Category: 1003-32-3

Kirubakaran, Sivapriya; Gorla, Suresh Kumar; Sharling, Lisa; Zhang, Minjia; Liu, Xiaoping; Ray, Soumya S.; MacPherson, Iain S.; Striepen, Boris; Hedstrom, Lizbeth; Cuny, Gregory D. published the artcile< Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is benzimidazole inhibitor Cryptosporidium parvum IMPDH preparation SAR antiparasitic activity.

Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via IMP dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Herein is reported a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.

Bioorganic & Medicinal Chemistry Letters published new progress about Cryptosporidiosis. 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

Hagen, Susan E.; Domagala, John; Gajda, Christopher; Lovdahl, Michael; Tait, Bradley D.; Wise, Eric; Holler, Tod; Hupe, Donald; Nouhan, Carolyn; Urumov, Andrej; Zeikus, Greg; Zeikus, Eric; Lunney, Elizabeth A.; Pavlovsky, Alexander; Gracheck, Stephen J.; Saunders, James; VanderRoest, Steve; Brodfuehrer, Joanne published the artcile< 4-Hydroxy-5,6-dihydropyrones as inhibitors of HIV protease: the effect of heterocyclic substituents at C-6 on antiviral potency and pharmacokinetic parameters>, Category: thiazole, the main research area is hydroxydihydropyrone HIV protease inhibitor antiviral agent.

Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, the authors previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable back-up candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocycle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymic and cellular tests) and low cellular toxicity; furthermore, several analogs exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailability was (S)-3-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (I). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, I was chosen for further preclin. evaluation.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Category: thiazole.

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

Huang, Zhi-Xing; Yu, Jia-Hui; Xu, Xing-Jun; Xu, Xiao-Fang; Zeng, Ting; Lin, Jing; Chen, Wei-Min published the artcile< Cajaninstilbene acid analogues as novel quorum sensing and biofilm inhibitors of Pseudomonas aeruginosa>, HPLC of Formula: 1003-32-3, the main research area is Pseudomonas aeruginosa Cajaninstilbene acid analog quorum sensing biofilm inhibitor; Anti-Biofilm; Cajaninstilbene acid; Pseudomonas aeruginosa; Quorum sensing regulator.

Biofilm formation and virulence factor secretion in opportunistic pathogen Pseudomonas aeruginosa are essential for establishment of chronic and recurrent infection, which are regulated by quorum sensing (QS) system. In this study, a set of cajaninstilbene acid analogs were designed and synthesized, and their abilities to inhibit QS and biofilm formation were investigated. Among all the compounds, compounds 3g, 3m and 3o showed potent anti-biofilm activity, especially 3o exhibited promising biofilm inhibitory activity with biofilm inhibition ratio of 49.50 ± 1.35% at 50 μM. Three lacZ reporter strains were constructed to identify the effects of compound 3o on different QS systems. Compound 3o showed the suppression on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors. Therefore, compound 3o is expected to be generated as a lead compound with inhibition of biofilm formation and QS of Pseudomonas aeruginosa.

Microbial Pathogenesis published new progress about Microbial gene, lacZ 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

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

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

Ulmschneider, Sarah; Modduller-Vieira, Ursula; Klein, Christian D.; Antes, Iris; Lengauer, Thomas; Hartmann, Rolf W. published the artcile< Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase. [Erratum to document cited in CA142:373650]>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is erratum heteroarylidene aromatic compound stereoisomer preparation aldosterone oxidase inhibition; pyridylmethylene tetrahydronaphthalene indane stereoisomer preparation aldosterone oxidase inhibition erratum; structure heteroarylidene aromatic compound stereoisomer aldosterone oxidase inhibition erratum; CYP11B2 inhibiting heteroarylidene aromatic compound stereoisomer preparation erratum; selective aldosterone oxidase inhibiting heteroarylidene aromatic compound erratum; mol modeling heteroarylidene aromatic compound binding CYP11B1 CYP11B2 erratum.

In Tables 2 and 3 on pages 1567 and 1568, the column of values for the % inhibition for human CYP17 and the columns of values for IC50 for V79 11B1 hCP11B1 and V79 11B2 hCYP11B2 were switched. The correct versions of the tables are given.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 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

Roe, Caroline; Hobbs, Heather; Stockman, Robert A. published the artcile< Multicomponent synthesis of chiral sulfinimines>, Reference of 1003-32-3, the main research area is chiral sulfinimine enantioselective preparation; oxathiazolidine oxide Grignard reagent aldehyde multicomponent reaction.

Two oxathiozolidine-S-oxide templates have been developed and used in a four-component coupling protocol for the synthesis of a wide range of chiral sulfinimines in high enantiomeric excesses. The templates can be synthesized from cheap commodity chems. in three steps in high yields. Furthermore the template is easily recovered in high yields for recycling.

Chemistry – A European Journal published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Reference of 1003-32-3.

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

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

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