- SUBSTITUTED CYCLOPROPYL-2,2'-BIPYRIMIDINYL COMPOUNDS, ANALOGUES THEREOF, AND METHODS USING SAME
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The present disclosure includes novel substituted cyclopropyl-2,2'-bipyrimidinyl compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infection and/or hepatitis D virus (HDV) infection in a patient.
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Page/Page column 212; 213
(2021/02/12)
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- BENZOXABOROLE COMPOUNDS AND FORMULATIONS THEREOF
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A benzoxaborole formulation composition including a benzoxaborole, a non-ionic surfactant, or a non-ionic and ionic surfactant mixture, and a carrier is described herein. At least one of the non-ionic surfactant, the non-ionic and ionic surfactant mixture
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Paragraph 00281
(2019/06/17)
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- 5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma
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Through a phenotypic high-throughput screen using a serum response element luciferase promoter, we identified a novel 5-aryl-1,3,4-oxadiazol-2-ylthiopropionic acid lead inhibitor of Rho/myocardin-related transcription factor (MRTF)/serum response factor (SRF)-mediated gene transcription with good potency (IC50 = 180 nM). We were able to rapidly improve the cellular potency by 5 orders of magnitude guided by sharply defined and synergistic SAR. The remarkable potency and depth of the SAR, as well as the relatively low molecular weight of the series, suggests, but does not prove, that binding to the unknown molecular target may be occurring through a covalent mechanism. The series nevertheless has no observable cytotoxicity up to 100 μM. Ensuing pharmacokinetic optimization resulted in the development of two potent and orally bioavailable anti-fibrotic agents that were capable of dose-dependently reducing connective tissue growth factor gene expression in vitro as well as significantly reducing the development of bleomycin-induced dermal fibrosis in mice in vivo.
- Kahl, Dylan J.,Hutchings, Kim M.,Lisabeth, Erika Mathes,Haak, Andrew J.,Leipprandt, Jeffrey R.,Dexheimer, Thomas,Khanna, Dinesh,Tsou, Pei-Suen,Campbell, Phillip L.,Fox, David A.,Wen, Bo,Sun, Duxin,Bailie, Marc,Neubig, Richard R.,Larsen, Scott D.
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p. 4350 - 4369
(2019/05/08)
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- Design, Synthesis, and Evaluation of Novel Auxin Mimic Herbicides
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Due to the key roles of auxins as master regulators of plant growth, there is considerable interest in the development of compounds with auxin-like properties for growth management and weed control applications. Herein, we describe the design and multiste
- Do-Thanh, Chi-Linh,Vargas, Jose J.,Thomas, Joseph W.,Armel, Gregory R.,Best, Michael D.
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p. 3533 - 3537
(2016/06/01)
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- SUBSTITUTED ISOXAZOLINE DERIVATIVES
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This invention recites substituted isoxazoline derivatives of Formula (1) or a veterinarily acceptable salt thereof, with parasiticidal activity, compositions thereof, and their use as a parasiticide in animals or birds where R1a, R1b/sup
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Page/Page column 19
(2011/10/19)
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- Discovery, synthesis and SAR of azinyl- and azolylbenzamides antagonists of the P2X7 receptor
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The discovery, of a series of 2-Cl-5-heteroaryl-benzamide antagonists of the P2X7 receptor via parallel medicinal chemistry is described. Initial analogs suffered from poor metabolic stability and low Vdss. Multi parametric optimizat
- Subramanyam, Chakrapani,Duplantier, Allen J.,Dombroski, Mark A.,Chang, Shang-Poa,Gabel, Christopher A.,Whitney-Pickett, Carrie,Perregaux, David G.,Labasi, Jeff M.,Yoon, Kwansik,Shepard, Richard M.,Fisher, Michael
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scheme or table
p. 5475 - 5479
(2011/10/12)
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- Synthesis and in vitro antiprotozoal activities of dicationic 3,5-diphenylisoxazoles
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3,5-Bis(4-amidinophenyl)isoxazole (3) - an analogue of 2,5-bis(4- amidinophenyl)furan (furamidine) in which the central furan ring is replaced by isoxazole - and 42 novel analogues were prepared by two general synthetic pathways. The 43 isoxazole derivati
- Patrick, Donald A.,Bakunov, Stanislav A.,Bakunova, Svetlana M.,Kumar, E.V.K. Suresh,Lombardy, Richard J.,Jones, Susan Kilgore,Bridges, Arlene S.,Zhirnov, Oksana,Hall, James Edwin,Wenzler, Tanja,Brun, Reto,Tidwell, Richard R.
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p. 2468 - 2485
(2008/02/03)
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- Discovery of 5-HT6 receptor ligands based on virtual HTS
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Based on a pharmacophore alignment on a 5-HT6 ligand applying 4SCan technology, a new lead series was identified and further structurally investigated. Kis down to 8 nM were achieved.
- Tasler, Stefan,Kraus, Jürgen,Wuzik, Andreas,Müller, Oliver,Aschenbrenner, Andrea,Cubero, Elena,Pascual, Rosalia,Quintana-Ruiz, Jordi-Ramon,Dordal, Alberto,Mercè, Ramon,Codony, Xavier
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p. 6224 - 6229
(2008/03/18)
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- Synthesis and antiprotozoal activity of dicationic 3,5-diphenylisoxazoles
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Novel dicationic 3,5-diphenylisoxazole compounds are described. Synthetic routes to these novel compounds are provided. Several of the compounds displayed in vitro activity versus Trypanosoma brucei brucei and Plasmodium falciparum comparable to that of furamidine. A majority of the novel compounds also were less toxic to VERO cells than furamidine.
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Page/Page column 24-28; 41
(2010/11/24)
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- Aryl triazines as LPAAT-SS inhibitors and uses thereof
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The invention relates to aryl triazines and uses thereof, including to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity and/or proliferation of cells such as tumor cells.
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