- The synthesis of novel disorazoles
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Big little brother: The simplified disorazole analogue 1 exhibits its cytotoxic activity at low nanomolar concentrations and provides selectivities not observed for the parent natural product.
- Schaeckel, Romy,Hinkelmann, Bettina,Sasse, Florenz,Kaiesse, Markus
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- POLYMYXIN ANALOGS USEFUL AS ANTIBIOTIC POTENTIATORS
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The disclosure provides compounds of the formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of either of the foregoing. The variables A, R1, and R2 are defined in the disclosure. The disclosure further includes pharmaceutical compositions comprising a compound of formula I together with at least one pharmaceutically acceptable carrier. The disclosure also includes a method of sensitizing bacteria to an antibacterial agent, comprising administering to a patient infected with the bacteria, simultaneously or sequentially, a therapeutically effective amount of the antibacterial agent and a compound of formula (I).
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Paragraph 0149
(2017/12/09)
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- PYRROLE ANTIFUNGAL AGENTS
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The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof; wherein: R1, R2, R3, R4, R5, R6, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 152
(2009/12/05)
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- Oxidative rearrangements of isobenzofurans: Studies toward the synthesis of the ajudazols
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(Chemical Equation Presented) We present a new facet of isobenzofuran chemistry which allows for its efficient manipulation to generate biologically relevant entities. This methodology has been successfully applied toward the synthesis of ajudazol A.
- Hobson, Stephen J.,Parkin, Andrew,Marquez, Rodolfo
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supporting information; experimental part
p. 2813 - 2816
(2009/05/27)
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- Large-scale preparation of 2-methyloxazole-4-carboxaldehyde
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The large-scale preparation of 2-methyloxazole-4-carboxaldehyde presents a significant challenge due to the physical characteristics of the molecule. A method for the preparation of 10-kg batches of 2-methyloxazole-4-carboxaldehyde is described. The key reaction is the reduction of the corresponding N-methoxy-N-methyl amide using lithium aluminium hydride, followed by workup and isolation by crystallization.
- Benoit, Georges-Emmanuel,Carey, John S.,Chapman, Alan M.,Chima, Ranjit,Hussain, Nigel,Popkin, Matthew E.,Roux, Guillaume,Tavassoli, Bahareh,Vaxelaire, Carine,Webb, Michael R.,Whatrup, David
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- Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol- 4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications
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Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.
- Iso, Yasuyoshi,Grajkowska, Ewa,Wroblewski, Jarda T.,Davis, Jared,Goeders, Nicholas E.,Johnson, Kenneth M.,Sanker, Subramaniam,Roth, Bryan L.,Tueckmantel, Werner,Kozikowski, Alan P.
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p. 1080 - 1100
(2007/10/03)
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- Synthesis of 4-arylethynyl-2-methyloxazole derivatives as mGluR5 antagonists for use in the treatment of drug abuse
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In structure-activity relationship studies directed toward the use of mGluR5 antagonists in the treatment of drug abuse, we sought a convenient means for gaining access to the oxazole analogues of MTEP. Toward this end, the aldehyde group in 2-methyloxazo
- Iso, Yasuyoshi,Kozikowski, Alan P.
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p. 243 - 246
(2007/10/03)
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- Oxidation of oxazolines and thiazolines to oxazoles and thiazoles. Application of the Kharasch-Sosnovsky reaction
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Using a modification of the Kharasch-Sosnovsky reaction, the oxidation of oxazolines and thiazolines bearing a variety of 2-alkyl substituents (chiral and achiral) were smoothly oxidized to their corresponding oxazoles and thiazoles, respectively. The key feature involved in the successful implementation of this important oxidation was the use of a mixture of Cu(I) and Cu(II) salts to enhance the oxidation of the intermediate captodative radical, 24. The main limitation of this method was shown when the oxidation failed with oxazolines/thiazolines lacking the carboalkoxy group at C-4.
- Meyers,Tavares, Francis X.
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p. 8207 - 8215
(2007/10/03)
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