- Quinolone-based compounds, formulations, and uses thereof
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Provided herein are quinolone-based compounds that can be used for treatment and/or prevention of malaria and formulations thereof. Also provided herein are methods of treating and/or preventing malaria in a subject by administering a quinolone-based compound or formulation thereof provided herein.
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Page/Page column 117
(2018/07/02)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 0539; 0540; 0541
(2016/09/26)
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- ICI 56,780 optimization: Structure-activity relationship studies of 7-(2-phenoxyethoxy)-4(1H)-quinolones with antimalarial activity
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Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.
- Maignan, Jordany R.,Lichorowic, Cynthia L.,Giarrusso, James,Blake, Lynn D.,Casandra, Debora,Mutka, Tina S.,LaCrue, Alexis N.,Burrows, Jeremy N.,Willis, Paul A.,Kyle, Dennis E.,Manetsch, Roman
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p. 6943 - 6960
(2016/08/05)
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- Synthesis and antiparasitic activity of new bis-arylimidamides: DB766 analogs modified in the terminal groups
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Fifteen novel bis-arylimidamide derivatives with various 6-membered (7a-c) and 5-membered (7d-o) heterocyclic rings replacing the terminal pyridyl rings of the lead compound DB766{(2,5-bis[2-i-propoxy-4-(2-pyridylimino) aminophenylfuran]}, were prepared a
- Liu, Zong-Ying,Wenzler, Tanja,Brun, Reto,Zhu, Xiaohua,Boykin, David W.
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p. 167 - 173
(2014/07/08)
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- 4(1H)-Quinolones Having Antimalarial Activity With Reduced Chemical Resistance
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Provided are 4(1H)-quinolone derivatives effective in inhibiting or eliminating the viability of at least one of the stages in the life-cycle of the malarial parasite, and to show a reduced propensity to induce resistance to the compound by the target parasite. In particular, the compounds can be derivatives of phenoxyethoxy-quinolones, and including, but not only, 7-(2-phenoxyethoxy)quinolin derivatives. These compounds may be administered by themselves, with at least one other derivative compound, or with other antimalarial compounds, to an animal or human subject. The therapeutic compositions can be and formulated to reduce the extent of a Plasmodium infection in the recipient subject, or to reduce the likelihood of the onset or establishment of a Plasmodium infection if administered prior to the parasite contacting the subject. The therapeutic compositions can be formulated to provide an effective single dose amount of an antimalarial compound or multiple doses for administering over a period of time.
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Paragraph 0226; 0227; 0228
(2013/05/22)
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- SULFONAMIDE COMPOUNDS USEFUL AS CYP17 INHIBITORS
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Disclosed are sulfonamide compounds of Formula (I): or stereoisomers, N-oxides, prodrugs, or pharmaceutically acceptable salts thereof, wherein ring A, R1, R2, R3, R4 and R5 are defined herein. Also disclosed are methods of using such compounds in the treatment of conditions related to CYP17 enzyme, such as cancer, and pharmaceutical compositions comprising such compounds.
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Page/Page column 79; 80
(2012/02/13)
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- Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-Phenoxyethoxy)-4(1H)-quinolones
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ICI 56,780 (5) displayed causal prophylactic and blood schizonticidal activity (ED50 = 0.05 mg/kg) in rodent malaria models but produced rapid acquisition of parasitological resistance in P. berghei infected mice. Herein we describe the synthesis of analogues of 5 with EC50 as low as 0.15 nM against multidrug resistant P. falciparum. Optimal activity with low cross-resistance indexes (RI) to atovaquone was achieved by introducing ortho-substituted aryl moieties at the 3-position of the 7-(2-phenoxyethoxy)- 4(1H)-quinolone core. (Figure presented
- Cross, R. Matthew,Namelikonda, Niranjan K.,Mutka, Tina S.,Luong, Lisa,Kyle, Dennis E.,Manetsch, Roman
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supporting information; experimental part
p. 8321 - 8327
(2012/02/04)
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- TRPV4 ANTAGONISTS
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The present invention relates to quinoline analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.
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Page/Page column 47
(2011/10/13)
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- MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
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The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating diseases using such CFTR modulators.
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Page/Page column 69; 70
(2010/07/08)
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- CHEMICAL COMPOUNDS
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The invention relates to chemical compounds of formula (I): or pharmaceutically acceptable salts thereof which possess CSF-IR kinase inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.
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Page/Page column 63; 64
(2010/01/29)
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- 3 - CINNOLINECARBOXAMIDE DERIVATIVES AND THEIR USE FOR TREATING CANCER
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The invention relates to chemical compounds of formula (I): Formula (I), or pharmaceutically acceptable salts thereof which possess CSF 1R kinase inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti cancer effect in a warm blooded animal such as man.
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Page/Page column 61
(2008/12/07)
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- Regioselective monobromination of substituted phenols in the presence of β-cyclodextrin
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Cyclodextrin acts as a restricting nanovessel to enhance regioselectivity in bromination of substituted phenols such as 3-nitrophenol, 2-chlorophenol, 3-chlorophenol, and 4-chlorophenol. In contrast to solution bromination, cyclodextrin facilitates regioselective monobromination and formation of polybrominated products are substantially reduced. Selectivities in brominations are also observed in water and in the solid state. The observed results are rationalized on the basis of specific modes of inclusion of substituted phenols inside the cyclodextrin cavity and find strong support from energy minimization studies and 1H-1H NOESY.
- Suresh, Palaniswamy,Annalakshmi, Subramanian,Pitchumani, Kasi
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p. 4959 - 4967
(2008/02/02)
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- Arylsulfonamide ethers, and methods of use thereof
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Novel arylsulfonamide ether compounds and pharmaceutical compositions thereof are described. The use of the novel arylsulfonamide ether compounds and pharmaceutical compositions thereof as inhibitors of interleukin-1β converting enzyme and other cysteine proteases in the ICE family is also decribed. In addition, methods of treating stroke, inflammatory diseases, septic shock, repurfusion injury, Alzheimer's disease, and shigellosis using a compound of the invention or a pharmaceutical composition thereof are described.
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- Further Evidence for the Triplet Mechanism in the Photosubstitution of Nitroaryl Ethers in Alkaline Medium.
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Mechanistic studies show that nitroaryl ethers (3-nitroanisole, 3-nitrophenetole, n-butyl 3-nitrophenyl ether, 2-chloro-5-nitroanisole, 2-bromo-5-nitroanisole and 3,5-dinitroanisole) undergo nucleophilic aromatic photosubstitution with hydroxide ions through an SN23Ar* mechanism.An investigation of the quenching of excited states of nitroaryl ethers by bromide and thiosulfate ions in aqueous solutions is reported and lends support to the proposed SN23Ar* mechanism.Key Words: Photosubstitution; Nitroaryl Ethers; Triplet Lifetime; Quencher.
- Bonilha, Joao Baptista Sargi,Tedesco, Antonio Claudio,Nogueira, Lazaro Cicero,Ribeiro, Maria Teresa,Diamantino, Silva,Carreiro, Julio Cesar
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p. 3053 - 3064
(2007/10/02)
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