Author: tianli

Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Chin, James En Wai; Liu, Xiaoping; Striepen, Boris; Makowska-Grzyska, Magdalena; Kim, Youngchang; Joachimiak, Andrzej; Hedstrom, Lizbeth; Cuny, Gregory D. published the artcile< Optimization of Benzoxazole-Based Inhibitors of Cryptosporidium parvum Inosine 5'-Monophosphate Dehydrogenase>, COA of Formula: C4H3NOS, the main research area is benzoxazole derivative preparation Cryptosporidium inosine monophosphate dehydrogenase inhibitor.

Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on IMP dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors vs. NAD+. The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochem. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative I demonstrated excellent CpIMPDH inhibitory activity (IC50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. The racemic version of I, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity vs. a wild-type T. gondii strain (200-fold). No toxicity was observed (LD50 > 50 μM) against a panel of four mammalian cells lines.

Journal of Medicinal Chemistry published new progress about Cryptosporidium parvum. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, COA of Formula: C4H3NOS.

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

Wang, Ning-Yu; Xu, Ying; Zuo, Wei-Qiong; Xiao, Kun-Jie; Liu, Li; Zeng, Xiu-Xiu; You, Xin-Yu; Zhang, Li-Dan; Gao, Chao; Liu, Zhi-Hao; Ye, Ting-Hong; Xia, Yong; Xiong, Ying; Song, Xue-Jiao; Lei, Qian; Peng, Cui-Ting; Tang, Hong; Yang, Sheng-Yong; Wei, Yu-Quan; Yu, Luo-Ting published the artcile< Discovery of Imidazo[2,1-b]thiazole HCV NS4B Inhibitors Exhibiting Synergistic Effect with Other Direct-Acting Antiviral Agents>, Computed Properties of 101080-15-3, the main research area is imidazothiazole HCV NS4B inhibitor drug synergism antiviral.

The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (I, EC50 = 16 nM) and 28g (II, EC50 = 31 nM). The resistance profile studies revealed that 26f and 28g targeted HCV NS4B, more precisely the second amphipathic α helix of NS4B (4BAH2). Cross-resistance between our 4BAH2 inhibitors and other direct-acting antiviral agents targeting NS3/4A, NS5A, and NS5B was not observed For the first time, the synergism of a series of combinations based on 4BAH2 inhibitors was evaluated. The results demonstrated that our 4BAH2 inhibitor 26f was synergistic with NS3/4A inhibitor simeprevir, NS5A inhibitor daclatasvir, and NS5B inhibitor sofosbuvir, and it could also reduce the dose of these drugs at almost all effect levels. Our study suggested that favorable effects could be achieved by combining 4BAH2 inhibitors such as 26f with these approved drugs and that new all-oral antiviral combinations based on 4BAH2 inhibitors were worth developing to supplement or even replace current treatment regimens for curing HCV infection.

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

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

Mallo-Abreu, Ana; Prieto-Diaz, Ruben; Jespers, Willem; Azuaje, Jhonny; Majellaro, Maria; Velando, Carmen; Garcia-Mera, Xerardo; Caamano, Olga; Brea, Jose; Loza, Maria I.; Gutierrez-de-Teran, Hugo; Sotelo, Eddy published the artcile< A Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists>, Computed Properties of 1003-32-3, the main research area is dihydrobenzoimidazopyrimidine carboxylate preparation SAR docking A2B adenosine receptor antagonist.

A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists was carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates I [R = H, cyclopentyl, Ph, etc.; R1 = Et, i-Pr], which contain 18 different pentagonal heterocyclic frameworks at position 4, was synthesized and evaluated. This study enabled the identication of new ligands that combine remarkable affinity (Ki < 30 nM) and exquisite selectivity. The SAR trends identified were substantiated by a mol. modeling study, based on a receptor-driven docking model and including a systematic free energy perturbation (FEP) study. Preliminary evaluation of the CYP3A4 and CYP2D6 inhibitory activity in optimized ligands evidenced weak and negligible activity resp. The stereospecific interaction between hA2BAR and the eutomer of the most attractive novel antagonist (S)-II (Ki = 3.66 nM) was validated. Journal of Medicinal Chemistry published new progress about Adenosine A2B receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Delaunay, Dominique; Toupet, Loiec; Corre, Maurice Le published the artcile< Reactivity of β-Amino Alcohols with Carbon Disulfide Study on the Synthesis of 2-Oxazolidinethiones and 2-Thiazolidinethiones>, Safety of (S)-4-Benzylthiazolidine-2-thione, the main research area is oxazolidinethione thiazolidinethione preparation.

Reaction of carbon disulfide with β-amino alcs. was examined to determine parameters directing the cyclization to oxazolidinethiones or thiazolidinethiones. By operating in mild conditions, i.e. in a low alk. medium, for a limited reaction time and in the presence of a stoichiometric quantity of CS2, oxazolidinethiones were preferentially obtained. On the other hand, thiazolidinethiones were prepared under drastic conditions by operating in a more basic medium, with an excess of CS2 and for a long reaction time. The formation of thiazolidinethiones occurred with an inversion of configuration of the carbon bearing the oxygen; furthermore, conversion of oxazolidinethiones into thiazolidinethiones was in some cases possible.

Journal of Organic Chemistry published new progress about Amino alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 171877-39-7 belongs to class thiazole, and the molecular formula is C10H11NS2, Safety of (S)-4-Benzylthiazolidine-2-thione.

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

Muthal, Bn published the artcile< Transition metal ion CoII, NiII, CuII & ZnII complexes of tridentate ligands (NNO) their synthesis, characterization and biological activities>, Formula: C9H7N3O2S, the main research area is nitrophenylthiazole hydroxybenzylideneimine transition metal Schiff base preparation antibacterial antifungal.

A series of new Schiff bases were synthesized by combination of 4(-3-nitrophenyl) thiazol-2-amine with hydroxy aldehyde (R-H, 5CH3 and 5Cl). Schiff bases and their transition metal complexes where characterized by elemental anal., UV-visible, IR spectra, magnetic susceptibility and conductivity measurement. The transition metal complexes are monomeric and 1:2 stoichem. having octahedral geometry. The ligands coordinated through oxygen atom of phenolic -OH group and also from thiazole ring nitrogen. The Schiff bases and their metal complexes were screen for antibacterial and antifungal activity.

Pharma Innovation published new progress about Antibacterial agents. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Formula: C9H7N3O2S.

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

Knoppova, V.; Antos, K.; Drobnica, L.; Kristian, P. published the artcile< Isothiocyanates. XXX. Synthesis, ultraviolet, and infrared spectra of 3-substituted rhodanines>, Application of C10H9NOS2, the main research area is rhodanine derivative IR UV.

Twenty-five rhodanine derivatives I (R = Me, Bu, p-BrC6H4, Ph, p-MeC6H4, 1-naphthyl, etc.) were prepared by treating the appropriate RNHCS2- or RNCS with ClCH2CO2H and HSCH2CO2H, resp. The products were characterized by uv absorptions at ∼250 and ∼290 nm, and an ir signal at 1725-1728 cm-1. The effect of substituents on the spectra was discussed.

Chemicke Zvesti published new progress about IR spectra. 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Application of C10H9NOS2.

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

Nakayama, Jun; Saito, Ryohei; Hayashi, Yusuke; Kitada, Nobuo; Tamaki, Shota; Han, Yuxuan; Semba, Kentaro; Maki, Shojiro A. published the artcile< High sensitivity in vivo imaging of cancer metastasis using a near-infrared luciferin analogue seMpai>, Application In Synthesis of 2591-17-5, the main research area is cancer metastasis IR luciferin analog sempai; in vivo imaging; luciferin analogue; metastasis; near-infrared bioluminescence.

Bioluminescence imaging (BLI) is useful to monitor cell movement and gene expression in live animals. However, D-luciferin has a short wavelength (560 nm) which is absorbed by tissues and the use of near-IR (NIR) luciferin analogs enable high sensitivity in vivo BLI. The AkaLumine-AkaLuc BLI system (Aka-BLI) can detect resolution at the single-cell level; however, it has a clear hepatic background signal. Here, to enable the highly sensitive detection of bioluminescence from the surrounding liver tissues, we focused on seMpai (C15H16N3O2S) which has been synthesized as a luciferin analog and has high luminescent abilities as same as AkaLumine. We demonstrated that seMpai BLI could detect micro-signals near the liver without any background signal. The solution of seMpai was neutral; therefore, seMpai imaging did not cause any adverse effect in mice. seMpai enabled a highly sensitive in vivo BLI as compared to previous techniques. Our findings suggest that the development of a novel mutated luciferase against seMpai may enable a highly sensitive BLI at the single-cell level without any background signal. Novel seMpai BLI system can be used for in vivo imaging in the fields of life sciences and medicine.

International Journal of Molecular Sciences published new progress about Bioluminescent imaging. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Application In Synthesis of 2591-17-5.

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

Ho, Duy-Khiet; LeGuyader, Clare; Srinivasan, Selvi; Roy, Debashish; Vlaskin, Vladimir; Chavas, Thomas E. J.; Lopez, Ciana L.; Snyder, Jessica M.; Postma, Almar; Chiefari, John; Stayton, Patrick S. published the artcile< Fully synthetic injectable depots with high drug content and tunable pharmacokinetics for long-acting drug delivery>, Name: 4,5-Dihydrothiazole-2-thiol, the main research area is pharmacokinetics drug delivery hydroxybenzyloxycarbonyl ethyloxycarbonyl methacrylate polymer; Drug delivery; HIV; Infectious disease; Long-acting depot; Polymer; Pre-exposure prophylaxis; RAFT; TAF.

Clin. studies have validated that antiretroviral (ARV) drugs can serve as an HIV pre-exposure prophylactic (PrEP) strategy. Dosing adherence remains a crucial factor determining the final efficacy outcomes, and both long-acting implants and injectable depot systems are being developed to improve patient adherence. Here, we describe an injectable depot platform that exploits a new mechanism for both formation and controlled release. The depot is a polymeric prodrug synthesized from monomers that incorporate an ARV drug tenofovir alafenamide (TAF) with degradable linkers that can be designed to control release rates. The prodrug monomers are synthetically incorporated into homopolymer or block designs that exhibit high drug weight percent (wt%) and also are hydrophobized in these prodrug segments to drive depot formation upon injection. Drug release converts those monomers to more hydrophilic pendant groups via linker cleavage, and as this drug release proceeds, the polymer chains losing hydrophobicity are then disassocd. from the depot and released over time to provide a depot dissolution mechanism. We show that long-acting TAF depots can be designed as block copolymers or as homopolymers. They can also be designed with different linkers, for example with faster or slower degrading p-hydroxybenzyloxycarbonyl (Benzyl) and ethyloxycarbonyl (Alkyl) linkers, resp. Diblock designs of p(glycerol monomethacrylate)-b-p(Alkyl-TAF-methacrylate) and p(glycerol monomethacrylate)-b-p(Benzyl-TAF-methacrylate) were first characterized in a mouse s.c. injection model. The alkylcarbamate linker design (TAF 51 wt%) showed excellent sustained release profiles of the key metabolite tenofovir (TFV) in skin and plasma over a 50-day period. Next, the homopolymer design with a high TAF drug wt% of 73% was characterized in the same model. The homopolymer depots with p(Alkyl-TAFMA) exhibited sustained TFV and TAF release profiles in skin and blood over 60 days, and TFV-DP concentrations in peripheral blood mononuclear cells (PBMC) were found to be at least 10-fold higher than the clin. suggested minimally EC90 protective concentration of 24 fmol/106 cells. These are the first reports of sustained parent TAF dosing observed in mouse and TFV-DP in mouse PBMC. IVIS imaging of rhodamine labeled homopolymer depots showed that degradation and release of the depot coincided with the sustained TAF release. Finally, these polymers showed excellent stability in accelerated stability studies over a six-month time period, and exceptional solubility of over 700 mg/mL in the DMSO formulation solvent. The homopolymer designs have a drug reservoir potential of well over a year at mg/day dosing and may not require cold chain storage for global health and developed world long-acting drug delivery applications.

Journal of Controlled Release published new progress about Chain transfer agents. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Name: 4,5-Dihydrothiazole-2-thiol.

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

Roosta, Atefeh; Alizadeh, Abdolali; Rezaiyehraad, Reze; Khanpour, Mojtaba published the artcile< Efficient and Chemoselective Procedure for Conversion of Rhodanine Derivatives into 1,3-Thiazolidine-2,4-diones via 1,3-Dipolar Cycloaddition Reaction and Rearrangement Sequences>, Recommanded Product: 3-Benzyl-2-thioxothiazolidin-4-one, the main research area is thiazolidinedione preparation chemoselective; alkalinity arylidene rhodanine preparation cycloaddition rearrangement.

A chemoselective 1,3-dipolar cycloaddition reaction between 5-alkylidene- or 5-arylidene rhodanine derivatives I (R1 = n-Pr, n-Bu, allyl, Bn; R2 = Ph, COOMe, 4-chloropheny, 4-methylpheny, 4-bromopheny) and nitrile oxide generated in situ from dibromoformaldoxime to construct 1,3-thiazolidine-2,4-diones II scaffold under mild conditions was reported. This strategy exhibits a distinguished manner to afford thiazolidine derivatives II in a simple, rapid and practical route. The results proved that the reaction proceeds through an unpredictable rearrangement and no spirocyclic product is generated. The structures of the target mols. were confirmed by IR, 1H NMR, 13C NMR, mass spectra and unambiguously X-ray crystal structure anal.

ChemistrySelect published new progress about 1,3-Dipolar cycloaddition reaction (chemoselective). 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Recommanded Product: 3-Benzyl-2-thioxothiazolidin-4-one.

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

Liang, Xiao; Fu, Huansheng; Xiao, Peng; Fang, Hao; Hou, Xuben published the artcile< Design, synthesis and biological evaluation of imidazolidine-2,4-dione and 2-thioxothiazolidin-4-one derivatives as lymphoid-specific tyrosine phosphatase inhibitors>, Name: 3-Benzyl-2-thioxothiazolidin-4-one, the main research area is thioxothiazolidinone preparation docking lymphoid tyrosine phosphatase inhibitor autoimmunity; imidazolidinedione preparation diastereoselective docking lymphoid tyrosine phosphatase inhibitor autoimmunity; Autoimmune diseases; Inhibitor; Lymphoid-specific tyrosine phosphatase.

Synthesized imidazolidine-2,4-dione derivatives I [R = carboxymethyl, Ph, benzyl, (4-carboxyphenyl)methyl, (4-phenylphenyl)methyl] and 2-thioxothiazolidin-4-one derivatives II (R1 = Bu, cyclohexyl, 2-chlorophenyl, thiazol-2-yl, etc.; R2 = carboxy, 4-carboxyphenyl, 2-carboxyeth-1-en-1-yl, etc.) as new LYP inhibitors were designed. Among them, the cinnamic acids-based inhibitors II [R1 = 2-methoxyphenyl, R2 = ((4-((1E)-2-carboxyeth-1-en-1-yl)phenyl)methyl)oxidanyl; R1 = 4-chlorophenyl, R2 = ((4-((1E)-2-carboxyeth-1-en-1-yl)phenyl)methyl)oxidanyl (III)] displayed good LYP inhibitory activities (IC50 = 2.85-6.95μM). Especially, the most potent inhibitor III was identified as competitive inhibitor (Ki = 1.09μM) and bind LYP reversibly. Meanwhile, III exhibited better selectivity over other phosphatases than known LYP inhibitor A15. Furthermore, compound III could regulate TCR associated signaling pathway in Jurkat T cell.

Bioorganic Chemistry published new progress about Aralkyl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Name: 3-Benzyl-2-thioxothiazolidin-4-one.

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