- Design, synthesis and biological activity of multifunctional α,β-unsaturated carbonyl scaffolds for Alzheimer's disease
-
A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations include
- Bag, Seema,Ghosh, Sanjukta,Tulsan, Rekha,Sood, Abha,Zhou, Weihong,Schifone, Christine,Foster, Michelle,Levine III, Harry,T?r?k, Béla,T?r?k, Marianna
-
-
Read Online
- PYRUVATE KINASE ACTIVATORS FOR USE IN TREATING BLOOD DISORDERS
-
Described herein are compounds that activate pyruvate kinase R, pharmaceutical compositions and methods of use thereof. These compounds are represented by Formula (I): Formula (I) wherein R', R2, L', and L2 are as defined herein.
- -
-
Page/Page column 4
(2019/03/05)
-
- CHEMICAL COMPOUNDS
-
The present disclosure relates to compounds of Formula (I): and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein inhibit the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as inter alia autoinflammatory and autoimmune diseases and cancers.
- -
-
Page/Page column 51; 52
(2018/10/19)
-
- INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
-
The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
- -
-
Paragraph 240; 241; 242
(2016/10/11)
-
- Discovery of a Quinoline-4-carboxamide Derivative with a Novel Mechanism of Action, Multistage Antimalarial Activity, and Potent in Vivo Efficacy
-
The antiplasmodial activity, DMPK properties, and efficacy of a series of quinoline-4-carboxamides are described. This series was identified from a phenotypic screen against the blood stage of Plasmodium falciparum (3D7) and displayed moderate potency but with suboptimal physicochemical properties and poor microsomal stability. The screening hit (1, EC50 = 120 nM) was optimized to lead molecules with low nanomolar in vitro potency. Improvement of the pharmacokinetic profile led to several compounds showing excellent oral efficacy in the P. berghei malaria mouse model with ED90 values below 1 mg/kg when dosed orally for 4 days. The favorable potency, selectivity, DMPK properties, and efficacy coupled with a novel mechanism of action, inhibition of translation elongation factor 2 (PfEF2), led to progression of 2 (DDD107498) to preclinical development.
- Baragana, Beatriz,Norcross, Neil R.,Wilson, Caroline,Porzelle, Achim,Hallyburton, Irene,Grimaldi, Raffaella,Osuna-Cabello, Maria,Norval, Suzanne,Riley, Jennifer,Stojanovski, Laste,Simeons, Frederick R. C.,Wyatt, Paul G.,Delves, Michael J.,Meister, Stephan,Duffy, Sandra,Avery, Vicky M.,Winzeler, Elizabeth A.,Sinden, Robert E.,Wittlin, Sergio,Frearson, Julie A.,Gray, David W.,Fairlamb, Alan H.,Waterson, David,Campbell, Simon F.,Willis, Paul,Read, Kevin D.,Gilbert, Ian H.
-
supporting information
p. 9672 - 9685
(2016/11/19)
-
- SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
-
Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.
- -
-
Paragraph 0333; 0334
(2014/09/30)
-
- COMPOUNDS USEFUL AS RETINOID-RELATED ORPHAN RECEPTOR GAMMA MODULATORS
-
Disclosed are retinoid-related orphan receptor gamma (RORγ) modulators of Formula (I) and their use in the treatment of diseases mediated by RORγ, wherein the radicals have the meanings as defined in the invention.
- -
-
Page/Page column 38
(2012/08/08)
-
- Competition between azido cleavage and triplet nitrene formation in azidomethylacetophenones
-
Photolysis of p- and m-azidomethylacetophenone (1a, 1b) in argon-saturated solutions yields predominantly imine 2a, 2b, whereas irradiation of 1a, 1b in oxygen-saturated solutions results in heterocycles 3a, 3b, aldehydes 4a, 4b and nitriles 5a, 5b. Density functional theory calculations place the energy of the first and second excited state of the triplet ketones (T1K and T 2K) in 1a, 1b in close proximity to each other. The triplet transition state for cleaving the CN bond in 1a, 1b to form azido and benzyl radicals 1aB, 1bB is located only 3 kcal mol-1 (1 kcal = 4.184 kJ) above T1K, indicating that azido cleavage is feasible. The calculations place the energy of the triplet azido group (TA) in 1a, 1b ~25 kcal mol-1 below T1K; thus, this process is also easily accessible via energy transfer. Further, the transition state barrier for TA to expel N2 and form triplet nitrenes is less than 1 kcal mol-1 above TA in 1a, 1b. Laser flash photolysis of 1a, 1b reveals the formation of the triplet excited ketones of 1a, 1b, which decay to form benzyl radicals 1aB, 1bB and triplet alkylnitrenes. The triplet ketones and the benzyl radicals are quenched with molecular oxygen at rates close to diffusion, whereas the triplet nitrenes react more slowly with oxygen (~5 × 105 M-1s-1). We conclude that the triplet alkylnitrenes intercept the benzyl radicals to form 2 in argon-saturated solution, whereas the benzyl radicals are trapped to form 4 in oxygen-saturated solution; thus, the triplet nitrenes react with oxygen to form 3. CSIRO 2010.
- Ranaweera, Ranaweera A. A. Upul,Zhao, Yu,Muthukrishnan, Sivaramakrishnan,Keller, Christopher,Gudmundsdottir, Anna D.
-
experimental part
p. 1645 - 1655
(2011/09/14)
-
- LANTHANIDE(III) CHELATES COMPRISING BETA-DIKETONES AND CONJUGATES DERIVED THEREOF
-
This invention relates to luminescent lanthanide(III) chelates based on β-diketones comprising an azacycloalkane backbone and biomolecule conjugates and solid supports comprising these chelates. In contrast to lanthanide chelates based on monomeric β-diketones as well as lanthanide(III) chelates based on acyclic azaalkanes including several β-diketone subunits, the molecules of the present technology are luminescent even in the absence of additional chelators such as phosphine oxides.
- -
-
Page/Page column 10; 17
(2009/10/22)
-
- Substituted isoxazolines, pharmaceutical compositions containing the same, methods of preparing the same, and uses of the same
-
The invention relates to substituted isoxazolines according to the general formula (I) : in which A, R1, R2, R3, R4, Z, X, m, n, and p, are given in the claims, and salts thereof, to pharmaceutical compositions comprising said substituted isoxazolines, to methods of preparing said substituted isoxazolines as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases known to be at least in part mediated by HDAC activity or whose symptoms are known to be alleviated by HDAC inhibitors.
- -
-
Page/Page column 20
(2008/06/13)
-
- 2-AMINOPHENYL-4-PHENYLPYRIMIDINES AS KINASE INHIBITORS
-
The present invention relates to compounds of Formula: (I), or pharmaceutically acceptable salt thereof, wherein the variables are defined in the description. The compounds act as kinase inhibitors.
- -
-
Page/Page column 47-48
(2010/02/10)
-
- Amine derivatives
-
The present invention relates to amine derivatives represented by formula (1) or salts thereof. R3represents C1-C3 alkyl, hydroxylated C1-C5 alkyl, C1-C5 acyl; C2-C5 alkenyl, or a halogen atom; and k, l, and m are each an integer of 1 to 4.) Exhibiting excellent antifungal effect, these compounds are highly useful as antifungal agents, antifungal compositions, drugs, etc.
- -
-
-
- Azido-containing aryl β-diketo acid HIV-1 integrase inhibitors
-
Aryl β-diketo acids (ADK) comprise a general class of potent HIV-1 integrase (IN) inhibitors, which can exhibit selective inhibition of strand transfer reactions in extracellular recombinant IN assays and provide potent antiviral effects in HIV-infected cells. Recent studies have shown that polycyclic aryl or aryl rings bearing aryl-containing substituents are components of potent members of this class. Reported herein is the first use of azido functionality as an aryl replacement in β-diketo acid IN inhibitors. The ability of azido-containing inhibitors to exhibit potent inhibition of IN and antiviral protection in HIV-infected cells, renders the azide group of potential value in the further development of ADK-based IN inhibitors.
- Zhang, Xuechun,Pais, Godwin C.G.,Svarovskaia, Evguenia S.,Marchand, Christophe,Johnson, Allison A.,Karki, Rajeshri G.,Nicklaus, Marc C.,Pathak, Vinay K.,Pommier, Yves,Burke Jr., Terrence R.
-
p. 1215 - 1219
(2007/10/03)
-
- Synthesis of phenylglycine derivatives as potent and selective antagonists of group III metabotropic glutamate receptors
-
The syntheses of a range of ring and α-substituted 4-phosphonophenylglycines are described. A brief discussion of the antagonist activities of compounds 4-10 on group I, II and III metabotropic glutamate (mGlu) receptors expressed in the neonatal rat spin
- Conway, Stuart J,Miller, Jacqueline C,Howson, Patrick A,Clark, Barry P,Jane, David E
-
p. 777 - 780
(2007/10/03)
-