Loading ePaper
Life Science Core Structures for Medicinal Chemistry OOOO
Gute Chemie. Connects. Your abcr Team
Gute Chemie. Foreword 1 Gute Chemie. Welcome to abcr. What do you think of when you hear the expression ‚Gute Chemie‘? Does it make you think of top-quality products or people that understand each other really well? Since we set up our company in 1987, we have consistently attempted to combine both. We offer Gute Chemie in the form of more than 300,000 specialty chemicals that we supply to major pharmaceuticals and chemical companies. And we also provide Gute Chemie in terms of our personal service coupled with an extensive network that links our clients, suppliers and partners all around the world. With this brochure, we would like to invite you to experience all the aspects of Gute Chemie. Dr. Jan Schuricht | Managing Director
The company. Gute Chemie comes from abcr. abcr GmbH Germany abcr Locations Worldwide
In-house production. Gute Chemie means trusting in the quality. abcr has a strong focus in developing and providing new products for Life Science and related disciplines. Our catalogue incoporates more than 6,000 unique products from reliable sources. 6,000 products - still not in the portfolio? With our R&D Service and Global Sourcing we aim on novel unknown compounds with special strength in organic and medicinal chemistry. abcr R&D Services - your partner for ¡ Process development and optimization ¡ Product development ¡ Elaboration of described synthesis pathways ¡ Establishment of new routes for novel and unique compounds ¡ Feasibility studies ¡ Scale-up and toll manufacturing from gram to kilo
OOOO
Core Structures for Medicinal Chemistry. Table of contents. Phenyl Bioisosteres Bicyclo[1.1.1]pentanes Bicyclo[2.2.2]octanes Cubanes Boronic Acids and Derivatives Quinolinyl Boronic Acids Isoquinolinyl Boronic Acids Indazolyl Boronic Acids Dioxaborinane Heteroboroles 6 8 10 12 14 16 18 20
6 Phenyl Bioisosteres Bicyclo[1.1.1]pentanes Substituents F, Cl, Br, I CN, CHO, COOH, COOMe NH2, CF3 and other derivatives Further variations on request at sales@abcr.de References [1] Stepan, A. F. et al. Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active gamma-secretase inhibitor. Journal of medicinal chemistry 55, 3414-3424, doi:10.1021/jm300094u (2012). [2] Auberson, Y. P. et al. Improving Nonspecific Binding and Solubility: Bicycloalkyl Groups and Cubanes as para-Phenyl Bioisosteres. ChemMedChem 12, 590-598, doi:10.1002/cmdc.201700082 (2017). Gute Chemie
Gute Chemie. Phenyl Bioisosteres 7 O OH HO AB459079 AB471891 AB486332 O OH F F F O OH O OH Cl NBoc AB486761 AB486870 AB490899 O OH H2N OH O Br Br AB494671 AB471905 AB471920 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
8 Phenyl Bioisosteres Bicyclo[2.2.2]octanes Substituents CN, CHO, COOH, COOMe NH2, NBoc F, Br, OH Alkyls, Aryls and other derivatives Further variations on request at sales@abcr.de References [1] Watanabe, Y. et al. Design and synthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton having a 7-amide side chain and their pharmacologies. Bioorg Med Chem 21, 3032- 3050, doi:10.1016/j.bmc.2013.03.026 (2013). [2] Auberson, Y. P. et al. Improving Nonspecific Binding and Solubility: Bicycloalkyl Groups and Cubanes as para-Phenyl Bioisosteres. ChemMed- Chem 12, 590-598, doi:10.1002/cmdc.201700082 (2017). Gute Chemie
Gute Chemie. Phenyl Bioisosteres 9 O OH NH H2N HCl O OH AB400847 AB435673 AB458753 O O H2N HCl NBoc HO AB402388 AB440018 AB463576 Br OH O O O OH H2N NBoc AB480014 AB492425 AB490100 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
10 Phenyl Bioisosteres Cubanes Substituents Cl, Br, I COOH, COOMe CH2OH, OH and other derivatives Further variations on request at sales@abcr.de References [1] Chalmers, B. A. et al. Validating Eaton‘s Hypothesis: Cubane as a Benzene Bioisostere. Angew Chem Int Ed Engl 55, 3580-3585, doi:10.1002/anie.201510675 (2016). [2] Auberson, Y. P. et al. Improving Nonspecific Binding and Solubility: Bicycloalkyl Groups and Cubanes as para-Phenyl Bioisosteres. ChemMedChem 12, 590-598, doi:10.1002/cmdc.201700082 (2017). Gute Chemie
Gute Chemie. Phenyl Bioisosteres 11 O OH O O O O HO O O O HO AB175524 AB175451 AB175527 OH HO O N O O N O HO O AB470868 AB470869 AB175525 O O O O Cl I H2N HCl AB175533 AB425654 AB175549 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
12 Boronic Acids and Derivatives Quinolinyl Boronic Acids Substituents B(OH)2 BF3K, pinacol ester F, Cl, Br CHO, COOMe Me, OMe, Ph CF3, OCF3, NO2 and other derivatives Further variations on request at sales@abcr.de References Rikita, T., Egawa, Y. & Seki, T. Fluorometric determination of inulin using 5-quinolineboronic acid and inulinase. Anal Biochem 426, 24-26, doi:10.1016/j.ab.2012.03.029 (2012). Gute Chemie N
Gute Chemie. Boronic Acids and Derivatives 13 OH N B OH OH B OH N HO OH B N AB246613 AB175446 AB172666 HO OH B OH B HO N N HO B OH N AB466713 AB466591 AB467229 N B HO OH AB466090 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
14 Boronic Acids and Derivatives Isoquinolinyl Boronic Acids Substituents B(OH)2, BF3K, pinacol ester Substituents Cl, OMe Further variations on request at sales@abcr.de References Ni, N. et al. Probing the general time scale question of boronic acid binding with sugars in aqueous solution at physiological pH. Bioorg Med Chem 20, 2957-2961, doi:10.1016/j. bmc.2012.03.014 (2012). Gute Chemie N
Gute Chemie. Boronic Acids and Derivatives 15 HO OH B N Cl AB446181 OH B HO N N HO OH B HO OH B N AB468149 AB466145 HO N B OH B HO OH AB261480 AB463180 AB446182 N Cl O OH B HO OH B HO Cl N O N HO N B OH AB446184 AB446172 AB446173 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
16 Boronic Acids and Derivatives Indazolyl Boronic Acids Substituents CF3 COOH, COOMe Substituents Alkyl NH2 Further variations on request at sales@abcr.de References Das, B. C. et al. Boron chemicals in diagnosis and therapeutics. Future medicinal chemistry 5, 653-676, doi:10.4155/fmc.13.38 (2013). Gute Chemie NN
Gute Chemie. Boronic Acids and Derivatives 17 HO B OH N N H HO B OH N N H HO B OH N N O AB465894 AB467017 AB446163 HO B OH N N H N N HO B OH N N B HO OH AB467070 AB271894 AB466456 OH B HO N N OH B HO N N H HO OH B N N H AB466454 AB467068 AB467064 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
18 Boronic Acids and Derivatives Dioxaborinane Substituents OR, CH2R NH2, I and other derivatives Further variations on request at sales@abcr.de References Das, B. C. et al. Boron chemicals in diagnosis and therapeutics. Future medicinal chemistry 5, 653-676, doi:10.4155/fmc.13.38 (2013). Gute Chemie OBO
Gute Chemie. Boronic Acids and Derivatives 19 O B O I B O O O BocN B O O O NBoc AB497037 AB168200 AB168202 B O O O NBoc B O O N BocN B O O N NBoc AB168203 AB168192 AB168206 HN B O O Cl B O O H2N HCl B O O Br AB491582 AB352053 AB347799 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
20 Boronic Acids and Derivatives Heteroboroles Substituents F, Cl, Br, I NH2 NO2 CF3 Me OR and other derivatives Further variations on request at sales@abcr.de References [1] Jay, J. I. et al. Multivalent benzoboroxole functionalized polymers as gp120 glycan targeted microbicide entry inhibitors. Molecular pharmaceutics 7, 116-129, doi:10.1021/mp900159n (2010). [2] Das, B. C. et al. Boron chemicals in diagnosis and therapeutics. Future medicinal chemistry 5, 653-676, doi:10.4155/fmc.13.38 (2013). Gute Chemie OBOH
Gute Chemie. Boronic Acids and Derivatives 21 OH B O OH B O F F F H2N HCl OH B O AB146919 AB271430 AB150491 O- N+ O OH B O OH B O N OH B O F O AB150641 AB442579 AB440011 OH B O H2N O2N OH B O OH B O HO AB504778 AB487469 AB485826 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
22 Product line Life Science 01 New Chirals for Drug Design Special chemicals require special knowledge. Rely on abcr‘s competence. Talk to our experts, we will give you plenty of friendly advice and guide you through the whole process. This comprehensive service is already valued by well-known customers from the life science, pharmaceutical & medical industry. abcr offers a wide range of compounds for the MedChem. Find further products for various applications in the field of drug design in our brochure Life Science 01 – see the overview below: Disubstituted Naphthaline Derivatives 1,7- Disubstituted Naphthaline Derivatives O OH NH2 NH2 (R) (R) NH2 (S) (S) R R R R R Chromanones and Aminochromanes 4,6-disubstituted chromane derivatives 4,8-disubstituted chromane derivatives R O O R NH2 O R R NH2 (R) (R) O NH2 (S) (S) O O O R NH2 O R NH2 (R) (R) O NH2 (S) (S) O R R Gute Chemie
Gute Chemie. Life Science 01 – New Chirals for Drug Design 23 Indanones and Aminoindanes Synthesis of 1-Aminoindane derivatives Synthesis of indanyl derived amino acids O NH2 R R R R NH2 (R) (R) NH2 (S) (S) O R OH O R NH2 O R OH NH2 (R) (R) O R OH NH2 (S) (S) Diaminocyclohexane (DACH) Derivatives Unsubstituted, N-monosubstituted, and N,N‘-disubstituted DACH compounds N,N,N‘,N‘-Tetrasubstituted DACH compounds: R NH NH R R NH NH R R1 N R2 R1 N R2 (R,R) R1 N R2 R1 N R2 (S,S) Chiral Alcohols Trifluoromethyl substituted aliphatic alcohols Phenyl substituted aliphatic alcohols OH R F F F OH OH F F F R F F F R OH OH R1 R2 R3 R4 R1 R2 R3 R4 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ sales@abcr.de ▪ www.abcr.de
24 Gute Chemie. Notes Gute Chemie
Publishing details abcr GmbH Im Schlehert 10 76187 Karlsruhe Germany Phone +49 721 95061 - 0 Fax +49 721 950610 - 80 info@abcr.de ▪ www.abcr.de Registered office Karlsruhe Managing Director Dr. Jan Schuricht District court AG Mannheim HRB 104793 Tax number 35005/14749 VAT number DE 815518524 DUNS number 320054844 Publisher: abcr GmbH 478584.0817.3 © abcr - All rights reserved.
Gute Chemie. Greater diversity, choice and value. Make use of our e-papers to quickly and easily browse through our catalogues and flyers and search for products. All products listed in the e-papers are linked to the respective product detail page within our website where you will find further information. We can also send the catalogues and flyers by mail. Life Science Drug Design Silicon Compounds Organozinc Reagents Palladium Catalysts Fluorinated Compounds Catalysts Ligands Fluorinated Isoquinolin Glove Bag Accessoires Kit Find 300,000 specialty chemicals in our webshop: www.abcr.de abcr GmbH Germany +49 721 95061-0 info@abcr.de abcr swiss AG +41 41 7201882 info@abcr-swiss.ch abcr IRL Ltd. +353 56 7738971 info@abcr-irl.ie abcr france SAS +33 4 7291 3100 info@abcr-france.fr abcr Chemie Rus, LLC +7 495 966-41-81 abcr-russia@abcr.de Palladium catalysts for C-C and C-N coupling reactions01Palladium catalysts for C-C and C-N coupling reactions01Commercial Organofunctional Silanes for Diagnostics and Separation01Commercial Organofunctional Silanes for Diagnostics and Separation0101Available in bulk quantities Fluoro Organic Intermediates01Available in bulk quantities Fluoro Organic IntermediatesNew Organozinc Reagents for Organic Synthesis01New Organozinc Reagents for Organic Synthesis01(R,R)-Catalyst (35 mol-%)MnO2 (3 eq.), Li2CO3 (2 eq.)PhCF3, 115 °C, 24 hup to 86% yield) (2 eq.)NNOSO2RHHNNHSO2Rup to 94% yield(S,S)-ligand (8 mol-%)THF, diglyme-20°CRalkylNN (6 mol-%)(S,S)-ligand (8 mol-%)R1CF3R1+F3C(S,S)-ligand (8 mol-%THF, diglyme-20°CalkylCoI2 (10 mol-%)(S,S)-ligand (12 mol-%)THF, -80°CArylMgBrROup to 96% yield)ROArylalkylCoI(S,S)-ligand (12 mol-%THF, -80°CROBralkyl+ArylMgBrup to 96% yieldONNOCuTfOOTfNNO(R,R)-Catalyst (35 mol-%)MnO2 (3 eq.), Li2CO3 (2 eq.)PhCF3, 115 °C, 24 hup to 86% yield) (2 eq.)NNOSO2RHHNNHSO2RR2(DME)NiCl2 (5 mol-%)(S,S)-ligand (6 mol-%)TMEDA (1.6 eq.)THF, 0°Cup to 94% yieldR1 (5 mol-%) (6 mol-%)R1FFNOR2R2ZnClR1+BrFFNOR2R2(DME)NiCl(S,S)-ligandTMEDA (1.6 eq.)THF, 0°Cup to 94% yield(DME)NiCl2 (6 mol-%)(S,S)-ligand (8 mol-%)THF, diglyme-20°CRalkylONNO (6 mol-%)(S,S)-ligand (8 mol-%)R1alkylCF3ZnClR1+F3C(DME)NiCl(S,S)-ligand (8 mol-%THF, diglyme-20°CXalkylCoI2 (10 mol-%)(S,S)-ligand (12 mol-%)THF, -80°CArylMgBrROup to 96% yield)ROArylalkylCoI(S,S)-ligand (12 mol-%THF, -80°CROBralkyl+ArylMgBrup to 96% yieldNNO(S,S)-ligandONNOCuTfOOTfNNOISO9001:2008DINENISO9001NOR3HR1R2R4HGlove Bag –Einfach sicherLife ScienceNew Chirals for Drug DesignNNNN01Life ScienceNew Chirals for Drug DesignNNNN01