149108-74-7Relevant academic research and scientific papers
Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration
Tresadern, Gary,Velter, Ingrid,Trabanco, Andrés A.,Van Den Keybus, Frans,MacDonald, Gregor J.,Somers, Marijke V. F.,Vanhoof, Greet,Leonard, Philip M.,Lamers, Marieke B. A. C.,Van Roosbroeck, Yves E. M.,Buijnsters, Peter J. J. A.
, p. 12887 - 12910 (2020/11/13)
We describe the hit-To-lead exploration of a [1,2,4]triazolo[1,5-A]pyrimidine phosphodiesterase 2A (PDE2A) inhibitor arising from high-Throughput screening. X-ray crystallography enabled structure-guided design, leading to the identification of preferred substructural components. Further rounds of optimization used relative binding free-energy calculations to prioritize different substituents from the large accessible chemical space. The free-energy perturbation (FEP) calculations were performed for 265 putative PDE2A inhibitors, and 100 compounds were synthesized representing a relatively large prospective application providing unexpectedly active molecules with IC50′s from 2340 to 0.89 nM. Lead compound 46 originating from the FEP calculations showed PDE2A inhibition IC50 of 1.3 ± 0.39 nM, a 100-fold selectivity versus other PDE enzymes, clean cytochrome P450 profile, in vivo target occupancy, and promise for further lead optimization.
Cyclic Alkenylsulfonyl Fluorides: Palladium-Catalyzed Synthesis and Functionalization of Compact Multifunctional Reagents
Lou, Terry Shing-Bong,Bagley, Scott W.,Willis, Michael C.
supporting information, p. 18859 - 18863 (2019/11/19)
A series of low-molecular-weight, compact, and multifunctional cyclic alkenylsulfonyl fluorides were efficiently prepared from the corresponding alkenyl triflates. Palladium-catalyzed sulfur dioxide insertion using the surrogate reagent DABSO effects sulfinate formation, before trapping with an F electrophile delivers the sulfonyl fluorides. A broad range of functional groups are tolerated, and a correspondingly large collection of derivatization reactions are possible on the products, including substitution at sulfur, conjugate addition, and N-functionalization. Together, these attributes suggest that this method could find new applications in chemical biology.
TRISUBSTITUTED PYRIMIDINE COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER, RETINAL DISORDERS, AND CARDIOMYOPATHIES
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Page/Page column 35; 36, (2018/11/26)
The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular in the treatment of
ANTI-AMYLOID COMPOUNDS CONTAINING BENZOFURAZAN
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, (2017/07/14)
In general, among other things, compounds of Formula I are provided: in which R11 is e.g., 4-(pyrrolidin-1-yl)piperidin-1-yl, N-methyl-3-(pyrrolidin-1-yl)propan-1-amino, N1,N1,N3-trimethylpropane-1,3-diamino, N,N-dimethylpiperidin-4-amino, 3-(pyrrolidin-1-ylmethyl)azetidin-1-yl, 3-(pyrrolidin-1-ylmethanon)azetidin-1-yl, or 3-(morpholin-1-ylmethyl)azetidin-1-yl; R13 is, e.g., phenyl optionally substituted with one or more substituents; and R12 and R14 are each independently hydrogen or alkyl. Methods of treatment are also provided.
Aminoheteroaryl benzamides as kinase inhibitors
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Page/Page column 385; 388, (2016/02/15)
The present invention provides a compound of Formula (I) or a salt thereof; and therapeutic uses of these compounds. The present invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds with a therapeutic co-agent.
SUBSTITUTED NICOTINIMIDE INHIBITORS OF BTK AND THEIR PREPARATION AND USE IN THE TREATMENT OF CANCER, INFLAMMATION AND AUTOIMMUNE DISEASE
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Page/Page column 44, (2015/04/15)
Compounds of Formula I, as shown below and defined herein: and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).
Development of a Suzuki cross-coupling reaction between 2-azidoarylboronic pinacolate esters and vinyl triflates to enable the synthesis of [2,3]-fused indole heterocycles
Jana, Navendu,Nguyen, Quyen,Driver, Tom G.
, p. 2781 - 2791 (2014/04/17)
The scope and limitations of a Suzuki reaction between 2-azidoarylboronic acid pinacolate esters and vinyl triflates are reported. This cross-coupling reaction enables the regioselective synthesis of indoles after a subsequent RhII2-catalyzed sp2-C-H bond amination reaction.
Pyrimidin-4-one derivatives and their use in the treatment, amelioration or prevention of a viral disease
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Paragraph 0183, (2013/05/08)
The present invention relates to a compound having the general formula II, optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
Heteroaryl hydroxamic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease
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Paragraph 0169; 0170, (2013/05/08)
The present invention relates to a compound having the general formula I, optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameliorating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
Direct imine acylation: Synthesis of the proposed structures of 'upenamide
Unsworth, William P.,Gallagher, Katherine A.,Jean, Micka?l,Schmidt, Jan Peter,Diorazio, Louis J.,Taylor, Richard J. K.
supporting information, p. 262 - 265 (2013/03/14)
The synthesis of the two proposed structures of macrocyclic marine natural product 'upenamide is reported. The key step utilizes direct imine acylation (DIA) with a protected β-hydroxy acid to construct the key tricyclic ABC ring system. The macrocyclizat
