Category: 31166-29-7

Kato, Yusuke; Hin, Niyada; Maita, Nobuo; Thomas, Ajit G.; Kurosawa, Sumire; Rojas, Camilo; Yorita, Kazuko; Slusher, Barbara S.; Fukui, Kiyoshi; Tsukamoto, Takashi published the artcile< Structural basis for potent inhibition of D-amino acid oxidase by thiophene carboxylic acids>, Category: chlorides-buliding-blocks, the main research area is thiophene carboxylate inhibitor amino acid oxidase DAO crystal structure; Drug discovery; Flavoenzyme; Molecular dynamics; Schizophrenia; X-ray crystallography.

A series of thiophene-2-carboxylic acids and thiophene-3-carboxylic acids were identified as a new class of DAO inhibitors. Structure-activity relationship (SAR) studies revealed that small substituents are well-tolerated on the thiophene ring of both the 2-carboxylic acid and 3-carboxylic acid scaffolds. Crystal structures of human DAO in complex with potent thiophene carboxylic acids revealed that Tyr224 was tightly stacked with the thiophene ring of the inhibitors, resulting in the disappearance of the secondary pocket observed with other DAO inhibitors. Mol. dynamics simulations of the complex revealed that Tyr224 preferred the stacked conformation irresp. of whether Tyr224 was stacked or not in the initial state of the simulations. MM/GBSA indicated a substantial hydrophobic interaction between Tyr244 and the thiophene-based inhibitor. In addition, the active site was tightly closed with an extensive network of hydrogen bonds including those from Tyr224 in the stacked conformation. The introduction of a large branched side chain to the thiophene ring markedly decreased potency. These results are in marked contrast to other DAO inhibitors that can gain potency with a branched side chain extending to the secondary pocket due to Tyr224 repositioning. These insights should be of particular importance in future efforts to optimize DAO inhibitors with novel scaffolds.

European Journal of Medicinal Chemistry published new progress about Conformational transition. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Profft, Elmar; John, Peter published the artcile< Studies on thiophene. XII>, Recommanded Product: 4,5-Dichlorothiophene-2-carboxylic acid, the main research area is .

The transformation of 2,3-dichloro-5-(chloromethyl)thiophene (I) to 2,3-dichlorothiophene-5-acetonitrile (II) and 2,3-dichlorothiophene-5-acetic acid (III) was studied. As II was not formed from I + KCN in Me2CO, the reaction was carried out in EtOH-H2O. In 1 hr. 67 g. I was added to a boiling solution of 31 g. KCN in 50 cc. H2O and 20 cc. EtOH, and the mixture boiled for 5 hrs. and cooled, and 200 cc. H2O was added. The aqueous phase was separated and extracted twice with Et2O, which was combined with the oily product, dried over Na2SO4, and distilled at 99-104°/1 mm. Washing with cold petr. ether yielded 10.2 g. II, yellow prisms, m. 45°. Saponification of I was best done by acidic hydrolysis in MeOH. A slow current of dry HCl was led through 10 g. II in 30 cc. MeOH. A solid intermediate was formed. After saturation with HCl, 30 cc. H2O was added, whereupon the mixture was kept 3 days. A yellowish oil separated (III Me ester), b16 124-8°, from which III was obtained with 20% aqueous KOH and purified from NaHCO3 solution to give 1.5 g., m. 106° (petr. ether). Hydrogenation of 5 g. II with 1.3 g. LiAlH4 in 20 cc. Et2O yielded 2,3-dichloro-5-(2-aminoethyl)thiophene. As this compound was unstable, it was isolated as 1.8 g. benzoyl derivative, m. 120°. The high reactivity of I was shown by adding 44 g. I to 5 g. Na and 64 g. CH2(CO2Et)2 in 150 cc. EtOH. The Et ester of bis(2,3-dichlorothienyl)malonic acid (IV) (42 g.), m. 121°, was obtained. Even when smaller amounts of CH2(CO2Et)2 were used, no monosubstituted ester was obtained. Saponification of the Et ester yielded the acid (IV), C13H8Cl4O4S2, m. 171°, which was characterized as the dichloride, m. 137°, diamide m. 285°, di(ethylamide), m. 232° and di(butylamide), m. 221°. At 180° IV decarboxylated, to give 82% β,β’-bis(2,3-dichlorothienyl)isobutyric acid, m. 117°, which was characterized by the amide, m. 144°, butylamide, m. 128°, anilide, m. 199° and 2-naphthylamide, m. 183°. I (2 g.) was kept 6 days with 1.05 g. diethanolamine in 15 cc. Et2O. H2O was added and the acidified solution extracted with Et2O, made alk., and extracted again. The Et2O solution was dried with Na2SO4 and 0.8 g. N-(2,3-dichlorothenyl)diethanolamine-HCl precipitated with dry HCl, m. 138°. From the residue N,O-bis(2,3-dichlorothienyl)diethanolamine-HCl was isolated, m. 163°. In the same way N,N-bis(2,3-dichlorothenyl)ethanolamine-HCl, m. 202°, was obtained from 2 g. I and 1 g. ethanolamine in 15 cc. Et2O; in this reaction no O-substituted compounds could be isolated. 2,3-Dichloro-5-thiophenealdehyde was transformed by a Cannizzaro reaction into the alcohol and 2,3-dichlorothiophenecarboxylic acid (V). V was characterized by its amide, m. 165°, butylamide, m. 83°, ethanolamide, m. 153°, anilide m. 181°, 2-naphthylamide, m. 191° as well as the Me ester, m. 60°.

Journal fuer Praktische Chemie (Leipzig) published new progress about 31166-29-7. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Recommanded Product: 4,5-Dichlorothiophene-2-carboxylic acid.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Stanetty, Peter; Puschautz, Erhard published the artcile< Herbicidal thienylureas. II>, Reference of 31166-29-7, the main research area is thienylurea; thiophenecarboxylic acid preparation Curtius degradation; urea thienyl.

Syntheses of thiophenecarboxylic acids, e.g., I (R = Cl, R1 = Me, MeO; R = Me, R1 = Cl; R = H, R1 = 4-ClC6H4O; R = Me2CH, R1 = H) are described. A modified Curtius degradation was the key step for the formation of thienylureas from I. These thienylureas are related to 2nd generation urea herbicides.

Monatshefte fuer Chemie published new progress about 31166-29-7. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Reference of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Zhu, Linglong; Hu, Haiwen; Qi, Liang; Zheng, Yi; Zhong, Weihui published the artcile< Enantioselective Allylic Substitution of Morita-Baylis-Hillman Adducts Catalyzed by Chiral Bifunctional Ferrocenylphosphines>, Application In Synthesis of 31166-29-7, the main research area is enantioselective allylic substitution Morita Baylis Hillman adduct ferrocenylphosphine catalyst.

A series of air-stable chiral ferrocenylphosphines (LB1-LB4) were prepared and used in the asym. allylic substitution of Morita-Baylis-Hillman (MBH) adducts with phthalimide under mild reaction conditions; the (R,SFc)-ferrocenylphosphine LB4 afforded the desired amination products in moderate yields with excellent enantioselectivities. The absolute configuration of (R)-N-[2-Methoxycarbonyl-1-(2,4-dichlorophenyl)allyl]-phthalimide was confirmed by x-ray anal.

European Journal of Organic Chemistry published new progress about Allylic substitution reaction. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Application In Synthesis of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Wang, Peng; Ji, Min; Sha, Fei published the artcile< An efficient and facile process for synthesis of 4,5-dichlorothiophene-2-carboxylic acid using N-chlorosuccinimide>, Synthetic Route of 31166-29-7, the main research area is dichlorothiophene carboxylic acid preparation.

The compound 4,5-Dichlorothiophene-2-carboxylic acid was obtained from the starting material thiophene-2-carboxylic acid via esterification, chlorination and hydrolysis. The chlorination reaction was achieved using N-chlorosuccinimide as the chlorinating agent with high selectivity and yield. The advantages of this synthesis route were mild reaction conditions, simplified operational procedure and the raw materials were easy to obtain. It could be applied to industrial production

Journal of Chemical Research published new progress about Thiophenes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Synthetic Route of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kaizerman, Jacob A.; Gross, Matthew I.; Ge, Yigong; White, Sarah; Hu, Wenhao; Duan, Jian-Xin; Baird, Eldon E.; Johnson, Kirk W.; Tanaka, Richard D.; Moser, Heinz E.; Buerli, Roland W. published the artcile< DNA Binding Ligands Targeting Drug-Resistant Bacteria: Structure, Activity, and Pharmacology>, Electric Literature of 31166-29-7, the main research area is pyrrolecarboxamide trimeric aryl terminated preparation DNA binding antibacterial.

Potent DNA minor-groove binding antibacterials, e.g. I (R = aryl, heteroaryl), were designed based on the natural product distamycin A and synthesized, and their structure-activity relationship was investigated. These compounds have been shown to target A/T-rich sites within the bacterial genome and, as a result, inhibit DNA replication and RNA transcription. The optimization was focused on N-terminal aromatic heterocycles and C-terminal amines and resulted in compounds with improved in vivo tolerability and excellent in vitro antibacterial potency (MIC ≥ 0.031 μg/mL) against a broad range of Gram-pos. pathogens, including drug-resistant strains such as methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis. In a first proof-of-concept study, I (R = 3-chloro-2-thienyl) showed in vivo efficacy in a mouse peritonitis model against methicillin-sensitive S. aureus infection with an ED50 value of 30 mg/kg.

Journal of Medicinal Chemistry published new progress about Antimicrobial agents. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Electric Literature of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Profft, Elmar; Hoffmann, Hubert published the artcile< Thiophene. VIII. Sulfur derivatives of 2,3-dichloro-thiophene>, Synthetic Route of 31166-29-7, the main research area is .

The α-Cl atom of RCH2Cl (I) [R = 2,3-dichlorothien-5-yl] is very loosely held. Thus, 3.4 g. I reacted immediately in the cold with 1.7 g. KSCN in 30 ml. EtOH to give 68.8% RCH2SCN, m. 70° (petr. ether). I (51 g.) and 28 g. NH2CS2NH4 in 100 ml. EtOH gave RCH2SCSNH2 (II), yellowish crystals, m. 130° (petr. ether), almost quant. II warmed with 2N KOH gave 90.7% RCH2SH (III), b14.5136-8°. I (26.6 g.) warmed gently with KSH (from 9.4 g. KOH and H2S) in EtOH gave 56.6% crude III (which resinified on attempted distillation) and 41.4% (RCH2)2S (IV), m. 80-1°. III with Br in Et2O gave 80.5% (RCH2S)2 (V), m. 56°. III (2.5 g.) and 5 ml. H2O2 (Perhydrol) in 50 ml. HOAc at 50° gave 36.4% RCO2H, m. 196-7° (aqueous EtOH), probably via V. IV (2.8 g.) and 0.75 ml. Perhydrol in 25 ml. AcOH, after standing a few days, gave 99.2% (RCH2)2SO, m. 128° (EtOH). Similarly, 2.5 g. IV and 7 ml. Perhydrol gave 95.6% (RCH2)2SO2, m. 186° (EtOH). From I and Na mercaptides in absolute EtOH or from the Na salt of III and alkyl halides, the following RCH2SR’ (VI) were prepared in yields of 71-8% (R’ given): Et, b15 157°; Pr, b15 168°; Bu, b15 179°; Ph, m. 38° (EtOH); p-MeC6H4 (VII), m. 69° (EtOH). VI with a 4-fold excess of H2O2 in AcOH gave quant. the following RCH2SOR’ (R’ and m.p. given): Et, 92°; Pr, 106°; Bu, 82°; Ph, 137°. VII (1.2 g.) and 1 ml. Perhydrol in 10 ml. AcOH gave quant. p-MeC6H4SO2CH2R, m. 175-6° (EtOH). Portionwise addition of ClCH2COOK (from 4.8 g. acid) to an aqueous alc. solution of RCH2SK (from 10 g. III), keeping the temperature below 40°, and acidification, gave 77.5% RCH2SCH2COOH, m. 95° (petr. ether). No pure product could be isolated from the reaction of III with HNO3. I did not react with K3SO3 at room temperature; at a higher temperature (RCH2)2O was formed.

Journal fuer Praktische Chemie (Leipzig) published new progress about 31166-29-7. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Synthetic Route of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Cai, Zhengyan; Wen, Yingling; Zhang, Xuli; Liu, Zhenren; Hao, Qun published the artcile< Preparation and structural confirmation of the related substances of rivaroxaban>, Computed Properties of 31166-29-7, the main research area is rivaroxaban related substance synthesis.

According to the structural characteristics of rivaroxaban and its synthetic process, eight related substances: 5-chloro-N-[[2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide (A), N-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1, 3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide (B), 4,5-dichloro-N-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl]methyl] thiophene-2-carboxamide (C), (S)-2-[[[2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl] methyl] carbamoyl] benzoic acid (D), N1, N2-bis-[[(S)-2-oxo-3-[4-(3-oxo-4-morpholinyl) phenyl]-1, 3-oxazolidin-5-yl] methyl] phthalamide (E), 5-chloro-N-methylthiophene-2-carboxamide (F), 5-chloro-N,N-dimethylthiophene-2-carboxamide (G) and 1,3-bis-[[(S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl] methyl] urea (H), were synthesized and confirmed by 1H NMR and MS. These substances were taken as the references for the quality control of rivaroxaban.

Zhongguo Yiyao Gongye Zazhi published new progress about 31166-29-7. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Computed Properties of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Ohba, Mai; Oka, Tomoichiro; Ando, Takayuki; Arahata, Saori; Ikegaya, Asaka; Takagi, Hirotaka; Ogo, Naohisa; Owada, Kazuhiro; Kawamori, Fumihiko; Wang, Qiuhong; Saif, Linda J.; Asai, Akira published the artcile< Discovery and synthesis of heterocyclic carboxamide derivatives as potent anti-norovirus agents>, Application of C5H2Cl2O2S, the main research area is heterocyclic carboxamide preparation SAR antiviral.

In this study, synthesis, anti-norovirus activity, and structure-activity relationship (SAR) of a series of heterocyclic carboxamide derivatives I (R3 = 2-thienyl, 2-furyl, 2-thiazolyl, etc.; R4 = H, 6-Cl, 4-Br, etc.) has been described. Heterocyclic carboxamide I (R3 = 5-bromo-thiophen-2-yl; R4 = 6-F) (50% effective concentration (EC50)= 37 μM) was identified using the cytopathic effect reduction assay by the author’s screening campaign. Initial SAR studies suggested the importance of halogen substituents on the heterocyclic scaffold and identified 3,5-di-bromo-thiophene derivative (EC50 = 24 μM) and 4,6-di-benzothiazole derivative (EC50 = 5.6 μM) as more potent inhibitors than I (R3 = 5-bromo-thiophen-2-yl; R4 = 6-F). Moreover, their hybrid compound, 3,5-di-bromo-thiophen-4,6-di-fluoro-benzothiazole, showed the most potent anti-norovirus activity with a EC50 value of 0.53 μM. Further investigation suggested that the hybrid compound might inhibit intracellular viral replication or the late stage of viral infection.

Chemical & Pharmaceutical Bulletin published new progress about Antiviral agents. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Application of C5H2Cl2O2S.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Xu, Yu; Cantwell, Lucas; Molosh, Andrei I.; Plant, Leigh D.; Gazgalis, Dimitris; Fitz, Stephanie D.; Dustrude, Erik T.; Yang, Yuchen; Kawano, Takeharu; Garai, Sumanta; Noujaim, Sami F.; Shekhar, Anantha; Logothetis, Diomedes E.; Thakur, Ganesh A. published the artcile< The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents>, Synthetic Route of 31166-29-7, the main research area is GIRK1 GIRK2 channel activator preparation fear posttraumatic stress disorder; GIRK channels; PIP2; basolateral amygdala; medicinal chemistry; neurophysiology; phosphoinositide; potassium channel; small molecule; specific activator.

G-protein- gated inwardly-rectifying K+ (GIRK) channels are targets of Gi/o-protein-signaling systems that inhibit cell excitability. GIRK channels exist as homotetramers (GIRK2 and GIRK4) or heterotetramers with nonfunctional homomeric subunits (GIRK1 and GIRK3). Although they have been implicated in multiple conditions, the lack of selective GIRK drugs that discriminate among the different GIRK channel subtypes has hampered investigations into their precise physiol. relevance and therapeutic potential. Here, we report on a highly-specific, potent, and efficacious activator of brain GIRK1/2 channels. Using a chem. screen and electrophysiol. assays, we found that this activator, the bromothiophene-substituted small mol. GAT1508, is specific for brain-expressed GIRK1/2 channels rather than for cardiac GIRK1/4 channels. Computational models predicted a GAT1508- binding site validated by exptl. mutagenesis experiments, providing insights into how urea-based compounds engage distant GIRK1 residues required for channel activation. Furthermore, we provide computational and exptl. evidence that GAT1508 is an allosteric modulator of channel-phosphatidylinositol 4,5-bisphosphate interactions. Through brain-slice electrophysiol., we show that subthreshold GAT1508 concentrations directly stimulate GIRK currents in the basolateral amygdala (BLA) and potentiate baclofen-induced currents. Of note, GAT1508 effectively extinguished conditioned fear in rodents and lacked cardiac and behavioral side effects, suggesting its potential for use in pharmacotherapy for post-traumatic stress disorder. In summary, our findings indicate that the small mol. GAT1508 has high specificity for brain GIRK1/2 channel subunits, directly or allosterically activates GIRK1/2 channels in the BLA, and facilitates fear extinction in a rodent model.

Journal of Biological Chemistry published new progress about Allosteric modulators. 31166-29-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C5H2Cl2O2S, Synthetic Route of 31166-29-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics