Author
Subas M. Sakya
Other affiliations: Purdue University
Bio: Subas M. Sakya is an academic researcher from Pfizer. The author has contributed to research in topics: Nucleophilic substitution & Tetrazine. The author has an hindex of 25, co-authored 77 publications receiving 1614 citations. Previous affiliations of Subas M. Sakya include Purdue University.
Papers published on a yearly basis
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TL;DR: Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.
Abstract: 3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a Biacore assay. Cocrystallization of 2 with the human DAAO enzyme defined the binding site and guided the design of new analogues. The SAR, pharmacokinetics, brain exposure, and effects on cerebellum D-serine are described. Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.
108 citations
99 citations
TL;DR: This review covers the syntheses of 21 NCEs marketed in 2009 and provides insights into molecular recognition and also serves as leads for designing future new drugs.
98 citations
81 citations
TL;DR: This review covers the syntheses of 23 NCEs marketed in 2003 and provides insights into molecular recognition, but also serves as drug-like leads for designing new future drugs.
Abstract: New drugs are introduced to the market every year and each individual drug represents a privileged structure for its biological target. In addition, these new chemical entities (NCEs) not only provide insights into molecular recognition, but also serve as drug-like leads for designing new future drugs. To these ends, this review covers the syntheses of 23 NCEs marketed in 2003.
70 citations
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TL;DR: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012, and the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide.
Abstract: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012. In the case of all approved therapeutic agents, the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide. As mentioned in the 2012 review, we have continued to utilize our secondary subdivision of a “natural product mimic”, or “NM”, to join the original primary divisions and the designation “natural product botanical”, or “NB”, to cover those botanical “defined mixtures” now recognized as drug entities by the U.S. FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over t...
4,337 citations
TL;DR: A number of methods using various copper complexes and salts to carry out cross-coupling reactions leading to the formation of C heteroatom (C N, C O, C S, C P, C Se), C C, and C metal bonds have been proposed as discussed by the authors.
1,361 citations
839 citations
TL;DR: The history and development of coupling reactions between aryl halides and various classes of nucleophiles is discussed, focusing mostly on the different mechanisms proposed through the years.
Abstract: Cu-catalysed arylation reactions devoted to the formation of C–C and C–heteroatom bonds (Ullmann-type couplings) have acquired great importance in the last decade. This review discusses the history and development of coupling reactions between aryl halides and various classes of nucleophiles, focusing mostly on the different mechanisms proposed through the years. Selected mechanistic investigations are treated more in depth than others. For example, evidence in favour or against radical mechanisms is discussed. Cu(I) and Cu(III) complexes involved in the Ullmann reaction and N/O selectivity in aminoalcohol arylation are discussed. A separate section has been dedicated to the synthesis of heterocyclic rings through intramolecular couplings. Finally, recent developments in green chemistry for these reactions, such as reactions in aqueous media and heterogeneous catalysis, have also been reviewed.
799 citations
TL;DR: The many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules make it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials.
Abstract: Quaternary carbon stereocentres-carbon atoms to which four distinct carbon substituents are attached-are common features of molecules found in nature. However, before recent advances in chemical catalysis, there were few methods of constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules. This progress now makes it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials.
662 citations