Category: 73303-88-5

Bandarage, Upul K. published the artcileNitrosothiol esters of diclofenac: synthesis and pharmacological characterization as gastrointestinal-sparing prodrugs, Application of 2-Methyl-2-sulfanylpropan-1-ol, the publication is Journal of Medicinal Chemistry (2000), 43(21), 4005-4016, database is CAplus and MEDLINE.

Despite its widespread use, diclofenac has gastrointestinal liabilities common to nonsteroidal antiinflammatory drugs (NSAIDs) that might be reduced by concomitant administration of a gastrointestinal cytoprotectant such as nitric oxide (NO). A series of novel diclofenac esters containing a nitrosothiol (-S-NO) moiety as a NO donor functionality has been synthesized and evaluated in vivo for bioavailability, pharmacol. activity, and gastric irritation. All S-NO-diclofenac derivatives acted as orally bioavailable prodrugs, producing significant levels of diclofenac in plasma within 15 min after oral administration to mice. At equimolar oral doses, S-NO-diclofenac derivatives I [R = R’ = Me, Et, RR’ = (CH₂)₅] and II (n = 2, 3) displayed rat antiinflammatory and analgesic activities comparable to those of diclofenac in the carrageenan-induced paw edema test and the mouse phenylbenzoquinone-induced writhing test, resp. All tested S-NO-diclofenac derivatives I and II were gastric-sparing in that they elicited markedly fewer stomach lesions as compared to the stomach lesions caused by a high equimolar dose of diclofenac in the rat. Nitrosothiol esters of diclofenac comprise a novel class of NO-donating compounds having therapeutic potential as nonsteroidal antiinflammatory agents with an enhanced gastric safety profile.

Journal of Medicinal Chemistry published new progress about 73303-88-5. 73303-88-5 belongs to alcohols-buliding-blocks, auxiliary class Thiol,Aliphatic hydrocarbon chain,Alcohol, name is 2-Methyl-2-sulfanylpropan-1-ol, and the molecular formula is C4H10OS, Application of 2-Methyl-2-sulfanylpropan-1-ol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Pei, Zhonghua published the artcileExploration of Pyrrolobenzodiazepine (PBD)-Dimers Containing Disulfide-Based Prodrugs as Payloads for Antibody-Drug Conjugates, Quality Control of 73303-88-5, the publication is Molecular Pharmaceutics (2018), 15(9), 3979-3996, database is CAplus and MEDLINE.

A number of cytotoxic pyrrolobenzodiazepine (PBD) monomers containing various disulfide-based prodrugs were evaluated for their ability to undergo activation (disulfide cleavage) in vitro in the presence of either glutathione (GSH) or cysteine (Cys). A good correlation was observed between in vitro GSH stability and in vitro cytotoxicity toward tumor cell lines. The prodrug-containing compounds were typically more potent against cells with relatively high intracellular GSH levels (e.g., KPL-4 cells). Several antibody-drug conjugates (ADCs) were subsequently constructed from PBD dimers that incorporated selected disulfide-based prodrugs. Such HER2 conjugates exhibited potent antiproliferation activity against KPL-4 cells in vitro in an antigen-dependent manner. However, the disulfide prodrugs contained in the majority of such entities were surprisingly unstable toward whole blood from various species. One HER2-targeting conjugate that contained a thiophenol-derived disulfide prodrug was an exception to this stability trend. It exhibited potent activity in a KPL-4 in vivo efficacy model that was approx. three-fold weaker than that displayed by the corresponding parent ADC. The same prodrug-containing conjugate demonstrated a three-fold improvement in mouse tolerability properties in vivo relative to the parent ADC, which did not contain the prodrug.

Molecular Pharmaceutics published new progress about 73303-88-5. 73303-88-5 belongs to alcohols-buliding-blocks, auxiliary class Thiol,Aliphatic hydrocarbon chain,Alcohol, name is 2-Methyl-2-sulfanylpropan-1-ol, and the molecular formula is C4H10OS, Quality Control of 73303-88-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Pillow, Thomas H. published the artcileAntibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity, Application of 2-Methyl-2-sulfanylpropan-1-ol, the publication is ChemMedChem (2020), 15(1), 17-25, database is CAplus and MEDLINE.

The ability to selectively degrade proteins with bifunctional small mols. has the potential to fundamentally alter therapy in a variety of diseases. However, the relatively large size of these chimeric mols. often results in challenging physico-chem. properties (e. g., low aqueous solubility) and poor pharmacokinetics which may complicate their in vivo applications. We recently discovered an exquisitely potent chimeric BET degrader (GNE-987) which exhibited picomolar cell potencies but also demonstrated low in vivo exposures. In an effort to improve the pharmacokinetic properties of this mol., we discovered the first degrader-antibody conjugate by attaching GNE-987 to an anti-CLL1 antibody via a novel linker. A single IV dose of the conjugate afforded sustained in vivo exposures that resulted in antigen-specific tumor regressions. Enhancement of a chimeric protein degrader with poor in vivo properties through antibody conjugation thereby expands the utility of directed protein degradation as both a biol. tool and a therapeutic possibility.

ChemMedChem published new progress about 73303-88-5. 73303-88-5 belongs to alcohols-buliding-blocks, auxiliary class Thiol,Aliphatic hydrocarbon chain,Alcohol, name is 2-Methyl-2-sulfanylpropan-1-ol, and the molecular formula is C4H10OS, Application of 2-Methyl-2-sulfanylpropan-1-ol.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts