Category: 1003-32-3

Fushimi, Makoto; Buck, Hannes; Balbach, Melanie; Gorovyy, Anna; Ferreira, Jacob; Rossetti, Thomas; Kaur, Navpreet; Levin, Lonny R.; Buck, Jochen; Quast, Jonathan; van den Heuvel, Joop; Steegborn, Clemens; Finkin-Groner, Efrat; Kargman, Stacia; Michino, Mayako; Foley, Michael A.; Miller, Michael; Liverton, Nigel J.; Huggins, David J.; Meinke, Peter T. published the artcile< Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10)>, Computed Properties of 1003-32-3, the main research area is adenylyl cyclase inhibitor oral bioavailability.

Soluble adenylyl cyclase (sAC) has gained attention as a potential therapeutic target given the role of this enzyme in intracellular signaling. We describe successful efforts to design improved sAC inhibitors amenable for in vivo interrogation of sAC inhibition to assess its potential therapeutic applications. This work culminated in the identification of TDI-10229 (12), which displays nanomolar inhibition of sAC in both biochem. and cellular assays and exhibits mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound

ACS Medicinal Chemistry Letters published new progress about Drug design. 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

Kim, Ho Shin; Hammill, Jared T.; Scott, Daniel C.; Chen, Yizhe; Rice, Amy L.; Pistel, William; Singh, Bhuvanesh; Schulman, Brenda A.; Guy, R. Kiplin published the artcile< Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M>, Formula: C4H3NOS, the main research area is carcinoma DCN1 UBE2M interaction inhibitors NEDD8 pharmacokinetic oral bioavailability.

The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40 (I), inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochem. assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Addnl., we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochem. IC90 for 24 h in mice.

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

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

Kang, Taeho; Erbay, Tugce G.; Xu, Kane L.; Gallego, Gary M.; Burtea, Alexander; Nair, Sajiv K.; Patman, Ryan L.; Zhou, Ru; Sutton, Scott C.; McAlpine, Indrawan J.; Liu, Peng; Engle, Keary M. published the artcile< Multifaceted Substrate-Ligand Interactions Promote the Copper-Catalyzed Hydroboration of Benzylidenecyclobutanes and Related Compounds>, Category: thiazole, the main research area is copper catalyzed hydroboration benzylidenecyclobutane diborane kinetics; chloro copper bisphosphinobenzene complex preparation crystal structure; mol structure chloro copper bisphosphinobenzene complex; 4-membered rings; Copper catalysis; benzylidenecyclobutanes; heterocycle; hydroborations; modified dppbz ligands; tertiary boronic esters.

A unified synthetic strategy to access tertiary four-membered carbo/heterocyclic boronic esters is reported. The use of a Cu(I) catalyst in combination with a modified 1,2-bis(diphenylphosphino)benzene (dppbz) ligand enables regioselective hydroboration of various trisubstituted benzylidenecyclobutanes and carbo/heterocyclic analogs. The reaction conditions are mild, and the method tolerates a wide range of medicinally relevant heteroarenes. The protocol can be conveniently conducted on a gram scale, and the tertiary boronic ester products undergo facile diversification into valuable targets. Reaction kinetics and computational studies indicate that the migratory insertion step is turnover-limiting and accelerated by electron-withdrawing groups on the dppbz ligand. Energy decomposition anal. calculations reveal that electron-deficient P-aryl groups on the dppbz ligand enhance the T-shaped π/π interactions with the substrate and stabilize the migratory insertion transition state.

ACS Catalysis published new progress about Aromatic hydrocarbons Role: SPN (Synthetic Preparation), PREP (Preparation) (benzylcyclobutane heteroarenes). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Category: thiazole.

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

Gwaltney, Stephen L.; O’Connor, Stephen J.; Nelson, Lissa T. J.; Sullivan, Gerard M.; Imade, Hovis; Wang, Weibo; Hasvold, Lisa; Li, Qun; Cohen, Jerome; Gu, Wen-Zhen; Tahir, Stephen K.; Bauch, Joy; Marsh, Kennan; Ng, Shi-Chung; Frost, David J.; Zhang, Haiying; Muchmore, Steve; Jakob, Clarissa G.; Stoll, Vincent; Hutchins, Charles; Rosenberg, Saul H.; Sham, Hing L. published the artcile< Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives>, Quality Control of 1003-32-3, the main research area is glycine phenylalanine histidine derivative synthesis antitumor agent farnesyltransferase inhibitor; aryl tetrahydropyridine inhibitor farnesyltransferase antitumor structure activity; antitumor agent histidine methionine derivative crystal structure.

Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clin. trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. The design, synthesis, SAR and biol. properties of these compounds will be discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about Amino acids Role: BSU (Biological Study, Unclassified), PAC (Pharmacological Activity), PKT (Pharmacokinetics), PRP (Properties), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 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

Zhong, Zhao-Jin; Zhang, Da-Jun; Peng, Zong-Gen; Li, Yu-Huan; Shan, Guang-Zhi; Zuo, Li-Min; Wu, Lin-Tao; Li, Si-Yang; Gao, Rong-Mei; Li, Zhuo-Rong published the artcile< Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines>, Name: Thiazole-5-carboxyaldehyde, the main research area is preparation oxazole antiviral human treatment viral infection HCV; (5-Oxazolyl)phenyl amine; Antiviral activity; Structure–activity relationships; Synthesis.

A series of novel (5-oxazolyl)phenyl amine derivatives were synthesized and their antiviral activities against the hepatitis C virus (HCV) and the coxsackie virus B3 (CVB3) and B6 (CVB6) were evaluated in vitro. Bioassays showed that the synthesized compounds 17a1, 17a4, 17a6, 17b1, 17d1, 17e2 and 17g3 exhibited potent antiviral activity against HCV (IC50 = 0.28-0.92 μM) and most synthesized compounds exhibited low cytotoxicity in Huh7.5 cells, compared to telaprevir. The compounds 17a1, 17a4, 17a5, 17a6, 17b1, 17b2, 17g1 and 17g3 showed strong activity against the CVB3 and/or CVB6 at low concentrations (IC50 < 2.0 μM). The (5-oxazolyl)phenyl amines 17a1, 17a4, 17a8, 17b1, 17d1, 17e2, 17f3 and 17g3 were identified as the most active on the biol. assays, and will be studied further. European Journal of Medicinal Chemistry published new progress about Antiviral agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Name: Thiazole-5-carboxyaldehyde.

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

Sieng, Bora; Maldonado, Matias Funes; Romagnoli, Carlo; Amedjkouh, Mohamed published the artcile< One-Pot Alkynylation of Azaaryl Aldehydes and Spontaneous Base-Free Rearrangement into Enone Esters: an Autoinductive Mechanism>, Formula: C4H3NOS, the main research area is unsaturated ketoester diastereoselective preparation; butyllithium methylzinc catalyst addition propiolate heteroaryl aldehyde stereoselective rearrangement; isotope labeling allenoate trapping mechanism addition rearrangement propargylic alc.

When heteroaromatic aldehydes are reacted with Et propiolate in the presence of Me2Zn or BuLi, γ-oxo-α,β-unsaturated esters were generated by spontaneous rearrangements of the intermediate propargylic alcs.; in some cases, the propargyl alcs. were formed without rearrangement. The mechanism of the rearrangement was studied using isotope labeling and trapping of a proposed allenoate intermediate; an autocatalytic mechanism is proposed.

European Journal of Organic Chemistry published new progress about Addition reaction. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Formula: C4H3NOS.

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

Yu, Ming; Lizarzaburu, Mike; Motani, Alykhan; Fu, Zice; Du, Xiaohui; Liu, Jiwen; Jiao, Xianyun; Lai, SuJen; Fan, Peter; Fu, Angela; Liu, Qingxiang; Murakoshi, Michiko; Nara, Futoshi; Oda, Kozo; Okuyama, Ryo; Reagan, Jeff D.; Watanabe, Nobuaki; Yamazaki, Mami; Xiong, Yumei; Zhang, Ying; Zhuang, Run; Lin, Daniel C.-H.; Houze, Jonathan B.; Medina, Julio C.; Li, Leping published the artcile< Aminopyrazole-Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies>, SDS of cas: 1003-32-3, the main research area is amrinone phenylalanine carboxylic acid preparation GPR142 agonist structure design; pharmacokinetics bioavailability diabetes amrinone phenylalanine carboxylic acid antidiabetic prodrug; glucose tolerance insulin secretagogue human islet transplant CYP450 hERG; GPR142 agonist; aminopyrazole−phenylalanine; human islet transplant; insulin secretagogue; oral glucose tolerance test; prodrug; type 2 diabetes.

Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid I, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P 450 or hERG liability. Compound I, together with its orally bioavailable Et ester prodrug II, were found to be suitable for in vivo proof-of-concept studies. Compound II displayed good efficacy in a mouse oral glucose tolerance test (OGTT). CompoundI showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

ACS Medicinal Chemistry Letters published new progress about Antidiabetic agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, SDS of cas: 1003-32-3.

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

Sun, Wencheng; Teng, Qiaoling; Cheng, Dongping; Li, Xiaonian; Xu, Xiaoliang published the artcile< The hydrodebromination of 1,1-dibromoalkenes via visible light catalysis>, Computed Properties of 1003-32-3, the main research area is dibromoalkene preparation iridium photocatalyst diastereoselective hydrodebromination green chem; bromoalkene preparation.

A hydrodebromination reaction of 1,1-dibromoalkenes was established via visible light catalysis. A variety of structurally different vinyl bromides were obtained in moderate to excellent yields.

Tetrahedron Letters 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, Computed Properties of 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>, Application In Synthesis of 1003-32-3, 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 Chemistry 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, Application In Synthesis of 1003-32-3.

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

Kerdesky, Francis A. J.; Seif, Louis S. published the artcile< Catalytic hydrogenation of halothiazoles>, Related Products of 1003-32-3, the main research area is halothiazole hydrogenation dechlorination palladium catalyst.

The hydrogenation of halothiazoles I (R = R1 = H, R2 = Br; R = R1 = Br, R2 = H; R = R2 = Br, Cl, R1 = CHO, CH2OH) to I (R = R2 = H, R1 = H, CHO, CH2OH) is described. The best results were obtained utilizing 10% palladium on carbon as catalyst at four atmospheres of pressure with the bromide derivatives

Synthetic Communications published new progress about Dechlorination. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Related Products of 1003-32-3.

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