Day: November 10, 2022

Huang, David S. published the artcileSynthesis and Cytotoxicity Evaluation of C4- and C5-Modified Analogues of the α,β-Unsaturated Lactone of Pironetin, Computed Properties of 171877-39-7, the main research area is pironetin analog preparation antitumor structure activity; antitumor agents; natural products; tubulin binding agents; α,β-unsaturated lactones; α-tubulin.

Pironetin is a natural product with potent antiproliferative activity that forms a covalent adduct with α-tubulin via conjugate addition into the natural product’s α,β-unsaturated lactone. Although pironetin’s α,β-unsaturated lactone is involved in its binding to tubulin, the structure-activity relationship at different positions of the lactone have not been thoroughly evaluated. For a systematic evaluation of the structure-activity relationships at the C4 and C5 positions of the α,β-unsaturated lactone of pironetin, twelve analogs of the natural product, I (R1 = R2 = H, Me; R1 = Me, n-Pr, CH2CF3, cyclopropyl, iso-Bu, CH2Ph, iso-Pr, R2 = H; R1 = H, R1 = Et) and II (R1 = Et, R2 = H; R1 = H, R2 = Et), were prepared by total synthesis. Modifying the stereochem. at the C4 and/or C5 positions of the α,β-unsaturated lactone of pironetin resulted in loss of antiproliferative activity in OVCAR5 ovarian cancer cells. While changing the C4 Et substituent with groups such as Me, Pr, cyclopropyl, and iso-Bu were tolerated, groups with larger steric properties such as an iso-Pr and benzyl groups were not.

ChemMedChem published new progress about Antitumor agents. 171877-39-7 belongs to class thiazole, name is (S)-4-Benzylthiazolidine-2-thione, and the molecular formula is C10H11NS2, Computed Properties of 171877-39-7.

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

Kozikowski, Alan P. published the artcileChemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth, Name: 4-(2-Nitrophenyl)thiazole-2-amine, the main research area is histone deacetylase inhibitor biaryl hydroxamate mercaptoacetamide preparation QSAR; pancreatic cancer inhibitor biaryl hydroxamate mercaptoacetamide preparation QSA.

The histone deacetylases (HDACs) are able to regulate gene expression, and inhibitors of the HDACs (HDACIs) hold promise in the treatment of cancer as well as a variety of neurodegenerative diseases. To investigate the potential for isoform selectivity in the inhibition of HDACs, we prepared a small series of 2,4′-diaminobiphenyl ligands functionalized at the para-amino group with an appendage containing either a hydroxamate or a mercaptoacetamide group and coupled to an amino acid residue at the ortho-amino group. A smaller series of substituted phenylthiazoles was also explored. Some of these newly synthesized ligands show low-nanomolar potency in HDAC inhibition assays and display micromolar to low-nanomolar IC50 values in tests against five pancreatic cancer cell lines. The isoform selectivity of these ligands for class I HDACs (HDAC1-3 and 8) and class IIb HDACs (HDAC6 and 10) together with QSAR studies of their correlation with lipophilicity are presented. Of particular interest is the selectivity of the mercaptoacetamides for HDAC6.

ChemMedChem published new progress about Antitumor agents. 90323-06-1 belongs to class thiazole, name is 4-(2-Nitrophenyl)thiazole-2-amine, and the molecular formula is C9H7N3O2S, Name: 4-(2-Nitrophenyl)thiazole-2-amine.

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

Zhang, Qian published the artcileDiscovery of Triazolo-pyridazine/-pyrimidine Derivatives Bearing Aromatic (Heterocycle)-Coupled Azole Units as Class II c-Met Inhibitors, Application In Synthesis of 144060-99-1, the main research area is triazolopyridazine triazolopyrimidine preparation cMet kinase inhibition SAR anticancer human.

Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, synthesized, and evaluated for their inhibitory activity against c-Met kinase, as well as three c-Met overexpressed cancer cell lines (A549, MCF-7, and HeLa) and one normal human hepatocytes cell line LO2 in vitro. The most promising compound I exhibited significant cytotoxicity against A549, MCF-7, and HeLa cell lines with IC50 values of 1.06 +/- 0.16, 1.23 +/- 0.18, and 2.73 +/- 0.33μM, resp. Moreover, the inhibitory activity of compound I against c-Met kinase (IC50 = 0.090μM) was equal to that of Foretinib (IC50 = 0.019μM). The result of the acridine orange single staining test demonstrated that compound I could remarkably induce apoptosis of A549 cells. The results of apoptosis and cycle distribution of cells showed that compound I could induce late apoptosis of A549 cells and stimulate A549 cells arresting in the G0/G1 phase. Structure-activity relationships (SARs), pharmacol. results, and docking studies indicated that the introduction of 5-methylthiazole fragment to the five-atom moiety was beneficial for the activity. So far, the existing data indicated that I may become a potential class II c-Met inhibitor.

ACS Omega published new progress about Antitumor agents. 144060-99-1 belongs to class thiazole, name is 2-(4-Fluorophenyl)-4-methylthiazole-5-carboxylic acid, and the molecular formula is C11H8FNO2S, Application In Synthesis of 144060-99-1.

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

Marson, Charles M. published the artcileDiscovery of Potent, Isoform-Selective Inhibitors of Histone Deacetylase Containing Chiral Heterocyclic Capping Groups and a N-(2-Aminophenyl)benzamide Binding Unit, Recommanded Product: (S)-4-Benzylthiazolidine-2-thione, the main research area is aminophenylbenzamide pyrimidine imidazolinone thiazoline capped preparation histone deacetylase inhibition; thiazoline capped HDAC3 NCoR1 inhibitor preparation antitumor activity apoptosis.

The synthesis of a novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contain a heterocyclic capping group and a N-(2-aminophenyl)benzamide unit that binds in the active site. In vitro assays for the inhibition of HDAC1, HDAC2, HDAC3-NCoR1, and HDAC8 by the N-(2-aminophenyl)benzamide I gave resp. IC50 values of 930, 85, 12, and 4100 nM, exhibiting class I selectivity and potent inhibition of HDAC3-NCoR1. Both imidazolinone and thiazoline rings are shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)benzamides previously reported, an example of each ring system at 1 μM causing an increase in histone H3K9 acetylation in the human cell lines Jurkat and HeLa and an increase in cell death consistent with induction of apoptosis. Inhibition of the growth of MCF-7, A549, DU145, and HCT116 cell lines by I was observed, with resp. IC50 values of 5.4, 5.8, 6.4, and 2.2 mM.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 171877-39-7 belongs to class thiazole, name is (S)-4-Benzylthiazolidine-2-thione, and the molecular formula is C10H11NS2, Recommanded Product: (S)-4-Benzylthiazolidine-2-thione.

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

De, Surya K. published the artcileDesign, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase, Product Details of C11H9NO2S, the main research area is preparation structure thiophene carboxamide derivative dual inhibitor JNK kinase; thiophene carboxamide derivative dual ATP JIP inhibitor JNK kinase.

We report comprehensive structure-activity relationship studies on a novel series of c-Jun N-terminal kinase (JNK) inhibitors. Intriguingly, the compounds have a dual inhibitory activity by functioning as both ATP and JIP mimetics, possibly by binding to both the ATP binding site and to the docking site of the kinase. Several of such novel compounds display potent JNK inhibitory profiles both in vitro and in cell.

Bioorganic & Medicinal Chemistry published new progress about Enzyme inhibitors. 16441-28-4 belongs to class thiazole, name is 2-(2-Phenylthiazol-4-yl)acetic acid, and the molecular formula is C11H9NO2S, Product Details of C11H9NO2S.

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

Weinstock, Joseph published the artcileSynthesis and evaluation of non-catechol D-1 and D-2 dopamine receptor agonists: benzimidazol-2-one, benzoxazol-2-one, and the highly potent: benzothiazol-2-one 7-ethylamines, HPLC of Formula: 108773-00-8, the main research area is benzimidazolone ethylamine preparation dopaminergic; benzoxazolone ethylamine preparation dopaminergic; benzothiazolone ethylamine preparation dopaminergic; dopaminergic benzimidazolone benzoxazolone benzothiazolone; dopamine receptor agonist non catechol.

Title heterocyclic compounds I, II, and III (R = R1 = Pr, R2 = H, Cl, R3 = OH; R = R1 = Pr, H, R2 = R3 = H; R = R2 = H, R1 = H, Me, R3 = OH) were prepared by standard methods. Thus, III (R = R1 = Pr, R2 = Cl, R3 = OH) was prepared from phenylacetic acid IV in several steps in which the key step was the cyclization of aminobenzenethiol V with COCl2 to give III (R = R1 = Pr, R2 = Cl, R3 = OMe). These compounds were evaluated for their affinity and agonist activity at D-1 and D-2 receptors by using in vitro assays. Replacement of the m-hydroxyl in N,N-dipropyldopamine with the thiazol-2-one group resulted in a dramatic increase in D-2 receptor affinity and activity compared to that of N,N-dipropyldopamine or to that of oxindole VI. III (R = R1 = Pr, R2 = H, R3 = OH) is the most potent D-2 receptor agonist reported to date in the field-stimulated rabbit ear artery (ED50 = 0.028 nM). I and II showed D-2 receptor agonist potency similar to that of VI.

Journal of Medicinal Chemistry published new progress about Dopamine agonists. 108773-00-8 belongs to class thiazole, name is 2-Chloro-4-methoxy-7-methylbenzo[d]thiazole, and the molecular formula is C9H8ClNOS, HPLC of Formula: 108773-00-8.

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

Shi, Min published the artcileSynthesis of a novel copper(II) complex and its crystal structure, COA of Formula: C10H11NS2, the main research area is copper thiazolidinethione complex preparation structure; crystal structure copper thiazolidinethione complex.

One novel chiral Cu(II) complex was successfully synthesized from the reaction of chiral 1,3-thiazolidine-2-thione ligand with CuCl2 in CH2Cl2 in the presence of Et3N and DMAP at room temperature Its unique crystal structure was unambiguously disclosed by x-ray anal. The crystal is tetragonal, space group I4(1), a 15.0875(11), b 15.0875(11), c 19.362(3) Å, V = 4407.4(8) A3, Z = 8, ρcalc = 1.639 mg cm-3.

Journal of Organometallic Chemistry published new progress about Crystal structure. 171877-39-7 belongs to class thiazole, name is (S)-4-Benzylthiazolidine-2-thione, and the molecular formula is C10H11NS2, COA of Formula: C10H11NS2.

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

Shi, Min published the artcileSynthesis of novel chiral Cu or Ag/S,N cluster complexes and absolute stereostructures as determined by X-ray crystallography, Name: (S)-4-Benzylthiazolidine-2-thione, the main research area is copper silver chiral thiazolidinethione ligand complex preparation structure; crystal structure copper silver chiral thiazolidinethione ligand complex.

Novel chiral Cu(I) and Ag(I) metal complexes were synthesized from the reaction of chiral (S)-(-)-4-benzyl-1,3-thiazolidine-2-thione ligand with CuCl and AgOAc in CH2Cl2 in the presence of Et3N and DMAP at room temperature Their unique crystal structures were determined by x-ray anal. Four Cu(I) atoms and four 1,3-thiazolidine-2-thione ligands form a butterfly-type metal cluster. Six Ag(I) atoms and six 1,3-thiazolidine-2-thione ligands form another butterfly-type cluster.

Chirality published new progress about Crystal structure. 171877-39-7 belongs to class thiazole, name is (S)-4-Benzylthiazolidine-2-thione, and the molecular formula is C10H11NS2, Name: (S)-4-Benzylthiazolidine-2-thione.

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

Feng, Xixi published the artcileStructure-Affinity Relationship Analysis of Selective FKBP51 Ligands, Recommanded Product: (S)-4-Benzylthiazolidine-2-thione, the main research area is crystal structure FKBP protein psychiatric metabolic disorder.

The FK506-binding protein 51 (FKBP51) is a promising drug target for the treatment of stress-related psychiatric or metabolic disorders. Just recently, the first selective ligands for FKBP51 were reported based on an induced fit mechanism, but they are too large for a further drug development process. The authors therefore designed and synthesized a novel series of selective ligands to explore the requirements necessary for binding to the induced-fit conformation. All ligands of this series show no binding toward the structurally very similar antitarget FKBP52. With the cocrystal structure of the best ligand in this novel series the authors confirmed the induced fit mechanism. Furthermore, the structure-affinity relationship provides information about beneficial structural features, which is valuable for the development of improved FKBP51-directed drugs.

Journal of Medicinal Chemistry published new progress about Crystal structure. 171877-39-7 belongs to class thiazole, name is (S)-4-Benzylthiazolidine-2-thione, and the molecular formula is C10H11NS2, Recommanded Product: (S)-4-Benzylthiazolidine-2-thione.

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

Yan, Gang published the artcile2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies, Product Details of C9H7N3O2S, the main research area is thiazolyl imidazolyl acetamide preparation mol docking BACE1 inhibitor human; Alzheimer’s disease; BACE-1 inhibitors; BBB; Docking study; PAMPA; Permeability; Surface Plasmon Resonance (SPR).

In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives, I (R1 = Ph, 4-MeC6H4, 2-O2NC6H4, etc.; R2 = 2-MeOC6H4,3-MeOC6H4, 4-MeOC6H4, 3-EtOC6H4), II (R3 = Ph, 3,5-Cl2-4-NH2Ph; R4 = 3-MeOPh, 3-EtOPh), were developed as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biol. evaluated in vitro. In addition, the selected compounds were tested with affinity (KD) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog II (R3 = Ph; R4 = 3-EtOC6H4) (IC50 = 4.6 μM) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization.

European Journal of Medicinal Chemistry published new progress about Alzheimer disease. 90323-06-1 belongs to class thiazole, name is 4-(2-Nitrophenyl)thiazole-2-amine, and the molecular formula is C9H7N3O2S, Product Details of C9H7N3O2S.

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