- Tunable Electrosynthesis of Anthranilic Acid Derivatives via a C-C Bond Cleavage of Isatins
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A facile and direct electrocatalytic C-C bond cleavage/functionalization reaction of isatins was developed. With isatins as the amino-attached C1 sources, a variety of aminobenzoates, and aminobenzamides were synthesized in moderate to good yields under mild conditions.
- Qian, Peng,Liu, Jiaojiao,Zhang, Yan,Wang, Zhiyong
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p. 16008 - 16015
(2021/07/31)
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- Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu7Positive Allosteric Modulator Tool Compound
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Herein, we report the discovery of the first selective and CNS penetrant mGlu7 PAM (VU6027459) derived from a "molecular switch"within a selective mGlu7 NAM chemotype. VU6027459 displayed CNS penetration in both mice (Kp = 2.74) and rats (Kp= 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.
- Reed, Carson W.,Kalbfleisch, Jacob J.,Wong, Madison J.,Washecheck, Jordan P.,Hunter, Ashton,Rodriguez, Alice L.,Blobaum, Anna L.,Conn, P. Jeffrey,Niswender, Colleen M.,Lindsley, Craig W.
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supporting information
p. 1773 - 1779
(2020/10/19)
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- Oxidative ring-opening of isatins for the synthesis of 2-aminobenzamides and 2-aminobenzoates
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An efficient and practical isatin-based oxidative domino protocol has been developed for the facile synthesis of 2-aminobenzamides and 2-aminobenzoates. The robust nature of this reaction system is reflected by accessible starting materials, room temperature and high-yield gram-scale synthesis.
- Wang, Yu-Wei,Zheng, Lei,Jia, Feng-Cheng,Chen, Yun-Feng,Wu, An-Xin
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p. 1497 - 1503
(2019/02/13)
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- Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators
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Neurotensin receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based lead to give 18 (SBI-553), a potent and brain penetrant NTR1 allosteric modulator.
- Pinkerton, Anthony B.,Peddibhotla, Satyamaheshwar,Yamamoto, Fusayo,Slosky, Lauren M.,Bai, Yushi,Maloney, Patrick,Hershberger, Paul,Hedrick, Michael P.,Falter, Bekhi,Ardecky, Robert J.,Smith, Layton H.,Chung, Thomas D. Y.,Jackson, Michael R.,Caron, Marc G.,Barak, Lawrence S.
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supporting information
p. 8357 - 8363
(2019/09/10)
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- Weak, bidentate chelating group assisted cross-coupling of C(sp3)-H bonds in aliphatic acid derivatives with aryltrifluoroborates
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A protocol of Pd(ii)-catalyzed, weak bidentate directing group assisted β-C(sp3)-H activation/cross-coupling with organoboron reagents has been achieved, affording arylation of aliphatic acid derivatives that contain α-hydrogen atoms in moderate to good yields. The potential of this method for an asymmetric β-C(sp3)-H arylation via desymmetrization was also presented.
- Cai, Zhihua,Li, Shangda,Gao, Yuzhen,Fu, Lei,Li, Gang
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supporting information
p. 12766 - 12769
(2018/11/23)
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- Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study
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GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a screening hit. The oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. A mean EC50 = 0.43 nM was found toward a panel of 75 RSV A and B clinical isolates and dose-dependent antiviral efficacy in the cotton rat model of RSV infection. Oral bioavailability in preclinical species ranged from 46 to 100%, with evidence of efficient penetration into lung tissue. In healthy human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a mean 4.2 log10 reduction in peak viral load and a significant reduction in disease severity compared to placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV infection in infants and adults is reported.
- Mackman, Richard L.,Sangi, Michael,Sperandio, David,Parrish, Jay P.,Eisenberg, Eugene,Perron, Michel,Hui, Hon,Zhang, Lijun,Siegel, Dustin,Yang, Hai,Saunders, Oliver,Boojamra, Constantine,Lee, Gary,Samuel, Dharmaraj,Babaoglu, Kerim,Carey, Anne,Gilbert, Brian E.,Piedra, Pedro A.,Strickley, Robert,Iwata, Quynh,Hayes, Jaclyn,Stray, Kirsten,Kinkade, April,Theodore, Dorothy,Jordan, Robert,Desai, Manoj,Cihlar, Tomas
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supporting information
p. 1630 - 1643
(2015/04/27)
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- AGONISTS OF THE APELIN RECEPTOR AND METHODS OF USE THEREOF
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Provided herein are small molecule agonists of the apelin receptor for the treatment of disease. The compounds disclosed herein are useful for the treatment of a range of cardiovascular, renal and metabolic conditions.
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Paragraph 0333; 0334; 0335
(2015/12/31)
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- COMPOUNDS AND METHODS FOR ANTIVIRAL TREATMENT
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Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections
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Paragraph 0808-0811
(2013/10/22)
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- Hofmann-type rearrangement of imides by in situ generation of imide-hypervalent iodines(III) from iodoarenes
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The Hofmann-type rearrangement of aromatic and aliphatic imides using a hypervalent iodine(III) reagent generated in situ from PhI, m-CPBA, and TsOH·H2O proceeded in the presence of a base in alcohol to provide anthranilic acid derivatives and amino acid derivatives in high yields, respectively. This reaction proceeds through a tandem reaction via alcoholysis followed by a Hofmann rearrangement promoted by the formation of an imide-λ3-iodane intermediate.
- Moriyama, Katsuhiko,Ishida, Kazuma,Togo, Hideo
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supporting information; experimental part
p. 946 - 949
(2012/05/05)
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- PYRAZOLO [1, 5 -A] PYRIMIDINES AS ANTIVIRAL AGENTS
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The invention provides compounds of Formula I or Formula II: (I), (II) or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.
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Page/Page column 158
(2012/01/14)
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- QUINOLIN-4-ONE AND 4-OXODIHYDROCINNOLINE DERIVATIVES AS INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
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The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts or tautomers thereof which are inhibitors of poly(ADP- ribose)polymerase (PARP) and thus useful for the treatment of cancer, inflammatory diseases, reperfusio
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Page/Page column 55
(2009/04/25)
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