146611-58-7Relevant articles and documents
Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory
Klucznik, Tomasz,Mikulak-Klucznik, Barbara,McCormack, Michael P.,Lima, Heather,Szymku?, Sara,Bhowmick, Manishabrata,Molga, Karol,Zhou, Yubai,Rickershauser, Lindsey,Gajewska, Ewa P.,Toutchkine, Alexei,Dittwald, Piotr,Startek, Micha? P.,Kirkovits, Gregory J.,Roszak, Rafa?,Adamski, Ariel,Sieredzińska, Bianka,Mrksich, Milan,Trice, Sarah L.J.,Grzybowski, Bartosz A.
, p. 522 - 532 (2018)
The Chematica program was used to autonomously design synthetic pathways to eight structurally diverse targets, including seven commercially valuable bioactive substances and one natural product. All of these computer-planned routes were successfully executed in the laboratory and offer significant yield improvements and cost savings over previous approaches, provide alternatives to patented routes, or produce targets that were not synthesized previously. Although computers have demonstrated the ability to challenge humans in various games of strategy, their use in the automated planning of organic syntheses remains unprecedented. As a result of the impact that such a tool could have on the synthetic community, the past half century has seen numerous attempts to create in silico chemical intelligence. However, there has not been a successful demonstration of a synthetic route designed by machine and then executed in the laboratory. Here, we describe an experiment where the software program Chematica designed syntheses leading to eight commercially valuable and/or medicinally relevant targets; in each case tested, Chematica significantly improved on previous approaches or identified efficient routes to targets for which previous synthetic attempts had failed. These results indicate that now and in the future, chemists can finally benefit from having an “in silico colleague” that constantly learns, never forgets, and will never retire. Multistep synthetic routes to eight structurally diverse and medicinally relevant targets were planned autonomously by the Chematica computer program, which combines expert chemical knowledge with network-search and artificial-intelligence algorithms. All of the proposed syntheses were successfully executed in the laboratory and offer substantial yield improvements and cost savings over previous approaches or provide the first documented route to a given target. These results provide the long-awaited validation of a computer program in practically relevant synthetic design.
Amino acid derivatives having antiviral activity
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, (2008/06/13)
Compounds of the formula: STR1 wherein R1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, heterocyclylcarbonyl or a group of the formula: STR2 R2 is alkyl, cycloalkylalkyl or aralkyl; R3 is hydrogen and R4 is hydroxy or R3 and R4 together are oxo; R5 is alkoxycarbonyl or alkylcarbamoyl; R6 and R7 together are trimethylene or tetramethylene optionally substituted by alkyl or on adjacent carbon atoms by tetramethylene; R8 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aroyl, aralkanoyl or heterocyclylcarbonyl; and R9 is alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, cyanoalkyl, carbamoyl-alkyl, alkylthioalkyl, alkoxyalkyl or alkoxycarbonylalkyl: and pharmaceutically acceptable acid addition salts of those compounds of formula I which are basic, inhibit aspartyl proteases of viral origin and can be used in the form of medicaments for the prophylaxis or treatment of viral infections. They can be manufactured according to generally known methods.
