50765-70-3

Usage

InChI:InChI=1/C10H14O5S/c1-8-2-4-10(5-3-8)16(13,14)15-7-9(12)6-11/h2-5,9,11-12H,6-7H2,1H3/t9-/m0/s1

Upstream product

• 109371-30-4 (S)-2-benzyloxy-3-(toluene-4-sulfonyloxy)-propan-1-ol 
• 98-59-9 p-toluenesulfonyl chloride 
• 15028-30-5 D-1-Benzyl-3-tosylglycerol 
• 139884-57-4 <(S)-2-(allyloxy)trimethylene> valerate p-toluenesulfonate 
• 138850-84-7 (S)-1-O-Tosyl-2-O-benzyl-3-O-methoxymethylglycerol 
• 104768-03-8 (-)-2,3-O-<(R)-Benzyliden>-5-O-(p-toluolsulfonyl)-D-ribonsaeure-γ-lacton 
• 51704-66-6 (+/-)-2,3-dihydroxypropyl tosylate 
• 40519-00-4 2,3-O-Isopropylidene-5-O-(p-tolylsulfonyl)-D-ribono-1,4-lactone 
• 4873-09-0 allyl tosylate 
• 23735-43-5 (S)-1-O-tosyl-2,3-O-isopropylideneglycerol 
• 89174-50-5 (R)-glycerol acetonide 
• 141656-30-6 (R)-(+)-3-tosyloxypropane-1,2-diol dipropionate 
• 141656-36-2 Propionic acid (S)-2-hydroxy-3-(toluene-4-sulfonyloxy)-propyl ester 
• 119970-97-7 (+)-5-O-(p-Toluolsulfonyl)-D-ribonsaeure-γ-lacton 

Downstream Products

• 99291-25-5 levodropropizine 
• 134071-44-6 ((2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)methyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate 
• 134071-44-6 ((2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)methyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate 
• 82966-35-6 (2S,4S)-cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<<(4-methylphenyl)sulfonyl>oxy>methyl>-1,3-dioxolane 
• 82966-35-6 (2R,4S)-trans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-<<<(4-methylphenyl)sulfonyl>oxy>methyl>-1,3-dioxolane 

Relevant academic research and scientific papers

Design and Synthesis of Tetrazole- And Pyridine-Containing Itraconazole Analogs as Potent Angiogenesis Inhibitors

Itraconazole, a widely used antifungal drug, was found to possess antiangiogenic activity and is currently undergoing multiple clinical trials for the treatment of different types of cancer. However, it suffers from extremely low solubility and strong interactions with many drugs through inhibition of CYP3A4, limiting its potential as a new antiangiogenic and anticancer drug. To address these issues, a series of analogs in which the phenyl group is replaced with pyridine or fluorine-substituted benzene was synthesized. Among them the pyridine- and tetrazole-containing compound 24 has significantly improved solubility and reduced CYP3A4 inhibition compared to itraconazole. Similar to itraconazole, compound 24 inhibited the AMPK/mTOR signaling axis and the glycosylation of VEGFR2. It also induced cholesterol accumulation in the endolysosome and demonstrated binding to the sterol-sensing domain of NPC1 in a simulation study. These results suggested that compound 24 may serve as an attractive candidate for the development of a new generation of antiangiogenic drug.

MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE

The present disclosure provides for compounds of Formula (I) wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

Macrocyclic MCL-1 inhibitors and methods of use

The present disclosure provides for compounds of Formula (I) wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

MACROCYCLIC MCL-1 INHIBITORS AND METHODS OF USE

The present disclosure provides for compounds of formula (I), wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of formula (I).

SMALL MOLECULE INHIBITORS OF FIBROSIS

Described herein are compounds and compositions for the treatment of a fibrotic disease.

Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic

Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold.

Asymmetric synthesis and effect of absolute stereochemistry of YCZ-2013, a brassinosteroid biosynthesis inhibitor

The four stereoisomers of 2RS,4RS-1-[[2-(2,4-dichlorophenyl)-4-(2-(2- propenyloxy)phenoxymethyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (YCZ-2013), a novel brassinosteroid biosynthesis inhibitor, were prepared. The diastereomers of 2RS,4R-5 and 2RS,4S-5 were prepared by using the corresponding optically pure R and S toluene-4-sulfonic acid 2,3-dihydroxypropyl ester (R-4,S-4). The enatiomerically and diastereomerically pure acetonide (5) was obtained by a method involving diastereoselective crystallisation of the tosylate salt, followed by re-equilibration with the mother liquor and chromatography. The optical purity of four target compounds (YCZ-2013) was confirmed by chiral high-performance liquid chromatography (HPLC) and NMR. The effects of these stereoisomers on Arabidopsis stem elongation indicated that the cis isomers of 2S,4R-YCZ-2013 and 2R,4S-YCZ-2013 exhibited potent inhibitory activity with IC50 values of approximately 24 ± 3 and 24 ± 2 nM, respectively. The IC50 values of the trans isomers of 2S,4S-YCZ-2013 and 2R,4R-YCZ-2013 are approximately 1510 ± 50 and 3900 ± 332 nM, respectively. Co-application of brassinolide (10 nM), the most potent BR, and GA3 (1 μM) to Arabidopsis seedlings grown in the dark with 2R,4S-YCZ-2013 and 2S,4R-YCZ-2013 revealed that brassinolide recovered the induced dwarfism of Arabidopsis seedlings, whereas GA3 showed no effect.

Mild, versatile, and chemoselective indium(III) triflate-catalyzed deprotection of acetonides under microwave heating conditions

A series of acetonides (both terminal and internal isopropylidene acetals) have been deprotected under catalytic, neutral conditions to give their corresponding 1,2-diols. The reactions utilize indium(III) triflate in the presence of water and an organic solvent with mild microwave heating. Terminal acetonides are chemoselectivley removed in the presence of internal acetonides; acid labile functional groups remain intact under these conditions, thereby greatly enhancing the scope of the reaction substrates that can be utilized with this approach.

Assignment of the stereochemistry of spiroxamine by two-dimensional NMR spectroscopy and stereoselective chemical synthesis

Spiroxamine is a new powdery mildew fungicide in cereals consisting of four biologically active isomers (two diastereomers, four enantiomers). The four isomers were separated by preparative high-performance liquid chromatography (HPLC) on a chiral stationary phase. At this stage it was not possible to assign their stereochemistry. Using stereoselective synthesis starting with the corresponding chirally pure glycerol derivates, the configuration at the asymmetric center, could be fixed. The resulting diastereomers were separated by preparative HPLC. Using COSY, HSQC and NOESY NMR spectroscopy it was possible to assign the configuration of the amino residue relative to the cyclohexyl ring. The 600 MHz 1H NMR spectra permitted a complete assignment of all proton signals. The stereochemical assignment is based on NOEs observed in the NOESY spectrum.

Eine neue Ligandenklasse fuer die asymmetrische Dihydroxylierung von Olefinen

Keywords: Asymmetrische Dihydroxylierungen; Chirale Liganden; Chinchonaalkaloide; Katalyse; Osmiumverbindungen