- Ligand-Enabled β-Methylene C(sp3)?H Arylation of Masked Aliphatic Alcohols
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Despite recent advances, reactivity and site-selectivity remain significant obstacles for the practical application of C(sp3)?H bond functionalization methods. Here, we describe a system that combines a salicylic-aldehyde-derived L,X-type directing group with an electron-deficient 2-pyridone ligand to enable the β-methylene C(sp3)?H arylation of aliphatic alcohols, which has not been possible previously. Notably, this protocol is compatible with heterocycles embedded in both alcohol substrates and aryl coupling partners. A site- and stereo-specific annulation of dihydrocholesterol and the synthesis of a key intermediate of englitazone illustrate the practicality of this method.
- Liu, Luo-Yan,Melillo, Bruno,Schreiber, Stuart L.,Xia, Guoqin,Yu, Jin-Quan,Zhuang, Zhe
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supporting information
p. 7783 - 7787
(2020/03/23)
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- PROCESS FOR THE PREPARATION OF QUINOLONE BASED COMPOUNDS
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The present invention relates to an improved process for the preparation of quinolone based compounds of general formula (I) using intermediate compound of general formula (XII). Invention also provides an improved process for the preparation of compound of formula (I-a) using intermediate compound of formula (XII-a) and some novel impurities generated during process. Compounds prepared using this process can be used to treat anemia.
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Paragraph 0241-0243; 0266-0268; 0275-0276
(2019/12/06)
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- HETEROCYCLIC COMPOUNDS AS MEK INHIBITORS
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The invention provides novel substituted heterocyclic compounds represented by Formula I and Formula II, or a pharmaceutically acceptable salt, solvate, polymorph, ester, tauntomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of MEK and are useful in the treatment of inflammatory diseases, cancer and other hyperproliferative diseases. The invention further provides a method of treatment for inflammatory diseases, cancer and other hyperproliferative diseases in mammals, especially humans
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Page/Page column 21
(2012/09/25)
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- Design, Synthesis, and invitro Antibacterial Activity of Fluoroquinolone Derivatives Containing a Chiral 3-(Alkoxyimino)-2-(aminomethyl)azetidine Moiety
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A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1-azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their invitro antibacterial activity against representative strains. Our results reveal that 12 of the target compounds generally show better activity (MIC: -1) against the tested Gram-positive strains including MRSA and MRSE than levofloxacin (LVFX, MIC: 0.125-8μgmL-1). Their activity is similar to that of gemifloxacin (GMFX, MIC: -1). However, they are generally less active than the two reference drugs against Gram-negative strains. Moreover, against clinical strains of S.aureus including MRSA and S.epidermidis including MRSE, the MIC50 values (0.06-16μgmL-1) and MIC90 values (0.5-32μgmL-1) of compounds 16w, y, and z are 2-8- and 2-16-fold less than LVFX, respectively, and 16w (MIC90 range: 0.5-4μgmL-1) was also found to be more active than GMFX (MIC90 range: 1-8μgmL-1).
- Lv, Kai,Sun, Yexin,Sun, Lanyin,Wei, Zengquan,Guo, Huiyuan,Wu, Jinwei,Liu, Mingliang
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experimental part
p. 1230 - 1236
(2012/08/08)
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- NOVEL COMPOUNDS AS RESPIRATORY STIMULANTS FOR TREATMENT OF BREATHING CONTROL DISORDERS OR DISEASES
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The present invention includes compositions that are useful in the treatment of breathing control diseases or disorders in a subject in need thereof. The present invention also includes a method of treating a respiratory disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention, The present invention further includes a method of preventing destabilization or stabilizing breathing rhythm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical formulation of the invention.
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Page/Page column 101
(2012/06/16)
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- The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901
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A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzam ide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modification of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-b enzamide PD 0325901.
- Barrett, Stephen D.,Bridges, Alexander J.,Dudley, David T.,Saltiel, Alan R.,Fergus, James H.,Flamme, Cathlin M.,Delaney, Amy M.,Kaufman, Michael,LePage, Sophie,Leopold, Wilbur R.,Przybranowski, Sally A.,Sebolt-Leopold, Judith,Van Becelaere, Keri,Doherty, Annette M.,Kennedy, Robert M.,Marston, Dan,Howard Jr., W. Allen,Smith, Yvonne,Warmus, Joseph S.,Tecle, Haile
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supporting information; experimental part
p. 6501 - 6504
(2009/10/01)
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- Control of parasites in animals by the use of novel trifluoromethanesulfonanilide oxime ether derivatives
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Novel trifluoromethanesulfonanilide oxime ether compounds useful for controlling endo and/or ectoparasites in the environment are provided, together with methods of making the same, and methods of using the inventive compounds to treat parasite infestations in vivo or ex vivo.
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Page/Page column 26
(2010/10/20)
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