Heterocyclic Building Blocks-Benzoxazole

Frings, Marcus’s team published research in European Journal of Medicinal Chemistry in 2017-01-27 | CAS: 50578-18-2

Sulfoximines from a Medicinal Chemist’s Perspective: Physicochemical and in vitro Parameters Relevant for Drug Discovery. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/1621962-30-8.html, 145026-07-9

1-Iminotetrahydrothiophene 1-oxide (BD00963737) is a building block containing a sulfoximine group. Several CDK and ATR inhibitors have exemplified the utilization of the NH sulfoximine group as abioisostere for a sulfonamide group to overcome the main project hurdles of aqueous solubility, sulfonamide-mediated off-target activity and IP. Moreover, its NH group could be expediently further functionalized through Buchwald-Hartwig coupling reaction and multifarious nucleophilic reactions.. Recommended Products is: 4381-25-3 and 83730-53-4.

Sulfoximines, sulfondiimides and sulfonimidamides are fascinating but not yet fully explored variants of the common sulfone or sulfonamide motif. In this study, we report the physicochem. and in vitro properties of sulfoximines and compare them with related analogs and isosteres. Furthermore, we present a matched mol. pair anal. of compounds from drug discovery projects within Boehringer Ingelheim. We demonstrate that the sulfoximine moiety is a chem. stable, comparatively polar and weakly basic functional group, often leading to favorable aqueous solubility, permeability and metabolic stability. Moreover, their addnl. vectors at nitrogen enable simple chem. modifications and thus facilitate exploration and fine-tuning of the mol. properties. We conclude that sulfoximines and their congeners do not exhibit any intrinsic flaw but significantly enrich the toolbox of medicinal chemists.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Xu, Qianhe’s team published research in Biochimica et Biophysica Acta, Molecular Cell Research in 2022-10-31 | CAS: 83730-53-4

Revealing PACMA 31 as a new chemical type TrxR inhibitor to promote cancer cell apoptosis. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

(2S)-2-Amino-4-(butylsulfonimidoyl)butanoic acid (BD136012) is a building block containing a sulfoximine group. Several CDK and ATR inhibitors have exemplified the utilization of the NH sulfoximine group as abioisostere for a sulfonamide group to overcome the main project hurdles of aqueous solubility, sulfonamide-mediated off-target activity and IP. Moreover, its NH group could be expediently further functionalized through Buchwald-Hartwig coupling reaction and multifarious nucleophilic reactions.. Recommended Products is: 4381-25-3 and 1621962-30-8.

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis, while dysregulation of redox homeostasis is a hallmark for cancer cells. Thus, there is considerable potential to inhibit the aberrantly upregulated TrxR in cancer cells to discover selective cancer therapeutic agents. Nevertheless, the structural types of TrxR inhibitors presented currently are still relatively limited. We herein report that PACMA 31, previously reported to inhibit protein disulfide isomerase (PDI), is a potent TrxR inhibitor. PACMA 31 possesses a pharmacophore scaffold that is structurally different from the announced TrxR inhibitors and exhibits effective cytotoxicity against cervical cancer cells. Our results reveal that PACMA 31 selectively inhibits TrxR over the related glutathione reductase (GR) and in the presence of reduced glutathione (GSH). Further studies with mutant enzyme and mol. docking suggest that the propynamide fragment of PACMA 31 interacts covalently with the selenocysteine residue of TrxR. Moreover, PACMA 31 effectively and selectively curbs TrxR activity in cells and further stimulates the production of reactive oxygen species (ROS) at low micromolar concentrations, which in turn triggers the accumulation of oxidized thioredoxin (Trx) and GSSG in cells. Follow-up studies demonstrate that PACMA 31 targets TrxR in cells to induce oxidative stress-mediated cancer cell apoptosis. Our results provide a new structural type of TrxR inhibitor that may serve as a useful probe for investigating the biol. of TrxR-implicated pathways, and uncover a new target of PACMA 31 that contributes to it becoming a candidate for cancer treatment.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Romero, Rodrigo’s team published research in Nature Cancer in 2020-06-02 | CAS: 83730-53-4

Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Approx. 20-30% of human lung adenocarcinomas (LUADs) harbor mutations in Kelch-like ECH-associated protein 1 (KEAP1) that hyperactivate the nuclear factor, erythroid 2-like 2 (NFE2L2) antioxidant program. We previously showed that Kras-driven Keap1-mutant LUAD is highly aggressive and dependent on glutaminolysis. Here we performed a druggable genome CRISPR screen and uncovered a Keap1-mutant-specific dependency on solute carrier family 33 member 1 (Slc33a1), as well as several functionally related genes associated with the unfolded protein response. Genetic and biochem. experiments using mouse and human Keap1-mutant tumor lines, as well as preclin. genetically engineered mouse models, validate Slc33a1 as a robust Keap1-mutant-specific dependency. Furthermore, unbiased genome-wide CRISPR screening identified addnl. genes related to Slc33a1 dependency. Overall, our study provides a rationale for stratification of patients harboring KEAP1-mutant or NRF2-hyperactivated tumors as likely responders to targeted SLC33A1 inhibition and underscores the value of integrating functional genetic approaches with genetically engineered mouse models to identify and validate genotype-specific therapeutic targets.

Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Lohier, Jean-Francois’s team published research in Chemical Communications (Cambridge, United Kingdom) in 2017 | CAS: 50578-18-2

Mechanistic investigation of the NH-sulfoximination of sulfide. Evidence for ¦Ë6-sulfanenitrile intermediates. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/1621962-30-8.html, 145026-07-9

We report a new procedure for the preparation of NH-sulfoximines from sulfides using PIDA as an oxidant and ammonium carbamate as the ammonia source. Excellent yields were obtained with a wide range of sulfides. The formation of acetoxy- and methoxy-¦Ë6-sulfanenitrile as intermediates was proposed, both of which were converted to the NH-sulfoximine by the action of the solvent. The structure of these intermediates was confirmed by 1H, 13C and 15N NMR and HRMS anal.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Hendriks, Christine M. M.’s team published research in Advanced Synthesis & Catalysis in 2014 | CAS: 145026-07-9

N-Alkylations of NH-sulfoximines and NH-sulfondiimines with alkyl halides mediated by potassium hydroxide in dimethyl sulfoxide. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/1621962-30-8.html, 50578-18-2

1-Bromo-4-(S-methylsulfonimidoyl)benzene (BD336512) is a building block containing a sulfoximine group. Several CDK and ATR inhibitors have exemplified the utilization of the NH sulfoximine group as abioisostere for a sulfonamide group to overcome the main project hurdles of aqueous solubility, sulfonamide-mediated off-target activity and IP. Moreover, its NH group could be expediently further functionalized through Buchwald-Hartwig coupling reaction and multifarious nucleophilic reactions.. Recommended Products is: 4381-25-3 and 83730-53-4.

A general method for the N-alkylation of NH-sulfoximines and NH-sulfondiimines has been developed, employing alkyl bromides with KOH in DMSO at room temperature A variety of previously inaccessible N-alkylated sulfoximines and sulfondiimines was prepared in good to excellent yields (up to 97%). As an application, the conditions were used to access the biol. active Suloxifen.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Rajbongshi, Kamal K.’s team published research in Synthesis in 2020-04-30 | CAS: 50578-18-2

Microwave-Accelerated N-Acylation of Sulfoximines with Aldehydes under Catalyst-Free Conditions. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/1621962-30-8.html, 145026-07-9

An efficient catalyst-free radical cross-coupling reaction between sulfoximines R1S(O)(=NH)R2 [R1 = Me, Ph, 4-methoxyphenyl, 4-bromophenyl; R2 = Me, Ph; R1R2 = -(CH2)4-] and aromatic aldehydes R3CHO (R3 = 2-chlorophenyl, naphthalen-1-yl, furan-2-yl, etc.) was developed. The reaction took place in the presence of N-bromosuccinimide as the radical initiator under microwave irradiation to afford the corresponding acylated sulfoximines R1S(O)(R2)=NC(O)R3 in moderate to excellent yields (27 examples). This protocol is proved to be rapid, easy to handle, and applicable to a broad scope of substrates.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Schumacher, Christian’s team published research in Organic Chemistry Frontiers in 2020 | CAS: 4381-25-3

N-(2,3,5,6-Tetrafluoropyridyl)sulfoximines: synthesis, X-ray crystallography, and halogen bonding. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

(S-Methylsulfonimidoyl)benzene (BD302898) is a building block containing a sulfoximine group. Several CDK and ATR inhibitors have exemplified the utilization of the NH sulfoximine group as abioisostere for a sulfonamide group to overcome the main project hurdles of aqueous solubility, sulfonamide-mediated off-target activity and IP. Moreover, its NH group could be expediently further functionalized through Buchwald-Hartwig coupling reaction and multifarious nucleophilic reactions.. Recommended Products is: 83730-53-4 and 1621962-30-8.

In the presence of KOH, NH-sulfoximines react with pentafluoropyridine to give N-(tetrafluoropyridyl)sulfoximines (NTFP-sulfoximines) I (R1 = Me, Ph, 4-MeC6H4, 4-ClC6H4, etc.; R = Me, i-Pr, 2-Py, 2-thiophenyl, etc.; ) in moderate to excellent yields. Either a solution-based or a superior solvent-free mechanochem. protocol can be followed. X-Ray diffraction analyses of 26 products provided insight into the bond parameters and conformational rigidity of the mol. scaffold. In solid-state structures, sulfoximines with halo substituents on the S-bound arene are intermolecularly linked by C-X¡¤¡¤¡¤O=S (X = Cl, Br) halogen bonds. Hirshfeld surface anal. is used to assess the type of non-covalent contacts present in mols. For mixtures of three different S-pyridyl-substituted NTFP-sulfoximines and N-iodosuccinimide (NIS) in CDCl3, association constants were determined by 1H NMR spectroscopy. The data revealed a dependence of the halogen bond strength on the position of the pyridyl nitrogen indicating the presence of N-I¡¤¡¤¡¤N(S-pyridyl) interactions. Neither the S=O oxygen nor the tetrafluoropyridyl-substituted nitrogen of the sulfoximine appeared to be involved in halogen bonding.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Sharma, Nidhi’s team published research in RSC Advances in 2016 | CAS: 50578-18-2

Palladium nanoparticles catalyzed aroylation of NH-sulfoximines with aryl iodides. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/1621962-30-8.html, 145026-07-9

A novel approach towards aroylation of NH-sulfoximines using Pd nanoparticles stabilized by a binaphthyl backbone (Pd-BNP) was developed. This synthetic protocol involved the Pd-BNP promoted carbon monoxide insertion of aryl iodides to form an aroyl intermediate which further reacted with NH-sulfoximines to form N-aroyl sulfoximine derivatives in good to excellent yields. The Pd-BNP catalyst was recovered and reused up to six times.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Altenburg, Bianca’s team published research in ACS Medicinal Chemistry Letters in 2020-10-08 | CAS: 4381-25-3

Chiral Analogues of PFI-1 as BET Inhibitors and Their Functional Role in Myeloid Malignancies. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Structural analogs of PFI-1 varying at the sulfur core were prepared, and their activities as BET inhibitors in myeloid cell lines and primary cells from patients with acute myeloid leukemia were studied. Docking calculations followed by mol. dynamics simulations revealed the binding mode of the newly prepared inhibitors, suggesting explanations for the observed high enantiospecificity of the inhibitory activity.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Guan, Xin’s team published research in Advanced Functional Materials in 2020-07-06 | CAS: 83730-53-4

Tumor Metabolism-Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron-Hole Pairs’ Separation. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Reactive oxygen species (ROS) depletion and low ROS production that result from the intratumoral redox metabolism equilibrium and low energy conversion efficiency from ultrasound mech. energy to ROS-represented chem. energy, resp., are two vital inhibitory factors of sonodynamic therapy (SDT). To address the two concerns, a tumor metabolism-engineered composite nanoplatform capable of intervening intratumoral ROS metabolism, breaking the redox equilibrium, and reshaping the tumor microenvironment is constructed to reinforce SDT against tumors. In this metabolism-engineered nanoplatform, Nb2C nanosheets serve as the scaffold to accommodate TiO2 sonosensitizers and L-buthionine-sulfoximine. Systematic experiments show that such nanoplatforms can reduce ROS depletion via suppressing glutathione synthesis and simultaneously improving ROS production via the Nb2C-enhanced production and separation of electron-hole pairs. Contributed by the combined effect, net ROS content can be significantly elevated, which results in the highly efficient anti-tumor outcomes in vivo and in vitro. Moreover, the combined design principles, i.e., tumor metabolism modulation for reducing ROS depletion and electron-hole pair separation for facilitating ROS production, can be extended to other ROS-dependent therapeutic systems.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem