phe231.

Based on the available structural data we have designed DCAF15 Focused Library from our stock Screening Collection using the following approach:

  • Generation and selection of close chemotypes/scaffolds based on diverse aryl and heteroaryl (five-membered inclusive) sulfonamides;
  • Further selection based on pharmacophore modelling and docking results using available structural data of DCAF15;
  • MedChem filtering according to criteria of lead/drug likeness.
Docking results

Figure 1. Docking results

Figure 2. Examples of SPLAM analogues

Protein Degradation Toolbox

Out-of-the-box tools for your research in PD

One of the most emerging therapeutics area focused on modulating the ubiquitin proteasome system is in dire need of new and reliable chemistry. Booming biological assays in this field of drug discovery require production of hundreds and thousands of new functional intermediates and bifunctional molecules. The time needed for production of new derivatives is crucial for any new project in this therapeutic area. We offer advanced synthetic chemistry support including custom library design and synthesis.

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To facilitate all further work on bifunctional molecules we constantly update our toolbox with newly synthesized intermediates and functionalized ligands. The actively developing area of Molecular Glues keeps us highly motivated to synthesize new Building Blocks and intermediates.

We offer distinct tools that you can mix-up to design molecules of your special interest. The following options are available for synthesis of new molecules or immediate delivery to your research site:

Cereblon ligands and functionalized intermediates
VHL ligands and ligands with linkers
Orthogonal Linkers
Molecular Glues
Functionalized Warhead Ligands
Active Degraders
Halo- & Photo- Capture Tags
SPLicing inhibitor sulfonAMides

Chloroacetamides

The world’s largest collection

4 861 compounds

Amides of chloroacetic acids are soft alkylating agents and are among the most popular covalent binders. They are synthesized using amide coupling reaction of chloroacetic acids with primary and secondary amines:

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Besides cherry-picking from around 2 000 chloroacetamides from stock you can acquire a small library of these covalent ligands already plated in DMSO solution for fast supply. Conducted stability tests show that compounds remain in frozen DMSO solution at least within 1 year without any significant degradation.

Chloropropianates. Somewhat less reactive amides of α-chloropropionic acid can be also employed in discovery of selective covalent probes.

Synthesis of new covalent ligands. We offer a unique possibility to produce a customized library of chloroacetamides and / or chloropropianates. Based on our experience in making these covalent compounds and availability of over 40k amines in our stock we have enumerated a library of REAL (readily accessible) covalent compounds. We will produce at least 80% compounds from your selection within only 4-6.

Covalent Compounds

The largest and most reliable source of novel covalent modifiers

95 908 compounds

Covalent screening has become an integral part of Drug Discovery process and is now playing an essential role in hit finding, development of novel screening techniques, identification of new protein targets and assessment of their drugability. Successful drug development campaigns featuring a transition to the covalent binder solidify covalent compounds as a powerful tools for drug design.

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In spite of high interest within last few years, the number of commercially accessible covalent binders remains extremely limited, with poor structural diversity and low attractiveness of core structures.

To create a reliable source of covalent modifiers Enamine has focused on elaboration of parallel synthesis approaches to synthesize series of new valuable covalent compounds. Careful choice of appropriately reactive building blocks, optimization of the reaction conditions and elaboration of HPLC purification methods have already allowed synthesis of thousands of different covalent binders and resulted in enumeration of REAL arrays – new readily accessible covalent compounds that can be confidently synthesized within 4 weeks only.

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