Category: 1003-32-3

Dessi, Alessio; Calamante, Massimo; Mordini, Alessandro; Zani, Lorenzo; Taddei, Maurizio; Reginato, Gianna published the artcile< Microwave-activated synthesis of thiazolo[5,4-d]thiazoles by a condensation/oxidation sequence>, Synthetic Route of 1003-32-3, the main research area is thiazolothiazole microwave preparation condensation oxidation.

A microwave-assisted preparation of sym. thiazolo[5,4-d]thiazoles from the corresponding aldehydes is presented. The two-step reaction sequence comprises the condensation of aldehydes with dithiooxamide followed by oxidation/aromatization with 1,4-benzoquinone derivatives The new procedure provides the desired products in good yields and in most cases allows reduction of the excess of aldehyde employed in the process compared to previous methodologies. For the first time, application of the reaction both on aromatic and aliphatic aldehydes is demonstrated.

RSC Advances published new progress about Aliphatic aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Synthetic Route of 1003-32-3.

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

Ospanov, Meirambek; Sulochana, Suresh P.; Paris, Jason J.; Rimoldi, John M.; Ashpole, Nicole; Walker, Larry; Ross, Samir A.; Shilabin, Abbas G.; Ibrahim, Mohamed A. published the artcile< Identification of an Orally Bioavailable, Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor>, Safety of Thiazole-5-carboxyaldehyde, the main research area is pyrrolobenzodiazepine preparation neuroinflammation cannabinoid receptor antineurodegenerative activity pharmacokinetic property; cannabinoid receptors CB1/CB2; central nervous system (CNS); neurodegenerative diseases; neuroinflammation; pharmacokinetics (PK); pyrrolobenzodiazepines; radioligand binding assay.

Modulation of the endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiol. processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines tricyclic chemotype with a high conformational similarity in comparison to the existing leads. These compounds are structurally unique, confirming their chemotype novelty. In our continuing search for new chemotypes as selective CB2 regulatory mols., following SAR approaches, a total of 17 selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs were synthesized and tested for their ability to bind to the CB1 and CB2 receptor orthosteric sites. A competitive [3H]CP-55,940 binding screen revealed five compounds that exhibited >60% displacement at 10 μM concentration Further concentration-response anal. revealed two compounds, 4k and 4q, as potent and selective CB2 ligands with sub-micromolar activities (Ki = 146 nM and 137 nM, resp.). In order to support the potential efficacy and safety of the analogs, the oral and i.v. pharmacokinetic properties of compound 4k were sought. Compound 4k was orally bioavailable, reaching maximum brain concentrations of 602 ± 162 ng/g (p.o.) with an elimination half-life of 22.9 ± 3.73 h. Whether administered via the oral or i.v. route, the elimination half-lives ranged between 9.3 and 16.7 h in the liver and kidneys. These compounds represent novel chemotypes, which can be further optimized for improved affinity and selectivity toward the CB2 receptor.

Molecules published new progress about Anti-neurodegenerative agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Safety of Thiazole-5-carboxyaldehyde.

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

Valente, Sergio; Mellini, Paolo; Spallotta, Francesco; Carafa, Vincenzo; Nebbioso, Angela; Polletta, Lucia; Carnevale, Ilaria; Saladini, Serena; Trisciuoglio, Daniela; Gabellini, Chiara; Tardugno, Maria; Zwergel, Clemens; Cencioni, Chiara; Atlante, Sandra; Moniot, Sebastien; Steegborn, Clemens; Budriesi, Roberta; Tafani, Marco; Del Bufalo, Donatella; Altucci, Lucia; Gaetano, Carlo; Mai, Antonello published the artcile< 1,4-Dihydropyridines Active on the SIRT1/AMPK Pathway Ameliorate Skin Repair and Mitochondrial Function and Exhibit Inhibition of Proliferation in Cancer Cells>, Safety of Thiazole-5-carboxyaldehyde, the main research area is preparation dihydropyridine sirtuin AMPK antitumor neoplasm.

Modulators of sirtuins are considered promising therapeutic targets for the treatment of cancer, cardiovascular, metabolic, inflammatory, and neurodegenerative diseases. Here we prepared new 1,4-dihydropyridines (DHPs) bearing changes at the C2/C6, C3/C5, C4, or N1 position. Tested with the SIRTainty procedure, some of them displayed increased SIRT1 activation with respect to the prototype 3a, high NO release in HaCat cells, and ameliorated skin repair in a mouse model of wound healing. In C2C12 myoblasts, two of them improved mitochondrial d. and functions. All the effects were reverted by coadministration of compound C (9), an AMPK inhibitor, or of EX-527 (10), a SIRT1 inhibitor, highlighting the involvement of the SIRT1/AMPK pathway in the action of DHPs. Finally, tested in a panel of cancer cells, the water-soluble form of 3a, compound 8, displayed antiproliferative effects in the range of 8-35 μM and increased H4K16 deacetylation, suggesting a possible role for SIRT1 activators in cancer therapy.

Journal of Medicinal Chemistrypublished new progress about Antitumor agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Safety of Thiazole-5-carboxyaldehyde.

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

Zhao, Xin; Li, Runfeng; Zhou, Yang; Xiao, Mengjie; Ma, Chunlong; Yang, Zhongjin; Zeng, Shaogao; Du, Qiuling; Yang, Chunguang; Jiang, Haiming; Hu, Yanmei; Wang, Kefeng; Mok, Chris Ka Pun; Sun, Ping; Dong, Jianghong; Cui, Wei; Wang, Jun; Tu, Yaoquan; Yang, Zifeng; Hu, Wenhui published the artcile< Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses>, Electric Literature of 1003-32-3, the main research area is preparation antiviral pinanamine derivative resistant influenza A virus.

Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure-activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor M090 against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that M090 targets influenza HA and it occupied a highly conserved pocket of the HA2 domain and inhibited virus-mediated membrane fusion by “”locking”” the bending state of HA2 during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development.

Journal of Medicinal Chemistrypublished new progress about Antiviral agent resistance. 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

O’Connor, Stephen J.; Barr, Kenneth J.; Wang, Le; Sorensen, Bryan K.; Tasker, Andrew S.; Sham, Hing; Ng, Shi-Chung; Cohen, Jerome; Devine, Edward; Cherian, Sajeev; Saeed, Badr; Zhang, Haichao; Lee, Jang Yun; Warner, Robert; Tahir, Stephen; Kovar, Peter; Ewing, Patricia; Alder, Jeffrey; Mitten, Michael; Leal, Juan; Marsh, Kennan; Bauch, Joy; Hoffman, Daniel J.; Sebti, Said M.; Rosenberg, Saul H. published the artcile< Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy>, Electric Literature of 1003-32-3, the main research area is peptidomimetic preparation protein farnesyltransferase inhibitor antitumor; protein farnesyltransferase inhibitor peptidomimetic structure antitumor; antitumor agent peptidomimetic protein farnesyltransferase inhibitor.

The synthesis and evaluation of analogs of previously reported farnesyltransferase inhibitors, a pyridyl benzyl ether and a pyridylbenzylamine, are described. Substitution of the pyridyl benzyl ether at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of the pyridylbenzylamine at the benzyl nitrogen yielded 4-(N-benzyl-N-3-pyridylaminomethyl)-2-(2-methylphenyl)benzoylmethionine (I), which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 4-(N-3,5-difluorobenzyl-N-phenylaminomethyl)-2-(2-methylphenyl)benzoylmethionine, which demonstrated a dramatically improved pharmacokinetic profile. I and 4-(N-benzyl-N-phenylaminomethyl)-2-(2-methylphenyl)benzoylmethionine demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Journal of Medicinal Chemistrypublished new progress about Antitumor agents. 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

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>, HPLC of Formula: 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 Chemistrypublished 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, HPLC of Formula: 1003-32-3.

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

Jaffett, Victor A.; Nerurkar, Alok; Cao, Xufeng; Guzei, Ilia A.; Golden, Jennifer E. published the artcile< Telescoped synthesis of C3-functionalized (E)-arylamidines using Ugi-Mumm and regiospecific quinazolinone rearrangements>, Safety of Thiazole-5-carboxyaldehyde, the main research area is arylamidine stereoselective preparation; azidobenzoic acid isocyanide aldehyde bismethylaminoethane Ugi Mumm regiospecific rearrangement.

An efficient four-step, six-transformation protocol was developed to afford bioactive N-alkyl- or N-arylamide (E)-arylamidines I (R1 = Cy, 4-OMeC6H4, i-Pr, etc.; R2 = i-Pr, i-Bu, H, etc.; R3 = H, 5-CH3, 5-F, etc.) featuring strategic amidine C3 modifications which were inaccessible or low yielding by previous methods. This synthetic approach, exemplified with 24 amidines and requiring only a single purification, highlights a multicomponent Ugi-Mumm rearrangement to afford highly diversified quinazolinones which undergo regiospecific rearrangement to afford new amidines. The method extensively broadens the structural scope of this new class of trisubstituted amidines and demonstrates the tolerance of regional C3 amidine steric bulk, visualized with X-ray crystallog. anal.

Organic & Biomolecular Chemistrypublished new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Safety of Thiazole-5-carboxyaldehyde.

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

Yin, Liuyan; Wang, Lanzhi published the artcile< Chemo-/regio-selective synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines using Lewis acid, CeCl3·7H2O>, Application of C4H3NOS, the main research area is dihydrobenzodiazepine aryl acetyl preparation chemoselective regioselective; phenylenediamine aryl aldehyde butynone condensation Lewis acid catalyst.

A unique and efficient method has been developed for the one-pot synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines I (Ar = 2-thiazolyl, 2-thienyl, 4-ClC6H4, etc.) in good yields using o-phenylenediamine, aromatic aldehyde and 3-butyn-2-one in the presence of a catalytic amount of CeCl3·7H2O in ethanol at ambient temperature An exclusive chemo-/regio-selective formation of substituted isomers of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines II (Ar = 2-thiazolyl, 2-thienyl, 4-ClC6H4, etc.; R = CH3, F, Cl, Br) was achieved from the different reaction process, by exploiting the strategy based on the variation of electrophilicity of the two electrophilic centers of aromatic aldehyde, 3-butyn-2-one and nucleophilic profiles of substituted o-phenylenediamines. This process offers an easy and efficient synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines in high yields.

Tetrahedron Letterspublished new progress about Aryl aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application of C4H3NOS.

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

Isbrandt, Eric S.; Nasim, Amrah; Zhao, Karen; Newman, Stephen G. published the artcile< Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is aryl iodide aldehyde nickel diazadiphosphacyclooctane catalyst reductive Heck arylation; primary alc aryliodide nickel diazadiphosphacyclooctane catalyst reductive Heck arylation; secondary alc preparation.

A catalytic method to access secondary alcs. by the coupling of aryl iodides was reported. Either aldehydes or alcs. can be used as reaction partners, making the transformation reductive or redox-neutral, resp. The reaction was mediated by a Ni catalyst and a 1,5-diaza-3,7-diphosphacyclooctane. This P2N2 ligand, which was previously been unrecognized in cross-coupling and related reactions, was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs. An interrupted carbonyl-Heck type mechanism was proposed to be operative, with a key 1,2-insertion step forging the new C-C bond and forming a nickel alkoxide that may be turned over by an alc. reductant. The same catalyst was also found to enable synthesis of ketone products from either aldehydes or alcs., demonstrating control over the oxidation state of both the starting materials and products.

Journal of the American Chemical Societypublished new progress about Aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 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

Tao, Zhi-Fu; Chen, Zehan; Bui, Mai-Ha; Kovar, Peter; Johnson, Eric; Bouska, Jennifer; Zhang, Haiying; Rosenberg, Saul; Sowin, Thomas; Lin, Nan-Horng published the artcile< Macrocyclic ureas as potent and selective Chk1 inhibitors: An improved synthesis, kinome profiling, structure-activity relationships, and preliminary pharmacokinetics>, HPLC of Formula: 1003-32-3, the main research area is macrocyclic urea preparation selective Chk1 inhibitor; structure macrocyclic urea selectivity Chk1 inhibitor pharmacokinetics; doxorubicin macrocyclic urea combination antitumor activity; kinase selectivity inhibition macrocyclic urea; amine protection key step preparation macrocyclic urea; trimethylsilylethoxycarbonyl group protection amine key step preparation macrocyclic urea.

Macrocyclic ureas such as I [R = H, H2N, MeNH, Me2N, (HOCH2CH2)2N, HOCH2CH2NH, 5-thiazolylmethylamino, 4-pyridinecarbonylamino, 2-chloro-4-pyridinecarbonylamino, (S)-MeCH(NH2)CONH, 2-(4-morpholinyl)ethoxycarbonylamino, 2-oxo-3-oxazolidinyl, HO, HOCH2CH2O, HO(CH2)3O, MeO(CH2)3, 2-(4-morpholinyl)ethoxy, 3-(4-morpholinyl)propoxy, 4-(1-piperidinyl)-1-piperidinecarbonyloxy, (HO)2P(:O); X = CH2CH2, CH:CH] are prepared as selective Chk1 kinase inhibitors and as agents for the sensitization of tumor cells to doxorubicin for potential use as anticancer agents. The structure-activity relationship for Chk1 inhibition of substituted 14-membered urea macrocycles is determined, leading to the identification of sixteen compounds which are effective inhibitors of Chk1. The active urea macrocycles significantly sensitize tumor cells to the DNA-damaging antitumor agent doxorubicin in a cell-based assay and efficiently abrogate the doxorubicin-induced G2/M and camptothecin-induced S checkpoints. The inhibition of a panel of 120 kinases by I (R = 5-thiazolemethylamino; X = CH2CH2; II) is determined; II inhibits Chk1 at 100-fold lower concentrations than any of the other kinases in the panel. Pharmacokinetic studies of I (R = H; X = CH2CH2, CH2CH2CH2) suggest that 14-membered macrocycles such as I (R = H; X = CH2CH2) may possess better pharmacokinetic properties than their 15-membered counterparts such as I (R = H; X = CH2CH2CH2). An improved method for the preparation of amine-containing urea macrocycles I [R = H2N; X = CH:CH, CH2CH2] is determined; protection of the free amino group of a bisallyl diaryl urea intermediate with the trimethylsilylethoxycarbonyl group allows ring-closing macrocyclocondensation in the presence of the Hoveyda-Grubbs catalyst without the formation of inseparable and highly colored byproducts.

Bioorganic & Medicinal Chemistry Letterspublished new progress about Antitumor agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, HPLC of Formula: 1003-32-3.

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