Month: October 2022

Fushimi, Makoto; Buck, Hannes; Balbach, Melanie; Gorovyy, Anna; Ferreira, Jacob; Rossetti, Thomas; Kaur, Navpreet; Levin, Lonny R.; Buck, Jochen; Quast, Jonathan; van den Heuvel, Joop; Steegborn, Clemens; Finkin-Groner, Efrat; Kargman, Stacia; Michino, Mayako; Foley, Michael A.; Miller, Michael; Liverton, Nigel J.; Huggins, David J.; Meinke, Peter T. published the artcile< Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10)>, Computed Properties of 1003-32-3, the main research area is adenylyl cyclase inhibitor oral bioavailability.

Soluble adenylyl cyclase (sAC) has gained attention as a potential therapeutic target given the role of this enzyme in intracellular signaling. We describe successful efforts to design improved sAC inhibitors amenable for in vivo interrogation of sAC inhibition to assess its potential therapeutic applications. This work culminated in the identification of TDI-10229 (12), which displays nanomolar inhibition of sAC in both biochem. and cellular assays and exhibits mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound

ACS Medicinal Chemistry Letters published new progress about Drug design. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Computed Properties of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Siegel, David J.; Anderson, Grace I.; Paul, Lauren M.; Seibert, Philipp J.; Hillesheim, Patrick C.; Sheng, Yinghong; Zeller, Matthias; Taubert, Andreas; Werner, Peter; Balischewski, Christian; Michael, Scott F.; Mirjafari, Arsalan published the artcile< Design Principles of Lipid-like Ionic Liquids for Gene Delivery>, Recommanded Product: 4,5-Dihydrothiazole-2-thiol, the main research area is ionic liquid gene delivery amphiphile lipid; DNA delivery; biomaterials; cationic lipids; gene therapy; ionic liquids; lipid-like materials; nonviral vectors.

We developed lipid-like ionic liquids, containing 2-mercaptoimidazolium and 2-mercaptothiazolinium headgroups tethered to two long saturated alkyl chains, as carriers for in vitro delivery of plasmid HEK DNA into 293T cells. We employed a combination of modular design, synthesis, X-ray anal., and computational modeling to rationalize the self-assembly and desired physicochem. and biol. properties. The results suggest that thioamide-derived ionic liquids may serve as a modular platform for lipid-mediated gene delivery. This work represents a step toward understanding the structure-function relationships of these amphiphiles with long-range ordering and offering insight into design principles for synthetic vectors based on self-assembly behavior.

ACS Applied Bio Materials published new progress about Amphiphiles. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Recommanded Product: 4,5-Dihydrothiazole-2-thiol.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Nakajima, Kanako; Hamada, Kazuko; Ito, Ryoga; Yoshida, Yukina; Sutherland, Kenneth; Ishikawa, Masayori; Ozaki, Michitaka; Shirato, Hiroki; Hamada, Toshiyuki published the artcile< Stability of -luciferin for bioluminescence to detect gene expression in freely moving mice for long durations>, Product Details of C11H8N2O3S2, the main research area is Dluciferin L luciferin antiobesity agent obesity cancer; Period1; circadian rhythm; in vivo imaging; luciferin.

Circadian disturbance of clock gene expression is a risk factor for diseases such as obesity, cancer, and sleep disorders. To study these diseases, it is necessary to monitor and analyze the expression rhythm of clock genes in the whole body for a long duration. The bioluminescent reporter enzyme firefly luciferase and its substrate -luciferin have been used to generate optical signals from tissues in vivo with high sensitivity. However, little information is known about the stability of -luciferin to detect gene expression in living animals for a long duration. In the present study, we examined the stability of a luciferin solution over 21 days. -Luciferin, which is synthesized using racemization of -luciferin, was at high concentrations after 21 days. In addition, we showed that bioluminescence of Period1 (Per1) expression in the liver was significantly decreased compared with the day 1 solution, although locomotor activity rhythm was not affected. These results showed that -luciferin should be applied to the mouse within, at most, 7 days to detect bioluminescence of Per1 gene expression rhythm in vivo.

Luminescence published new progress about Acyl-CoA-binding proteins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Product Details of C11H8N2O3S2.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Patel, Bhargav A.; Abel, Biebele; Barbuti, Anna Maria; Velagapudi, Uday Kiran; Chen, Zhe-Sheng; Ambudkar, Suresh V.; Talele, Tanaji T. published the artcile< Comprehensive Synthesis of Amino Acid-Derived Thiazole Peptidomimetic Analogues to Understand the Enigmatic Drug/Substrate-Binding Site of P-Glycoprotein>, Safety of Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate, the main research area is thiazole peptidomimetic synthesis ATPase stimulator inhibitor structure activity; drug substrate binding P glycoprotein antitumor agent mol docking; peptide coupling Boc protection.

A novel set of 64 analogs based on our lead compound (I) was designed and synthesized with an initial objective of understanding the structural requirements of ligands binding to a highly perplexing substrate-binding site of P-gp and their effect on modulating the ATPase function of the efflux pump. Compound I, a stimulator of P-gp ATPase activity, was transformed to ATPase inhibitory compounds (II), (III) and (IV). The ATPase inhibition by these compounds was predominantly contributed by the presence of a cyclohexyl group in lieu of the 2-aminobenzophenone moiety of I. The 4,4-difluorocyclohexyl analogs III and IV inhibited the photolabeling by [125I]-IAAP, with IC50 values of 0.1 and 0.76 M, resp. Selected compounds were shown to reverse paclitaxel resistance in HEK293 cells overexpressing P-gp and were selective toward P-gp over CYP3A4. Induced-fit docking highlighted a plausible binding pattern of inhibitory compounds in the putative-binding pocket of P-gp. The current study underscores the stringent requirement by P-gp to bind to chem. similar mols.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Safety of Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

L’abbe, Gerrit; Yu, Chih-Chou published the artcile< Trapping of thiaziridinimines with thiocarbonyl compounds>, Formula: C10H9NOS2, the main research area is thiaziridinimine thiocarbonyl trap; dithiazolidine spirothiazolidine; thiazolidine spirodithiazolidine; thiatriazoline thermolysis; dithiazolidinimine.

Thermolysis of 4-benzyl-5-tosylimino-1,2,3,4-thiatriazoline (I; Ts = 4-MeC6H4SO2) at 60-70° in the presence of representative C=S unsaturated compounds furnished 1,2,4-dithiazolidin-5-imines in moderate yields. An intermediate unstable thiaziridinimine which is trapped by the C=S compound in a regiospecific manner is postulated. Among the thiocarbonyl compounds used are p,p’-dimethoxythiobenzophenone, xanthates and 3-benzylrhodanine, the latter giving a spiro adduct II.

Journal of Heterocyclic Chemistry published new progress about 10574-69-3. 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Formula: C10H9NOS2.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Murty, Surya; Haile, Samuel T.; Beinat, Corinne; Aalipour, Amin; Alam, Israt S.; Murty, Tara; Shaffer, Travis M.; Patel, Chirag B.; Graves, Edward E.; Mackall, Crystal L.; Gambhir, Sanjiv S. published the artcile< Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model>, HPLC of Formula: 2591-17-5, the main research area is disialoganglioside GD2 CAR T cell apoptosis glioblastoma; Chimeric antigen receptor (CAR); glioblastoma; imaging; immunotherapy; intravital microscopy.

Recent advances in novel immune strategies, particularly chimeric antigen receptor (CAR)-bearing T-cells, have shown limited efficacy against glioblastoma (GBM) in clin. trials. We currently have an incomplete understanding of how these emerging therapies integrate with the current standard of care, specifically radiation therapy (RT). Addnitionally, there is an insufficient number of preclin. studies monitoring these therapies with high spatiotemporal resolution To address these limitations, we report the first longitudinal fluorescence-based intravital microscopy imaging of CAR T-cells within an orthotopic GBM preclin. model to illustrate the necessity of RT for complete therapeutic response. Complete antitumor response in advanced syngeneic orthotopic models of GBM was achieved only when a single i.v. dose of GD2 CAR T-cells was following either sub-lethal whole-body irradiation or focal RT. Intravital microscopy imaging successfully visualized CAR T-cell homing and T-cell mediated apoptosis of tumor cells in real-time within the tumor stroma. Findings indicate that RT allows for rapid CAR T-cell extravasation from the vasculature and expansion within the tumor microenvironment. These exciting results highlight potential opportunities to improve IV adoptive T-cell administration in the treatment of GBM through concurrent RT. Addnl., they emphasize the need for advancements in immunotherapeutic homing to and extravasation through the tumor microenvironment.

OncoImmunology published new progress about Apoptosis. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, HPLC of Formula: 2591-17-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Sparey, Tim; Abeywickrema, Pravien; Almond, Sarah; Brandon, Nick; Byrne, Noel; Campbell, Alister; Hutson, Pete H.; Jacobson, Marlene; Jones, Brian; Munshi, Sanjeev; Pascarella, Danette; Pike, Andrew; Prasad, G. Sridhar; Sachs, Nancy; Sakatis, Melanie; Sardana, Vinod; Venkatraman, Shankar; Young, Mary Beth published the artcile< The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors>, Electric Literature of 1003-32-3, the main research area is fused pyrrole carboxylate preparation aminoacid oxidase DAO inhibitor structure; schizophrenia fused pyrrole carboxylic acid DAO inhibitor.

The NMDA hypofunction hypothesis of schizophrenia’ can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of D-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma D-serine levels after dosing i.p. to rats. In parallel, analogs were prepared to survey the SARs of 1.

Bioorganic & Medicinal Chemistry Letters published new progress about Antipsychotics. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Electric Literature of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ching, Kuan-Chieh; Tran, Thi Ngoc Quy; Amrun, Siti Naqiah; Kam, Yiu-Wing; Ng, Lisa F. P.; Chai, Christina L. L. published the artcile< Structural Optimizations of Thieno[3,2-b]pyrrole Derivatives for the Development of Metabolically Stable Inhibitors of Chikungunya Virus>, Quality Control of 1003-32-3, the main research area is thieno pyrrole derivative preparation metabolic stability Chikungunya Virus antiviral.

Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus, and there is no approved effective antiviral treatment currently available for CHIKV. We previously reported the discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activity against CHIKV infection in vitro. However, it has a short half-life in the presence of human liver microsomes (HLMs) (T1/2 = 2.91 min). Herein, we report further optimization studies in which potential metabolically labile sites on compound 1b were removed or modified, resulting in the identification of thieno[3,2-b]pyrrole 20 and pyrrolo[2,3-d]thiazole 23c possessing up to 17-fold increase in metabolic half-lives in HLMs and good in vivo pharmacokinetic properties. Compound 20 not only attenuated viral RNA production and displayed broad-spectrum antiviral activity against other alphaviruses and CHIKV isolates but also exhibited limited cytotoxic liability (CC50 > 100 μM). These studies have identified two compounds that have the potential for further development as antiviral drugs against CHIKV infection.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Quality Control of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Stachulski, Andrew V.; Pidathala, Chandrakala; Row, Eleanor C.; Sharma, Raman; Berry, Neil G.; Iqbal, Mazhar; Bentley, Joanne; Allman, Sarah A.; Edwards, Geoffrey; Helm, Alison; Hellier, Jennifer; Korba, Brent E.; Semple, J. Edward; Rossignol, Jean-Francois published the artcile< Thiazolides as Novel Antiviral Agents. 1. Inhibition of Hepatitis B Virus Replication>, Formula: C6H10N2S, the main research area is thiazolide preparation Hepatitis replication inhibition antiviral human structure activity.

The syntheses and activities of a wide range of thiazolides [viz., 2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis B virus replication, with results of QSAR anal. are reported. The prototypical thiazolide, nitazoxanide [2-hydroxybenzoyl-N-(5-nitrothiazol-2-yl)amide, NTZ] I, is a broad spectrum antiinfective agent effective against anaerobic bacteria, viruses, and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide II is a novel, potent, and selective inhibitor of hepatitis B replication (EC50 = 0.33 μm) but is inactive against anaerobes. Several 4′- and 5′-substituted thiazolides show good activity against HBV; by contrast, some related salicyloylanilides show a narrower spectrum of activity. The ADME properties of II are similar to I, viz., the O-acetate is an effective prodrug, and the O-aryl glucuronide is a major metabolite. The QSAR study shows a good correlation of observed EC90 for intracellular virions with thiazolide structural parameters. Finally the mechanism of action of thiazolides in relation to the present results is discussed.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 101080-15-3 belongs to class thiazole, and the molecular formula is C6H10N2S, Formula: C6H10N2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Qian, Yuanyuan; Allegretta, Giuseppe; Janardhanan, Jeshina; Peng, Zhihong; Mahasenan, Kiran V.; Lastochkin, Elena; Gozun, Melissa Malia N.; Tejera, Sara; Schroeder, Valerie A.; Wolter, William R.; Feltzer, Rhona; Mobashery, Shahriar; Chang, Mayland published the artcile< Exploration of the Structural Space in 4(3H)-Quinazolinone Antibacterials>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is quinazolinone preparation antibacterial pharmacokinetic SAR staphylococcus aureus QSAR.

Herein the syntheses of 79 derivatives of the 4(3H)-quinazolinones and their structure-activity relationship (SAR) against methicillin-resistant Staphylococcus aureus (MRSA) is reported. Twenty-one analogs were further evaluated in in vitro assays. Subsequent investigation of the pharmacokinetic properties singled out compound I ((E)-3-(5-carboxy-2-fluorophenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one) for further study. The compound synergized with piperacillin-tazobactam (TZP) both in vitro and in vivo in a clin. relevant mouse model of MRSA infection. The TZP combination lacks activity against MRSA, yet it synergized with compound I to kill MRSA in a bactericidal manner. The synergy is rationalized by the ability of the quinazolinones to bind to the allosteric site of penicillin-binding protein (PBP)2a, resulting in opening of the active site, whereby the β-lactam antibiotic now is enabled to bind to the active site in its mechanism of action. The combination effectively treats MRSA infection, for which many antibiotics (including TZP) have faced clin. obsolescence.

Journal of Medicinal Chemistry published new progress about Antibacterial agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Recommanded Product: Thiazole-5-carboxyaldehyde.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica