- Clickable transformation of nitriles (RCN) to oxazolyl sulfonyl fluoride warheads
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The protocol for simple, efficient, and mild synthesis of oxazolyl sulfonyl fluorides was developed through Rh2(OAc)4-catalyzed annulation of methyl-2-diazo-2-(fluorosulfonyl)acetate (MDF) or its ethyl ester derivative with nitriles. This practical method provides a general and direct route to a unique class of highly functionalized oxazolyl-decorated sulfonyl fluoride warheads with great potential in medicinal chemistry, chemical biology, and drug discovery.
- Fang, Wan-Yin,Wang, Shi-Meng,Zhang, Zai-Wei,Qin, Hua-Li
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supporting information
p. 8904 - 8909
(2020/11/30)
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- HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC CONDITIONS AND DISORDERS
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The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): (I), wherein L1, A, X1, X2, R1, R2, and R3 are described herein.
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Page/Page column 349; 350
(2018/03/25)
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- Olefination with Sulfonyl Halides and Esters: E-Selective Synthesis of Alkenes from Semistabilized Carbanion Precursors
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Carbanions of sulfonyl halides and activated sulfonates add to carbonyl compounds, and so-formed aldol-type adducts spontaneously fragment into olefins. This transformation mimics the one-pot Julia olefination with (hetero)aryl sulfones, but the mechanism of fragmentation involves a four-membered intermediate, typical for reactivity of phosphorus reagents. Moreover, in contrast to the reactions of sulfones, sulfonates of fluorinated alcohols (TFE and HFI) produce byproducts that are easily removed during workup. In our report, we focus on reactions of unstabilized and semistabilized carbanion precursors: alkylsulfonates, and allyl- and benzylsulfonates, respectively. In particular for semistabilized systems, olefins were synthesized as predominant E isomers in good yields. The presented studies reveal that optimal reaction conditions, including the type of base and alcohol groups of the sulfonates, are different depending on stabilization of the carbanion precursors and structure of the carbonyl substrates. The practical synthetic guide is supplemented with a discussion of the mechanism, based on reactivity studies of intermediates and identification of side-products.
- Górski, Bartosz,Basiak, Dariusz,Talko, Alicja,Basak, Tymoteusz,Mazurek, Tomasz,Barbasiewicz, Micha?
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supporting information
p. 1774 - 1784
(2018/04/27)
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- NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITIONS AND METHODS
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The invention relates to novel heteroaryl and heterocycle compounds of formula I and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune diseases and cancer.
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Paragraph 157
(2016/08/23)
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- Synthesis and cytotoxicity of novel 10-substituted dihydroartemisinin derivatives containing N-arylphenyl-ethenesulfonamide groups
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The manuscript describes the synthesis of 10-substituted dihydroartemisinin derivatives containing N-aryl phenylethenesulfonamide groups and their in vitro anti-tumor activities against the HT-29, MDA-MB-231, U87MG, H460, A549 and HL-60 cancer cell lines and the normal WI-38 cell line. Most tested compounds showed enhanced cytotoxic activities and good selectivity toward the MDA-MB-231, HT-29 and HL-60 cell lines, with IC50 values in the single-digit μM range as compared with dihydroartemisinin (DHA), and all of them displayed less toxicity towards WI-38 cells. Among them, compounds 3c and 6c with trifluoromethoxy groups on the N-phenyl ring were found to be most active compounds against the six tested cancer cell lines.
- Liu, Yajing,Liu, Zijian,Shi, Jiyue,Chen, Huimin,Mi, Bin,Li, Peng,Gong, Ping
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p. 2864 - 2877
(2013/05/09)
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- Design, synthesis, and biological evaluation of (E)-N-Aryl-2- arylethenesulfonamide analogues as potent and orally bioavailable microtubule-targeted anticancer agents
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A series of novel (E)-N-aryl-2-arylethenesulfonamides (6) were synthesized and evaluated for their anticancer activity. Some of the compounds in this series showed potent cytotoxicity against a wide spectrum of cancer cell-lines (IC50 values ranging from 5 to 10 nM) including all drug resistant cell-lines. Nude mice xenograft assays with compound (E)-N-(3-amino-4- methoxyphenyl)-2-(2′,4′,6′-trimethoxyphenyl)ethenesulfonamide (6t) showed dramatic reduction in tumor size, indicating their in vivo potential as anticancer agents. A preliminary drug development study with compound 6t is predicted to have increased blood-brain barrier permeability relative to many clinically used antimitotic agents. Mechanistic studies indicate that 6t and some other analogues disrupted microtubule formation, formation of mitotic spindles, and arrest of cells in mitotic phase. Compound 6t inhibited purified tubulin polymerization in vitro and in vivo and circumvented drug resistance mediated by P-glycoprotein. Compound 6t specifically competed with colchicine binding to tubulin and with similar avidity as podophylltoxin, indicating its binding site on tubulin.
- Reddy, M. V. Ramana,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Cosenza, Stephen C.,Billa, Vinay K.,Akula, Balaiah,Subbaiah, D. R. C. Venkata,Bharathi, E. Vijaya,Padgaonkar, Amol,Lv, Hua,Gallo, James M.,Reddy, E. Premkumar
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p. 5562 - 5586
(2013/07/26)
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- Design and synthesis of 2-substituted benzoxazoles as novel PTP1B inhibitors
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A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition. Compound 31d showed best biochemical potency (Ki) of 6.7 μM. Structure-activity relationship were explained with the help of molecular modeling approach.
- Chandrasekharappa, Arun P.,Badiger, Sangamesh E.,Dubey, Pramod K.,Panigrahi, Sunil K.,Manukonda, Sekhar Reddy V.V.V.
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supporting information
p. 2579 - 2584
(2013/06/27)
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- Metal-free, radical addition to alkenes via desulfitative chlorine atom transfer
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An efficient method for radical additions to unactivated alkenes via desulfitative chlorine-atom transfer is described. The reaction is based on the use of readily available sulfonyl chlorides as starting materials and cheap radical initiators such as azobisisobutyronitrile (AIBN), di-tert-butyldiazene (DTBD), and dilauroyl peroxide (DLP). No transition metal catalyst is required and the reaction takes place under mild conditions at temperatures °C. Copyright
- Cao, Lidong,Weidner, Karin,Renaud, Philippe
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supporting information; experimental part
p. 3467 - 3472
(2012/02/03)
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- Efficient carboazidation of alkenes using a radical desulfonylative azide transfer process
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The radical-mediated carboazidation of terminal alkenes using electrophilic alkanesulfonyl azides is reported. A single reagent delivers the necessary electrophilic alkyl radical as well as the azido group, and good yields are obtained by using a moderate excess of the carboazidating reagent (1.5-2 equiv). Interestingly, in addition to the starting sulfonyl azide, this method requires only the use of a radical initiator, di-tert-butyldiazene. In terms of atom economy, this azide transfer reaction is close to ideal, as SO2 (1 equiv) is the only side product. The synthetic potential of this process has been demonstrated by a formal synthesis of the alkaloid lepadiformine C.
- Weidner, Karin,Giroult, Andre,Panchaud, Philippe,Renaud, Philippe
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supporting information; experimental part
p. 17511 - 17515
(2011/02/23)
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- NOVEL MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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The embodiments provide compounds of the general Formulae I, II, III, IV, V, VI, VII, and X, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
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- δ-Sultone formation through Rh-catalyzed C-H insertion
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Rhodium-catalyzed reactions of sulfonate ester derivatives are biased strongly toward 1,6-insertion and thus offer a general method for assembling δ-sultones. Two protocols for staging this cyclization reaction are described, which capitalize on the unique ability of either diazo or iodonium ylide intermediates to form Rh-carbene species. The value of these heterocycles for fine chemicals synthesis is demonstrated in both reductive and oxidative reactions that make possible excision of the -SO3- moiety.
- Wolckenhauer, Scott A.,Devlin, A. Sloan,Du Bois
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p. 4363 - 4366
(2008/03/11)
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- Pyridyl-containing spirocyclic compounds as inhibitors of fibrinogen-dependent platelet aggregation
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Disclosed are certain substituted or unsubstituted pyridyl-containing spirocyclic compounds substituted with both basic and acidic functionality, which are useful in inhibiting platelet aggregation, inhibiting the binding of fibrinogen to blood platelets, and preventing or treating thrombosis
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- Inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT) as hypocholesterolemic agents: Synthesis and structure-activity relationships of novel series of sulfonamides, acylphosphonamides and acylphosphoramidates
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Sulfoacetic acid, phosphoramidate, and phosphonamide analogs of the ACAT inhibitors, CI-999 and CI-1011 were synthesized. The structure-activity relationships of these compounds as ACAT inhibitors are described.
- Lee,Roark,Picard,Sliskovic,Roth,Stanfield,Hamelehle,Bousley,Krause
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p. 289 - 294
(2007/10/03)
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- β-carboxy sulfonamide ACAT inhibitors
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β-Carboxy sulfonyl compounds of the formula STR1 wherein R1 is aryl, R3 is hydrogen or alkyl, R3 and R4 are hydrogen or alkyl, Y is --O--, --S--, or --NR2 --, and R5 is alkyl or aryl are potent inhibitors of the enzyme acyl CoA:cholesterol acyltransferase (ACAT) and are thus useful for treating hypercholesterolemia and atherosclerosis.
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- Sulfonate ACAT inhibitors
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β-Carboxy sulfonates of the formula STR1 wherein R1 is aryl, R3 and R4 are hydrogen or alkyl, Y is -O-, -S-, or -NR2 -, and R5 is alkyl or aryl are potent inhibitors of the enzyme acyl CoA:cholesterol acyltransferase (ACAT) and are thus useful for treating hypercholesterolemia and atherosclerosis.
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