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ASINEX - Inspired by Nature Alkaliod-like Library
 
ASINEX - Inspired by Nature Terpenoid-based Library
 
ASINEX - Inspired by Nature Glycomimetic Library
 
ASINEX - Inspired by Nature Macrocyclic Library
 
 
 
Home > Libraries > Minimalist Libraries
 
Minimalist Libraries
 

ASINEX's Minimalist Libraries 2011
17000 compounds / 125 scaffolds

High Skeletal Diversity Inspired by Nature

ASINEX continues to develop a compendium of natural product-like libraries by incorporating structural features of pharmacologically relevant natural products into the scaffold skeletons of synthetic compounds. In order to identify privileged pharmacophores, ring systems and linkers, we have carried out a statistical analysis of natural product alkaloids, marketed drugs and commercial libraries. It was found that saturated linked, fused, spiro and bridged ring systems, with a tendency towards chirality, are highly privileged among natural products and marketed drugs, but at the same time are poorly represented in commercial libraries.

This data is consistent with the synthetic accessibility of such structural elements and clearly indicate areas of high chemical complexity where traditional methods of combinatorial chemistry are barely applicable. In order to address these challenging areas ASINEX's chemists have focused their attention on more sophisticated stereo-controlled reactions and biomimetic transformations such as

  • Epoxide tandem transformations
  • Olefin transformations
  • Asymmetric rearrangements

The applied synthetic strategy provided the compounds with:

  • Exceptionally high shape and stereochemical complexity [1]
  • Increased number of minimalist pharmacophoric elements [2]
  • A high number of O-atoms per molecule

These are characteristic features differentiating natural products from "common" synthetic molecules.

The skeletal diversity is represented by fused, spiro, bridged and macrocylic (rings with > 8 atoms) frameworks. In many cases the position of heteroatoms and functional groups within the framework emulates the corresponding molecular pattern of marine toxins, carbohydrates and alkaloids.

Unlike typical DOS-derived molecules, Biomimetic compounds do not contain undesirable functionalities and are optimized in terms of physico-chemical parameters. Moreover, the Biomimetic library is supported by a special collection of advanced intermediates and building blocks available in multi-gram quantities. The final compounds with MW<275 Da represent a very valuable source of unique, three-dimensional, fragment-like molecules which have been specifically refined and tested for solubility in aqueous media.

The Biomimetic Library provides a very rich source of original peptidomimetic scaffolds and is ideal for probing challenging target classes including:

  • Protein-protein interactions
  • Proteases
  • Ion Channels
  • Antibacterial / antiviral targets

Library specifics
Quality: min.purity of 90%, avg. of 95% (LC-MS, NMR), stored as dry powder

For more information please contact ASINEX at:
Tel.: +7 (495) 780 34 15, +7 (495) 780 34 10
E-mail : LSadovenko@asinex.com or Busdev@asinex.com


1. Paul A. Clemons, et al. Small molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles PNAS , November 2, 2010 , vol. 107 , no. 44, 18787-187922.
2. Gilbert M Rishton, Molecular diversity in context of leadlikeness: compound properties that enable effective biochemical screening, Curr Opin Chem Biol 2008, 12: 1-12.

 
Terpenoid-based Library
 

ASINEX's Cyclic Polyether Library
3000 compounds / 45 scaffolds

Unprecedented Diversity of Oxygen-enriched Scaffolds through Biomimetic Synthesis

It is increasingly recognized that an overwhelming structural diversity of marine natural products provides a very rich source of inspiration for medicinal chemists, helping them to design new drugs for the treatment of challenging human diseases [1]. Specifically, several marine toxins with polyether pharmacophores have found their application as promising anticancer or anti-infective agents [1,2]. It is believed that small drug-like molecules containing a similar distribution of oxygen atoms within a polycyclic framework may demonstrate similar biological effects to their natural product prototypes, but with a greater efficacy and specificity to a certain molecular target [3,4].

ASINEX has developed a synthetic toolbox which has enabled us to generate a unique library of skeletally diverse (saturated fused-, spiro- systems) highly oxygen rich molecules. The synthetic strategy is based on biomimetic transformations of natural products, such as NOPOL, NEROL and GERANIOL, into novel polyether derivatives. These cyclic molecules contain several versatile functionalities (OH, NH, COOH) which are amenable to further medicinal chemistry exploration. The final compounds can be achieved in 5-9 steps using a cascade of reactions with high enantio- and/or diastereoselectivity, including the regioselective olefin alkylation, the Shi epoxidation and the tandem epoxide opening-cyclization. The stereochemistry of all key intermediates has been confirmed by X-ray crystallography and 2D-NMR. These intermediates are available for follow-up chemistry in gram quantities.



Library specifics
High content of chiral compounds: 70% of a total set
Structure identity confirmed by NMR, X-ray crystallography
Measured Solubility: 100% of compounds are soluble in DMSO at 10 mM, and in PBS at 50 µM
Quality: min.purity of 90%, avg. of 95% (LC-MS, NMR), stored as dry powder

ASINEX's Cyclic Polyether Library is only available upon request, please contact us at:
Tel.: +7 (495) 780 34 15, +7 (495) 780 34 10
E-mail : LSadovenko@asinex.com or Busdev@asinex.com


1. Tadeusz F. Molinski et al., Drug development from marine natural products, Nature Reviews Drug Discovery, 2009, 8, pp 99-85.
2. Adam Huczynski et al., Synthesis and antimicrobial properties of Monensin A esters, Bioorganic & Medicinal Chemistry Letters, V. 18, Issue 8, 2008, pp 2585-2589.
3. Hiroki Oguri et al., Design and synthesis of a trans-fused polycyclic ether skeleton as an alfa-helix mimetic scaffold, Tetrahedron Letters 46, 2005, pp 2179-2183.
4. Torikai K et al.,Design and Synthesis of Ladder-Shaped Tetracyclic, Heptacyclic, and Decacyclic Ethers and Evaluation of the Interaction with Transmembrane Proteins, JACS, 2008, 130, pp 10217-10226.

 
 
Glycomimetic Library
 

ASINEX's Glycomimetic Library

High pharmacophore density of sugar-like compounds

Carbohydrates and carbohydrate-like molecules represent a particularly intriguing part of chemical space, due to their pivotal role in regulating many biological processes and providing valuable chemical starting points for the design of novel small-molecule drugs [1]. Cyclic amino alcohols and cyclic glycols are the common structural features of carbohydrates and other natural products. They constitute very important protein recognition pharmacophores exploited in industry for the design of new drugs (e.g. anti-infective agents) and as "chemical chaperones" [2]. However due to the presence of several stereogenic centers, high polarity and high saturation, the synthetic feasibility of such compounds represent additional hurdles for medicinal chemists. It is not surprising that such highly valuable chemotypes are under-represented in commercial compound collections.

In order to address this challenge ASINEX has designed a special library of 2700 novel carbohydrate-like compounds enriched with poly OH(NH) pharmacophores. Our synthetic expertise enabled us to produce compounds as single diastereoisomers, with the structures confirmed by both 2D NMR and X-ray crystallography. All final compounds demonstrate exceptionally good solubility in aqueous media and are chemically stable which makes them ideal for screening in multiple applications:

  • Protein-protein interactions
  • Proteases
  • Antiviral/antibacterial targets

Additionally, 700 compounds with MW < 250 represent a very valuable source of unique fragment-like molecules which have been specifically refined and tested for solubility in aqueous media. These compounds are available for purchasing in larger quantities (up to 100 mg).



Library specifics
Measured Solubility: 100% of compounds are soluble in DMSO at 10 uM, and in PBS at 100 µM
Quality: min.purity of 90%, avg. of 95% (100% LC-MS, 15% NMR), stored as dry powder

ASINEX's Glycomimetic Library is only available upon request, please contact us at:
Tel.: +7 (495) 780 34 15, +7 (495) 780 34 10
E-mail : LSadovenko@asinex.com or Busdev@asinex.com


1. Beat Ernst, John L. Magnani. From carbohydrate leads to glycomimetic drugs, Nature Reviews Drug Discovery 8, August 2009, pp 661-677.
2. Zhanqian Yu, et al. Isofagomine- and 2,5-Anhydro-2,5-imino-d-glucitol-Based Glucocerebrosidase Pharmacological Chaperones for Gaucher Disease Intervention, J. Med. Chem., 2007, 50 (1), pp 94-100.

 
Macrocyclic Library
 

ASINEX's Macrocyclic Compound Library

Under-represented structural class in screening collections

Mid-sized and large-sized ring compounds have always been considered by medicinal chemists as a stand-alone class of molecules, not only due to their interesting physico-chemical and biological properties, but also due to the challenge of their synthesis [1]. To address this issue, ASINEX has elaborated a medchem library of 5000 compounds in which a peptidomimetic macrocycle ring is attached to a privileged pharmacophore - piperidine, pyrrolidine etc. The resulting combination is novel and allows the generation of a tremendous diversity of medchem-relevant macrocyclic frameworks. The presence of intrinsic points of diversity allows for the introduction of additional pharmacophores into the periphery, which have been selected based on the analysis of known drugs and natural products.

Considering that macrocylic molecules tend to be larger and more lipohilic than traditional screening molecules, it is vital to control their physico-chemical properties in advance. Therefore all macrocyclic molecules have been tested for aqueous and DMSO solubility with the cut-offs of 10 mM in DMSO and 100 µM in PBS (pH 7.4). The synthesis strategy is based on ASINEX's expertise in olefin transformations and catalytic cyclizations.

Due to a restricted conformational flexibility and a favorable orientation of the exiting peripheral substituents, some of the macrocyclic compounds can effectively mimic the alpha helical or beta strand/sheet topology of some biologically relevant proteins.

The Macrocyclic Compound Library provides a very rich source of peptidomimetics and is ideal for probing challenging target classes including:

  • Protein-protein interactions
  • Antibacterial / antiviral targets

Library specifics
Measured Solubility: 100% of compounds are soluble in DMSO at 10 mM, and in PBS at 100 µM
Quality: min.purity of 90%, avg. of 95% (LC-MS, NMR), stored as dry powder

ASINEX's Macrocyclic Compound Library is only available upon request, please contact us at:
Tel.: +7 (495) 780 34 15, +7 (495) 780 34 10
E-mail : LSadovenko@asinex.com or Busdev@asinex.com


1. Lisa A. Marcaurelle et al. An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors, J. Am. Chem. Soc., 2010, 132 (47), pp 16962-16976.

 
Alkaliod-like Library
 

ASINEX's Alkaliod-like Library
13975 compounds/ 115 scaffolds

Under-represented structural classes in screening collections

It is now well-accepted that compact molecules with multiple minimalist pharmacophore fragments which are common for both natural products and drugs could be beneficial in small molecule lead generation programs [1]. Synthetic screening libraries containing such molecules are highly desirable in medicinal chemistry as they are associated with increased protein binding properties [2]. Incorporation of such elements into conformationally constrained saturated cyclic scaffolds leads to molecules of sophisticated 3D architecture containing multiple stereogenic centers.

Medicinal chemists are particularly interested in libraries where saturation and 3D complexity are attributed to the nature of the molecular scaffold core rather than peripheral appendages [3]. This provides an additional challenge for synthetic chemists as it implies an extensive usage of regio-, stereo- and enantioselective reactions. At ASINEX, we deliberately exploit the advantages of modern stereo-controlled transformations to create novel saturated poly-N,O fused-, spiro-ring systems. The resulting molecular scaffolds are properly functionalized and amenable for generating focused compound arrays. ASINEX supports further follow up optimization by providing corresponding synthetic protocols and intermediates.

The final compounds with MW<275 Da represent a very valuable source of unique, three-dimensional, fragment-like molecules which have been specifically refined and tested for solubility in aqueous media.

ASINEX's Minimalist Compound Library is only available upon request, please contact us at:
Tel.: +7 (495) 780 34 15, +7 (495) 780 34 17
E-mail : LSadovenko@asinex.com or Busdev@asinex.com

 
 
 
 
 
 
 
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