190446-85-6Relevant academic research and scientific papers
ALPHA-D-GALACTOPYRANOSIDE DERIVATIVES
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Page/Page column 65; 76, (2021/03/05)
The present invention relates to compounds of Formula (I) wherein Ar1, R1 and R2 are as described in the description, and A is 4,5-dihydroisoxazole-3,5-diyl, imidazolidin-4-one-l,3-diyl, oxazol-2- one-3,5-diyl and oxazolidine-2-one-3,5-diyl, l,2,3-triazole-l,4-diyl, isoxazole-3,5-diyl, imidazole-1, 4-diyl, and isothiazole-3,5-diyl; and their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of Formula (I), and especially to their use as Galectin-3 inhibitors.
Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator
Aicher, Thomas D.,Baer, Brian R.,Boyd, Steven A.,Chicarelli, Mark D.,Condroski, Kevin R.,DeWolf, Walter E.,Fischer, John,Frank, Michele,Hingorani, Gary P.,Hinklin, Ronald J.,Lee, Patrice A.,Neitzel, Nickolas A.,Pratt, Scott A.,Singh, Ajay,Sullivan, Francis X.,Turner, Timothy,Voegtli, Walter C.,Wallace, Eli M.,Williams, Lance
supporting information, (2019/12/24)
Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 72 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.
Stereospecific 1,4-Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes
Yang, Kai,Zhang, Feng,Fang, Tongchang,Zhang, Guan,Song, Qiuling
supporting information, p. 13421 - 13426 (2019/08/20)
Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.
A base promoted multigram synthesis of aminoisoxazoles: Valuable building blocks for drug discovery and peptidomimetics
Chalyk, Bohdan A.,Kandaurova, Inna Y.,Hrebeniuk, Kateryna V.,Manoilenko, Olga V.,Kulik, Irene B.,Iminov, Rustam T.,Kubyshkin, Vladimir,Tverdokhlebov, Anton V.,Ablialimov, Osman K.,Mykhailiuk, Pavel K.
, p. 25713 - 25723 (2016/03/25)
A practical multigram metal free synthesis of isoxazole-containing building blocks from commercially available amino acids was elaborated. The key reaction was a regioselective [3 + 2]-cycloaddition of in situ generated nitrile oxides with alkynes/enamines. The obtained building blocks were used in the preparation of bioactive compounds and peptidomimetics.
Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E
Keita, Massaba,Vandamme, Mathilde,Paquin, Jean-Fran?ois
, p. 3758 - 3766 (2015/11/28)
The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.
A practical and cost-efficient, one-pot conversion of aldehydes into nitriles mediated by 'activated DMSO'
Augustine, John Kallikat,Bombrun, Agnes,Atta, Rajendra Nath
experimental part, p. 2223 - 2227 (2011/10/31)
Participation of activated DMSO in the one-pot transformation of aldehydes to nitriles has been described by reacting aldehydes with NHHHCl in DMSO in the absence of any added base or catalyst. The method is applicable to access a wide range of aromatic, heterocyclic, and aliphatic nitriles, in which only water is a byproduct. A straightforward and practical procedure is demonstrated on a multigram scale. Georg Thieme Verlag Stuttgart - New York.
2-AMINOPYRIDINE ANALOGS AS GLUCOKINASE ACTIVATORS
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Page/Page column 48, (2008/12/04)
Provided are compounds that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.
2-AMINOPYRIDINE DERIVATIVES AS GLUCOKINASE ACTIVATORS
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Page/Page column 36, (2008/12/07)
Provided are compounds having the Formula (I) or salts thereof, wherein: L is O, S, SO, SO2, CHOH, C(O), or CH2; D2 is CR12 or N; R2 is aryl, heteroaryl, saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl (optionally substituted with oxo), wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl are monocyclic or bicyclic and are further optionally substituted with one or more groups independently selected from C1-C6 alkyl, F, Cl, Br, I, CF3, CN, OR6, C(=O)R6, C(=O)OR6, O(CH2)nC(=O)OR6, C(=O)NR6R7, NO2 and (1-6C alkyl)OR6; R3 is H, Br, OR6, SR6, C(O)OR6, C(O)NR6R7, C(O)R6, heteroaryl, or C1-C6 alkyl substituted with one or more groups independently selected from Vn-aryl, Vn-OR6, Vn- C(=O)OR6 and Vn-NR6R7; R11 is H or Cl; and R13 is N-(1 -6C alkanoyl)piperidin-4-yl; that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.
Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin- 1-yl-acetic acid antagonists of the human CCR5 chemokine receptor
Shankaran,Donnelly, Karla L.,Shah, Shrenik K.,Guthikonda, Ravindra N.,MacCoss, Malcolm,Mills, Sander G.,Gould, Sandra L.,Malkowitz, Lorraine,Siciliano, Salvatore J.,Springer, Martin S.,Carella, Anthony,Carver, Gwen,Hazuda, Daria,Holmes, Karen,Kessler, Joseph,Lineberger, Janet,Miller, Michael D.,Emini, Emilio A.,Schleif, William A.
, p. 3419 - 3424 (2007/10/03)
Efforts toward the exploration of the title compounds as CCR5 antagonists are disclosed. The basis for such work stems from the fact that cellular proliferation of HIV-1 requires the cooperative assistance of both CCR5 and CD4 receptors. The synthesis and SAR of pyrrolidineacetic acid derivatives as CCR5 antagonists displaying potent binding and antiviral properties in a HeLa cell-based HIV-1 infectivity assay are discussed.
Discovery of an orally active series of isoxazoline glycoprotein IIb/IIIa antagonists
Xue, Chu-Biao,Wityak, John,Sielecki, Thais M.,Pinto, Donald J.,Batt, Douglas G.,Cain, Gary A.,Sworin, Michael,Rockwell, Arlene L.,Roderick, John J.,Wang, Shuaige,Orwat, Michael J.,Frietze, William E.,Bostrom, Lori L.,Liu, Jie,Higley, C. Anne,Rankin, F. Wayne,Tobin, A. Ewa,Emmett, George,Lalka, George K.,Sze, Jean Y.,Di Meo, Susan V.,Mousa, Shaker A.,Thoolen, Martin J.,Racanelli, Adrienne L.,Hausner, Elizabeth A.,Reilly, Thomas M.,DeGrado, William F.,Wexler, Ruth R.,Olson, Richard E.
, p. 2064 - 2084 (2007/10/03)
Using isoxazoline XR299 (la) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions α and β to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u1,2 exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of the benzamidin-4-yl moiety with alternative basic groups, elimination of the isoxazoline stereocenter, and reversal of the orientation of the isoxazoline ring resulted in lowered potency and/or duration of action.
