- Fragment-based design of selective GPCR ligands guided by free energy simulations
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Fragment-based drug discovery relies on successful optimization of weakly binding ligands for affinity and selectivity. Herein, we explored strategies for structure-based evolution of fragments binding to a G protein-coupled receptor. Molecular dynamics s
- Matricon, Pierre,Vo, Duc Duy,Gao, Zhan-Guo,Kihlberg, Jan,Jacobson, Kenneth A.,Carlsson, Jens
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supporting information
p. 12305 - 12308
(2021/12/07)
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- Synthesis of sulfur heterocycles via domino metal-mediated reactions
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Two methodologies to access S-heterocycles and mixed N,S-heterocycles via metal-mediated domino reactions are described. One involves a cyclocarbopalladation/cross-coupling domino process and leads to benzene-fused five- or six-membered sulfur heterocycles with a stereo defined tetrasubstituted exocyclic double bond. The other consists in a three-component domino reaction between 2-aminophenyl disulfide, copper cyanide, and an electrophile to access N-substituted 2-amino benzothiazoles. Preliminary results in the use of the second method to access N-substituted 2-imino benzothiazoles are also reported.
- Castanheiro, Thomas,Suffert, Jean,Donnard, Morgan,Gulea, Mihaela
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p. 162 - 165
(2017/01/22)
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- Aerobic Copper-Mediated Domino Three-Component Approach to 2-Aminobenzothiazole Derivatives
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An unprecedented three-component reaction involving a 2,2′-diaminodiaryl disulfide, copper cyanide, and an electrophile is described. This transformation is based on an oxidative copper-mediated S-cyanation as a key step and involves a cyanation/cyclization/acylation domino sequence enabling a rapid and efficient synthesis of diversely substituted 2-aminobenzothiazole derivatives. Notably, this reaction proceeds via an original mechanism involving an intermolecular migration of the acyl group.
- Castanheiro, Thomas,Suffert, Jean,Gulea, Mihaela,Donnard, Morgan
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supporting information
p. 2588 - 2591
(2016/06/15)
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- Novel solid-phase parallel synthesis of N-substituted-2-aminobenzo [d]thiazole derivatives via cyclization reactions of 2-iodophenyl thiourea intermediate resin
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A novel solid-phase methodology has been developed for the synthesis of N-alkyl, N-acyl, and N-sulfonyl-2-aminobenzo[d]thiazole derivatives. The key step in this procedure involves the preparation of polymer-bound 2-aminobenzo[d]thiazole resins 5 by cyclization reaction of 2-iodophenyl thiourea resin 3. The resin-bound 2-iodophenyl thiourea 3 is produced by addition of 2-iodophenyl isothiocyanate 2 to the amine-terminated linker amide resin 1. These core skeleton 2-aminobenzo[d]thiazole resins 5 undergo functionalization reactions with various electrophiles, such as alkyl halides, acid chlorides, and sulfonyl chlorides to generate N-alkyl, N-acyl, and N-sulfonyl-2-aminobenzo[d]thiazole resins 6, 7, and 8, respectively. Finally, N-alkyl, N-acyl, and N-sulfonyl-2-aminobenzo[d]thiazole derivatives 9, 10, and 11 are then generated in good yields and purities by cleavage of the respective resins 6, 7, and 8 using trifluoroacetic acid (TFA) in dichloromethane (DCM).
- Kim, Seul-Gi,Jung, Se-Lin,Lee, Gee-Hyung,Gong, Young-Dae
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