Category: 198904-53-9

Richter, Anja; Rose, Rolf; Hedberg, Christian; Waldmann, Herbert; Ottmann, Christian published the artcile< An Optimised Small-Molecule Stabiliser of the 14-3-3-PMA2 Protein-Protein Interaction>, Category: thiazole, the main research area is pyrrolidone derivative stabilizer PMA2 protein interaction crystal structure.

Modulation of protein-protein interactions (PPIs) is a highly demanding, but also a very promising approach in chem. biol. and targeted drug discovery. In contrast to inhibiting PPIs with small, chem. tractable mols., stabilization of these interactions can only be achieved with complex natural products, like rapamycin, FK506, taxol, forskolin, brefeldin and fusicoccin. Fusicoccin stabilizes the activatory complex of the plant H+-ATPase PMA2 and 14-3-3 proteins. Recently, the stabilizing effect of fusicoccin could be mimicked by a trisubstituted pyrrolinone (pyrrolidone1, 1). Here, the authors report the synthesis, functional activity and crystal structure of derivatives of 1 that stabilize the 14-3-3-PMA2 complex. With a limited compound collection three modifications that are important for activity enhancement could be determined: (1) conversion of the pyrrolinone scaffold into a pyrazole, (2) introduction of a tetrazole moiety to the Ph ring that contacts PMA2, and (3) addition of a bromine to the Ph ring that exclusively contacts the 14-3-3 protein. The crystal structure of a pyrazole derivative of 1 in complex with 14-3-3 and PMA2 revealed that the more rigid core of this mol. positions the stabilizer deeper into the rim of the interface, enlarging especially the contact surface to PMA2. Combination of the aforementioned features gave rise to a mol. (I) that displays a threefold increase in stabilizing the 14-3-3-PMA2 complex over 1. Compound I and the other active derivatives show no effect on two other important 14-3-3 protein-protein interactions, i.e., with CRaf and p53. This is the first study that describes the successful optimization of a PPI stabilizer identified by screening.

Chemistry – A European Journal published new progress about 14-3-3 Proteins Role: BSU (Biological Study, Unclassified), PEP (Physical, Engineering or Chemical Process), BIOL (Biological Study), PROC (Process). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Category: thiazole.

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

Chevillard, Florent; Rimmer, Helena; Betti, Cecilia; Pardon, Els; Ballet, Steven; van Hilten, Niek; Steyaert, Jan; Diederich, Wibke E.; Kolb, Peter published the artcile< Binding-Site Compatible Fragment Growing Applied to the Design of β2-Adrenergic Receptor Ligands>, Application of C10H7NOS, the main research area is beta2 adrenergic receptor ligand fragment based drug design phenylamine.

Fragment-based drug discovery is intimately linked to fragment extension approaches that can be accelerated using software for de novo design. Although computers allow for the facile generation of millions of suggestions, synthetic feasibility is however often neglected. In this study the authors computationally extended, chem. synthesized, and exptl. assayed new ligands for the β2-adrenergic receptor (β2AR) by growing fragment-sized ligands. To address the synthetic tractability issue, the authors’ in silico work-flow aims at derivatized products based on robust organic reactions. The study started from the predicted binding modes of five fragments. The authors suggested a total of eight diverse extensions that were easily synthesized, and further assays showed that four products had an improved affinity (up to 40-fold) compared to their resp. initial fragment. The described work-flow, which the authors call “”growing via merging”” and for which the key tools are available online, can improve early fragment-based drug discovery projects, making it a useful creative tool for medicinal chemists during structure-activity relationship (SAR) studies.

Journal of Medicinal Chemistry published new progress about Computer application (PINGUI toolbox web interface). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Application of C10H7NOS.

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

Ai, Wei; Zhang, Jian; Zalloum, Waleed A.; Jia, Ruifang; Cherukupalli, Srinivasulu; Ding, Xiao; Sun, Zhuosen; Sun, Lin; Jiang, Xiangyi; Ma, Xiuli; Li, Zhong; Wang, Defeng; Huang, Bing; Zhan, Peng; Liu, Xinyong published the artcile< Discovery of novel ""Dual-site"" binding oseltamivir derivatives as potent influenza virus neuraminidase inhibitors>, SDS of cas: 198904-53-9, the main research area is oseltamivir derivative preparation influenza virus neuraminidase inhibitor structure activity; 150-cavity; Active site; Influenza virus; Neuraminidase inhibitors; Oseltamivir derivatives.

From our research group, it was noticed that oseltamivir derivatives targeting 150-cavity of neuraminidase enzyme (NA) could significantly increase antiviral activity. Thus, we further enriched the C5-NH2 position of the oseltamivir structure to obtain more potent oseltamivir derivatives In this article, a series of oseltamivir derivatives were synthesized by modifying the C5-NH2 position of oseltamivir. All the compounds were evaluated for in vitro antiviral activity against H5N1 and H5N8. Encouragingly, compounds I and II exhibited prominent activity, which is similar to oseltamivir carboxylate (OSC); and in NAs inhibitory assay, II showed remarkable potency against N1 (H5N1), N2 (H5N2), N6 (H5N6) and N8 (H5N8). In addition, II demonstrated low cytotoxicity and no obvious toxicity at the dose of 1500 mg/kg in mice. Mol. docking studies of I and II provided a plausible rationale for the high potency against group-1 NAs. This work provided new insights to design further neuraminidase inhibitors, which can help to investigate new potent inhibitors for group-1 and group-2 shortly.

European Journal of Medicinal Chemistry published new progress about Cytotoxicity. 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, SDS of cas: 198904-53-9.

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

Zhang, Dong; Gao, Di; Cai, Jinlin; Wu, Xiaoyu; Qin, Hong; Qiao, Kai; Liu, Chengkou; Fang, Zheng; Guo, Kai published the artcile< The ruthenium-catalyzed meta-selective C-H nitration of various azole ring-substituted arenes>, Product Details of C10H7NOS, the main research area is ruthenium catalyst meta selective nitration azole arene green chem.

The efficient ruthenium-catalyzed meta-selective CAr-H nitration of azole ring substituted arenes has been developed. In this work, Ru3(CO)12 was used as the catalyst, AgNO2 as the nitro source, HPcy3+·BF4- as the ligand, pivalic acid as the additive, and DCE as the solvent, and a wide spectrum of arenes bearing thiazole, pyrazolyl or removable oxazoline directing groups were tolerated in this meta-selective CAr-H nitration, affording the nitrated products in moderate to good yields. Moreover, this study reveals a gentler and environmentally friendly way to access meta-nitration arenes compared to the traditional process.

Organic & Biomolecular Chemistry published new progress about Azoles Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Product Details of C10H7NOS.

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

Jin, Ming Yu; Zhou, Yali; Xiao, Dengmengfei; You, Yipeng; Zhen, Qianqian; Tao, Guanyu; Yu, Peiyuan; Xing, Xiangyou published the artcile< Simultaneous Kinetic Resolution and Asymmetric Induction within a Borrowing Hydrogen Cascade Mediated by a Single Catalyst>, COA of Formula: C10H7NOS, the main research area is unsaturated ketone preparation; alkoxy ketone preparation; ketone amino preparation; alc alkoxy preparation enantioselective; amino alc preparation enantioselective; racemic allylic alc borrowing hydrogen cascade ruthenium catalyst; asymmetric induction; borrowing hydrogen cascade; density functional theory; kinetic resolution; π-π interactions.

In a borrowing hydrogen cascade starting from racemic allylic alcs., one of the enantiomers could be kinetically resolved, while the other enantiomer could be purposely converted to various targeted products, including α,β-unsaturated ketones RC(O)C=CCH2R1 [R = Ph, 4-FC6H4, 2-naphthyl, etc.; R1 = (CH2)6, (CH2)7, OTBS], β-functionalized ketones R2C(O)CH2CH2R3 [R2 = 4-MeSC6H4, 4-t-BuC6H4, 4-MeOC6H4, etc.; R3 = OMe, OEt, morpholino, etc.] and γ-functionalized alcs. R4CH(OH)CH2CH2R5 [R4 = 4-ClC6H4, 4-FC6H4, 2-naphthyl, etc.; R5 = OMe, OBn, morpholino, etc.] was reported. By employing a robust Ru-catalyst, both kinetic resolution and asym. induction were achieved with remarkable levels of efficiency and enantioselectivity. D. functional theory (DFT) calculations suggested that corresponding catalyst-substrate π-π interactions were pivotal to realize the observed stereochem. diversity.

Angewandte Chemie, International Edition published new progress about Alcohols, alkoxy Role: SPN (Synthetic Preparation), PREP (Preparation). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, COA of Formula: C10H7NOS.

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

Pardon, Els; Betti, Cecilia; Laeremans, Toon; Chevillard, Florent; Guillemyn, Karel; Kolb, Peter; Ballet, Steven; Steyaert, Jan published the artcile< Nanobody-Enabled Reverse Pharmacology on G-Protein-Coupled Receptors>, Safety of 4-(Thiazol-2-yl)benzaldehyde, the main research area is nanobody beta2 adrenoreceptor fusion G protein coupled receptor agonist; GPCRs; drug discovery; fragment screening; inhibitors; nanobodies.

The conformational complexity of transmembrane signaling of G-protein-coupled receptors (GPCRs) is a central hurdle for the design of screens for receptor agonists. In their basal states, GPCRs have lower affinities for agonists compared to their G-protein-bound active state conformations. Moreover, different agonists can stabilize distinct active receptor conformations and do not uniformly activate all cellular signaling pathways linked to a given receptor (agonist bias). Comparative fragment screens were performed on a β2-adrenoreceptor-nanobody fusion locked in its active-state conformation by a G-protein-mimicking nanobody, and the same receptor in its basal-state conformation. This simple biophys. assay allowed the identification and ranking of multiple novel agonists and permitted classification of the efficacy of each hit in agonist, antagonist, or inverse agonist categories, thereby opening doors to nanobody-enabled reverse pharmacol.

Angewandte Chemie, International Edition published new progress about Chimeric fusion proteins Role: BPN (Biosynthetic Preparation), BUU (Biological Use, Unclassified), PRP (Properties), BIOL (Biological Study), PREP (Preparation), USES (Uses) (β2-adrenoceptors-nanobody). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Safety of 4-(Thiazol-2-yl)benzaldehyde.

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

Jin, Ming Yu; Zhou, Yali; Xiao, Dengmengfei; You, Yipeng; Zhen, Qianqian; Tao, Guanyu; Yu, Peiyuan; Xing, Xiangyou published the artcile< Simultaneous Kinetic Resolution and Asymmetric Induction within a Borrowing Hydrogen Cascade Mediated by a Single Catalyst>, Category: thiazole, the main research area is unsaturated ketone preparation; alkoxy ketone preparation; ketone amino preparation; alc alkoxy preparation enantioselective; amino alc preparation enantioselective; racemic allylic alc borrowing hydrogen cascade ruthenium catalyst; asymmetric induction; borrowing hydrogen cascade; density functional theory; kinetic resolution; π-π interactions.

In a borrowing hydrogen cascade starting from racemic allylic alcs., one of the enantiomers could be kinetically resolved, while the other enantiomer could be purposely converted to various targeted products, including α,β-unsaturated ketones RC(O)C=CCH2R1 [R = Ph, 4-FC6H4, 2-naphthyl, etc.; R1 = (CH2)6, (CH2)7, OTBS], β-functionalized ketones R2C(O)CH2CH2R3 [R2 = 4-MeSC6H4, 4-t-BuC6H4, 4-MeOC6H4, etc.; R3 = OMe, OEt, morpholino, etc.] and γ-functionalized alcs. R4CH(OH)CH2CH2R5 [R4 = 4-ClC6H4, 4-FC6H4, 2-naphthyl, etc.; R5 = OMe, OBn, morpholino, etc.] was reported. By employing a robust Ru-catalyst, both kinetic resolution and asym. induction were achieved with remarkable levels of efficiency and enantioselectivity. D. functional theory (DFT) calculations suggested that corresponding catalyst-substrate π-π interactions were pivotal to realize the observed stereochem. diversity.

Angewandte Chemie, International Edition published new progress about Alcohols, alkoxy Role: SPN (Synthetic Preparation), PREP (Preparation). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Category: thiazole.

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

Pardon, Els; Betti, Cecilia; Laeremans, Toon; Chevillard, Florent; Guillemyn, Karel; Kolb, Peter; Ballet, Steven; Steyaert, Jan published the artcile< Nanobody-Enabled Reverse Pharmacology on G-Protein-Coupled Receptors>, Recommanded Product: 4-(Thiazol-2-yl)benzaldehyde, the main research area is nanobody beta2 adrenoreceptor fusion G protein coupled receptor agonist; GPCRs; drug discovery; fragment screening; inhibitors; nanobodies.

The conformational complexity of transmembrane signaling of G-protein-coupled receptors (GPCRs) is a central hurdle for the design of screens for receptor agonists. In their basal states, GPCRs have lower affinities for agonists compared to their G-protein-bound active state conformations. Moreover, different agonists can stabilize distinct active receptor conformations and do not uniformly activate all cellular signaling pathways linked to a given receptor (agonist bias). Comparative fragment screens were performed on a β2-adrenoreceptor-nanobody fusion locked in its active-state conformation by a G-protein-mimicking nanobody, and the same receptor in its basal-state conformation. This simple biophys. assay allowed the identification and ranking of multiple novel agonists and permitted classification of the efficacy of each hit in agonist, antagonist, or inverse agonist categories, thereby opening doors to nanobody-enabled reverse pharmacol.

Angewandte Chemie, International Edition published new progress about Chimeric fusion proteins Role: BPN (Biosynthetic Preparation), BUU (Biological Use, Unclassified), PRP (Properties), BIOL (Biological Study), PREP (Preparation), USES (Uses) (β2-adrenoceptors-nanobody). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Recommanded Product: 4-(Thiazol-2-yl)benzaldehyde.

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

Richter, Anja; Rose, Rolf; Hedberg, Christian; Waldmann, Herbert; Ottmann, Christian published the artcile< An Optimised Small-Molecule Stabiliser of the 14-3-3-PMA2 Protein-Protein Interaction>, Formula: C10H7NOS, the main research area is pyrrolidone derivative stabilizer PMA2 protein interaction crystal structure.

Modulation of protein-protein interactions (PPIs) is a highly demanding, but also a very promising approach in chem. biol. and targeted drug discovery. In contrast to inhibiting PPIs with small, chem. tractable mols., stabilization of these interactions can only be achieved with complex natural products, like rapamycin, FK506, taxol, forskolin, brefeldin and fusicoccin. Fusicoccin stabilizes the activatory complex of the plant H+-ATPase PMA2 and 14-3-3 proteins. Recently, the stabilizing effect of fusicoccin could be mimicked by a trisubstituted pyrrolinone (pyrrolidone1, 1). Here, the authors report the synthesis, functional activity and crystal structure of derivatives of 1 that stabilize the 14-3-3-PMA2 complex. With a limited compound collection three modifications that are important for activity enhancement could be determined: (1) conversion of the pyrrolinone scaffold into a pyrazole, (2) introduction of a tetrazole moiety to the Ph ring that contacts PMA2, and (3) addition of a bromine to the Ph ring that exclusively contacts the 14-3-3 protein. The crystal structure of a pyrazole derivative of 1 in complex with 14-3-3 and PMA2 revealed that the more rigid core of this mol. positions the stabilizer deeper into the rim of the interface, enlarging especially the contact surface to PMA2. Combination of the aforementioned features gave rise to a mol. (I) that displays a threefold increase in stabilizing the 14-3-3-PMA2 complex over 1. Compound I and the other active derivatives show no effect on two other important 14-3-3 protein-protein interactions, i.e., with CRaf and p53. This is the first study that describes the successful optimization of a PPI stabilizer identified by screening.

Chemistry – A European Journalpublished new progress about 14-3-3 Proteins Role: BSU (Biological Study, Unclassified), PEP (Physical, Engineering or Chemical Process), BIOL (Biological Study), PROC (Process). 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Formula: C10H7NOS.

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

Bold, Guido; Faessler, Alexander; Capraro, Hans-Georg; Cozens, Robert; Klimkait, Thomas; Lazdins, Janis; Mestan, Juergen; Poncioni, Bernard; Roesel, Johannes; Stover, David; Tintelnot-Blomley, Marina; Acemoglu, Figan; Beck, Werner; Boss, Eugen; Eschbach, Martin; Huerlimann, Thomas; Masso, Elvira; Roussel, Serge; Ucci-Stoll, Katharina; Wyss, Dominique; Lang, Marc published the artcile< New Aza-Dipeptide Analogs as Potent and Orally Absorbed HIV-1 Protease Inhibitors: Candidates for Clinical Development>, Reference of 198904-53-9, the main research area is human immunodeficiency virus protease inhibitor azapeptide; azadipeptide analog preparation HIV protease inhibitor; azapeptide analog preparation antiviral.

On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex, aza-dipeptide analogs, e.g. I (R1 = Ph, pyrid-2-yl, thiazol-2-yl, thiazol-5-yl, diethylamino, 2-methyl-2H-tetrazol-5-yl, 2-tert-butyl-2H-tetrazole-5-yl; R2, R3 = iso-Pr, sec-Bu, tert-Bu; R4 = MeO, EtO) carrying N-(bis-aryl-methyl) substituents on the (hydroxyethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally or orthogonally protected dipeptide isosteres, sym. and asym. acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxyethyl)hydrazine dipeptide isostere with N-(methoxycarbonyl)-L-tert-leucine increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives The bis(L-tert-leucine) derivatives I (R1 = Ph (CGP 75355), pyrid-2-yl (CGP 73547), thiazol-2-yl (CGP 75136), 2-methyl-2H-tetrazol-5-yl (CGP 75176); R2 = R3 = tert-butyl; R4 = OMe) combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clin. candidates.

Journal of Medicinal Chemistrypublished new progress about Antiviral agents. 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Reference of 198904-53-9.

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