Month: December 2022

Tanaka, Yuta published the artcileDiscovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore, Formula: C6H4ClNO2, the publication is Journal of Medicinal Chemistry (2022), 65(5), 4270-4290, database is CAplus and MEDLINE.

Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher’s disease and has been suggested as a potential target for treating Parkinson’s disease. Herein, authors report the discovery of novel brain-penetrant GCS inhibitors. Assessment of the structure-activity relationship revealed a unique pharmacophore in this series. The lipophilic ortho-substituent of aromatic ring A and the appropriate directionality of aromatic ring B were key for potency. Optimization of the absorption, distribution, metabolism, elimination, toxicity (ADMETox) profile resulted in the discovery of T-036, a potent GCS inhibitor in vivo. Pharmacophore-based scaffold hopping was performed to mitigate safety concerns associated with I. The ring opening of I resulted in another potent GCS inhibitor with a lower toxicol. risk, II, which reduced glucosylceramide in a dose-dependent manner in the plasma and cortex of mice. Finally, authors discuss the structural aspects of the compounds that impart a unique inhibition mode and lower the cardiovascular risk.

Journal of Medicinal Chemistry published new progress about 6313-54-8. 6313-54-8 belongs to chlorides-buliding-blocks, auxiliary class Pyridine,Chloride,Carboxylic acid, name is 2-Chloroisonicotinic acid, and the molecular formula is C19H14Cl2, Formula: C6H4ClNO2.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Ishikawa, Tomoyasu published the artcileDesign and Synthesis of Novel Human Epidermal Growth Factor Receptor 2 (HER2)/Epidermal Growth Factor Receptor (EGFR) Dual Inhibitors Bearing a Pyrrolo[3,2-d]pyrimidine Scaffold, Recommanded Product: 3-Chloro-4-fluoronitrobenzene, the publication is Journal of Medicinal Chemistry (2011), 54(23), 8030-8050, database is CAplus and MEDLINE.

Dual inhibitors of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) have been investigated for breast, lung, gastric, prostate, and other cancers; one, lapatinib, is currently approved for breast cancer. To develop novel HER2/EGFR dual kinase inhibitors, we designed and synthesized pyrrolo[3,2-d]pyrimidine derivatives, e.g. I, capable of fitting into the receptors’ ATP binding site. Among the prepared compounds, I showed potent HER2 and EGFR (HER1) inhibitory activities as well as tumor growth inhibitory activity. The X-ray cocrystal structures of I with both HER2 and EGFR demonstrated that I interacts with the expected residues in their resp. ATP pockets. Furthermore, reflecting its good oral bioavailability, I exhibited potent in vivo efficacy in HER2-overexpressing tumor xenograft models. On the basis of these findings, we report I (TAK-285) as a promising candidate for clin. development as a novel HER2/EGFR dual kinase inhibitor.

Journal of Medicinal Chemistry published new progress about 350-30-1. 350-30-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Nitro Compound,Benzene, name is 3-Chloro-4-fluoronitrobenzene, and the molecular formula is C6H3ClFNO2, Recommanded Product: 3-Chloro-4-fluoronitrobenzene.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Purohit, Priyank published the artcileC-O Bond Activation by Nickel-Palladium Hetero-Bimetallic Nanoparticles for Suzuki-Miyaura Reaction of Bioactive Heterocycle-Tethered Sterically Hindered Aryl Carbonates, Category: chlorides-buliding-blocks, the publication is ACS Catalysis (2017), 7(4), 2452-2457, database is CAplus.

Ni-Pd binary nanoclusters are reported for the activation of the C-O bond for Suzuki-Miyaura cross-coupling of bioactive heterocycle-tethered sterically hindered aryl carbonates with aryl boronic acids. The reaction does not take place in the presence of either the Pd or Ni salts/complexes or the individual Pd or Ni nanoparticles, indicating ensembling cooperativity between the Pd and Ni nanoparticles in activating the C-O bond.

ACS Catalysis published new progress about 480438-56-0. 480438-56-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Ether,Boronic Acids,Boronic acid and ester, name is 3-Chloro-4-isopropoxyphenylboronic acid, and the molecular formula is C9H12BClO3, Category: chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Tsuchida, Kouhei published the artcileConstruction of Chiral Tri- and Tetra-Arylmethanes Bearing Quaternary Carbon Centers: Copper-Catalyzed Enantioselective Propargylation of Indoles with Propargylic Esters, Application In Synthesis of 21286-54-4, the publication is Angewandte Chemie, International Edition (2016), 55(33), 9728-9732, database is CAplus and MEDLINE.

Copper-catalyzed enantioselective propargylation of indoles with propargylic esters and sequential Huisgen cycloaddition with azides lead to the construction of chiral triarylmethanes, bearing a quaternary carbon center, with high to excellent enantioselectivities. The result described herein can be used in the enantioselective preparation of a tetraarylmethane.

Angewandte Chemie, International Edition published new progress about 21286-54-4. 21286-54-4 belongs to chlorides-buliding-blocks, auxiliary class Chiral,Chloride,Sulfonyl chlorides,Aliphatic cyclic hydrocarbon,Ketone, name is ((1S,4R)-7,7-Dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonyl chloride, and the molecular formula is C8H10O2, Application In Synthesis of 21286-54-4.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Kodolov, V. I. published the artcileFrequency shift of the phosphorus:oxygen bond in organophosphorus compounds, Recommanded Product: Diethyltrichloromethylphosphonate, the publication is Trudy Instituta Khimii, Akademiya Nauk SSSR, Ural’skii Filial (1966), 99-101, database is CAplus.

Ir spectra were examined in the 1150-1350-cm.-1 region for (EtO)2PHO, MeP(O)(OEt)2, CH2:CHCH2P(O)(OEt)2, PhP(O)(OEt)2, CCl3P(O)(OEt)2, and PhPOCl2. The exptl. found values of vibrational frequencies of the P(O) bond agreed better with the values calculated by the L. C. Thomas equation (1964) than those calculated according to Griffin (1960).

Trudy Instituta Khimii, Akademiya Nauk SSSR, Ural’skii Filial published new progress about 866-23-9. 866-23-9 belongs to chlorides-buliding-blocks, auxiliary class Aliphatic Chain, name is Diethyltrichloromethylphosphonate, and the molecular formula is C5H10Cl3O3P, Recommanded Product: Diethyltrichloromethylphosphonate.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Kodolov, V. I. published the artcilePossibilities for calculating stretching vibrational frequencies of the phosphorus=oxygen-group for some alkyl(aryl) phosphonates and aryl phosphates, Name: Diethyltrichloromethylphosphonate, the publication is Zhurnal Prikladnoi Spektroskopii (1967), 7(3), 382-6, database is CAplus.

Spectra of alkyl and aryl phosphates and of arylphosphates were measured in the liquid phase and in Nujol in the region 900-1900 cm.-1 The exptl. P:O group frequencies γPO were compared with values obtained by the calculation of γPO from Griffin (γPO = 1198 + 16.8 Σπ) and Thomas (γPO = 930 + 40 Σσ*) equations, where σ* = Taft constant and π = the electronegativity of the substituent. The comparison of exptl. and calculated γPO showed in phosphonates a better agreement if the Thomas equation were applied. The lower difference is explained by higher accuracy owing to π value application. The σ* is not precise because the interaction mass substituent is not taken into account. Tables give the charges, bond lengths and angles, electrostatic forces, and σk values for H, Me, CCl3, CHCl2, CH2Cl, Et, and Ph substituents. The differences between exptl. and calculated γPO were the same by the application of both equations in arylphosphates because only an insignificant effect of substituent polarity can occur in the neighborhood of the phosphate group.

Zhurnal Prikladnoi Spektroskopii published new progress about 866-23-9. 866-23-9 belongs to chlorides-buliding-blocks, auxiliary class Aliphatic Chain, name is Diethyltrichloromethylphosphonate, and the molecular formula is C5H10Cl3O3P, Name: Diethyltrichloromethylphosphonate.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Katsev, A. M. published the artcileStudy of interactions between cationic surface-active antiseptics and serum albumin by bacterial bioluminescence, Application of N1,N10-Bis(2-((2-isopropyl-5-methylcyclohexyl)oxy)-2-oxoethyl)-N1,N1,N10,N10-tetramethyldecane-1,10-diaminium chloride, the publication is Klinicheskaya Laboratornaya Diagnostika (2002), 39-41, database is CAplus and MEDLINE.

Human serum albumin binding of cationic surface-active antiseptics was studied using a Photobacterium phosphoreum K3 strain isolated in the Black Sea. Binding of cationic surface-active proteins to serum albumin led to disappearance of toxic and antibacterial characteristics of miramistin, ethonium, and decametoxin, but not chlorhexidine. The activity of chlorohexidine was reduced by 45-8% in the presence of albumin. Albumin binding capacity towards miramistin was 7.0-8.7%, towards ethonium 8.2-10%, and towards decametoxin 2.4-3%.

Klinicheskaya Laboratornaya Diagnostika published new progress about 38146-42-8. 38146-42-8 belongs to chlorides-buliding-blocks, auxiliary class Achiral Phase-Transfer Catalysts, name is N1,N10-Bis(2-((2-isopropyl-5-methylcyclohexyl)oxy)-2-oxoethyl)-N1,N1,N10,N10-tetramethyldecane-1,10-diaminium chloride, and the molecular formula is C38H74Cl2N2O4, Application of N1,N10-Bis(2-((2-isopropyl-5-methylcyclohexyl)oxy)-2-oxoethyl)-N1,N1,N10,N10-tetramethyldecane-1,10-diaminium chloride.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Su, Helen C. F. published the artcileSynthesis of possible cancer chemotherapeutic compounds based on enzyme approach. III. 1,2,3-Oxadithiolane 2-oxide, Product Details of C4H8Cl2S2, the publication is Journal of Organic Chemistry (1961), 4993-5, database is CAplus.

1,2,3-Oxadithiolane 2-oxide (I) was prepared from mercaptoethanol (II) and SOCl₂ in CHCl₃. The 5-Me derivative (III) was prepared by this method. Attempted preparation of the 5-Ph derivative under the same conditions led only to 2,5-diphenyl-p-dithiane (IV). Treatment of I with K₂CO₃ gave CO₂, SO₂, and ethylene sulfide. Bromination of I with Br yielded bis(2-bromoethyl) disulfide (V) and with N-bromosuccinimide, yielded N-(2-bromoethylthio)succinimide (VI). II (156 g.) in 150 ml. CHCl₃ and 262 g. SOCl₂ added dropwise into 200 ml. CHCl₃ at room temperature and stirred 5 hrs. gave 176 g. I, b₃ 77-9°, n²⁰_D 1.5771, 22.3% 2-chloro-2′-mercaptodiethyl sulfide, b₄ 91-4°, n²⁰_D 1.5653, 1.5% p-dithiane, flakes, m. 111-12°, and a residual paste which, treated with hot concentrated H₂SO₄-HNO₃, gave a gray sponge. Isopropenyl acetate (20 g.) treated dropwise with 16.7 g. thiolacetic acid and the mixture heated 2 hrs. gave 74% 1-acetoxythioisopropyl acetate (VII), b_0.65-0.70 56.5-8.0°, n³³_D 1.4635. VII refluxed with 1% MeOH-HCl for 7 hrs. and evaporated gave 2-hydroxypropyl mercaptan, b_46-7 75-9°, n³⁰_D 1.4818. III, prepared in 3 hrs. at 28-30° by the same method used for I, b_1.7-2.1 72-85°, m. 39-9.5°; distillation of the residue gave a dark liquid, b_1.6-2.1 82-120°. Attempted redistillation of this product led to severe decomposition Styrene oxide (36 g.) added in 5 hrs. to 30 g. Ba(OH)₂ in 75% alc. saturated with H₂S below 30°, H₂S passed in for 1 hr. longer and the mixture saturated with CO₂ and extracted gave 76.8% 1-phenyl-2-mercaptoethanol (VIII), b_3.7-4.1 124.5-7.0°, n²⁷_D 1.5803. VIII (31.5 g.) and 35.7 g. SOCl₂ added simultaneously to CHCl₃ at 25-30°, stirred 5 hrs., evaporated, and the liquid treated with C in CHCl₃, concentrated, and triturated with Et₂O gave IV, flakes, m. 212-14°. The solvent filtrate further concentrated gave rhombic crystals of S, m. 113-15°. Equimolar amounts of I and K₂CO₃ heated to the point where gas was evolved gave almost quant. yields of CO₂ and SO₂ and 2.3 ml. ethylene sulfide, b. 55-6°, n²⁰_D 1.4821. I (12.4 g.) was added dropwise to a preheated flask at 270°/130-5 mm. and the products distilled to give S and unchanged I, H₂O and a rubbery substance, and a mixture of SO₂, H₂O, and more rubbery product. I (12.4 g.) in 100 ml. CCl₄ treated at -5° with 16 g. Br in 20 ml. CCl₄, and the mixture stirred 5 hrs. at room temperature and distilled gave 4.5 g. V, b_0.5-.055 103-6°, n¹⁹_D 1.6190. N-Bromosuccinimide (17.8 g.) added portionwise to 12.4 g. I in 100 ml. CCl₄ at 15-20° and the mixture heated 6 hrs. at 25-30° gave 8 g. VI, m. 89-90.5°. The liquid was evaporated to give a small amount of V. I (28.3 g.) containing 0.1 g. Bz₂O₂ treated at -5° with Cl, stirred 3 hrs. at 0°, then overnight at room temperature, and distilled gave 63% V. I (12.4 g.) and 13.4 g. N-chlorosuccinimide refluxed 8 hrs. in 100 ml. CCl₄ gave succinimide. The CCl₄ solution afforded some I and 1.5 g. bis(2-chloroethyl) disulfide, b_0.8 80-7°, n²⁰_D 1.5634. III treated with Br in CCl₄ as above gave bis(g-bromopropyl) disulfide, b_0.8 113-14°, n²²_D 1.5805. Infrared spectra were given for the above compounds

Journal of Organic Chemistry published new progress about 1002-41-1. 1002-41-1 belongs to chlorides-buliding-blocks, auxiliary class Aliphatic Chain, name is 1,2-Bis(2-chloroethyl)disulfane, and the molecular formula is C8H5F3O2S, Product Details of C4H8Cl2S2.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Akapo, S. O. published the artcileThe production of stable, uniform reverse phases for liquid chromatography by oligomeric synthesis, Related Products of chlorides-buliding-blocks, the publication is Journal of Liquid Chromatography (1991), 14(2), 217-36, database is CAplus.

The use of oligomeric synthesis for the preparation of reverse phases by a fluidized bed technique is described. Reverse phases comprising 1-10 oligomers were synthesized and the phys. and chromatog. properties of each phase examined The nature of the interactions were investigated by measuring the excess free enthalpies of absorption of a homologous series of aromatic hydrocarbons and aromatic esters from retention measurements taken at different temperatures It is shown that a reverse phase comprising ≥5 oligomers behaves as a true dispersive phase, has consistent and predictable retentive properties, and is far more stable to acid conditions than the normal type reverse phase.

Journal of Liquid Chromatography published new progress about 14799-93-0. 14799-93-0 belongs to chlorides-buliding-blocks, auxiliary class Aliphatic Chain, name is Dichloro(methyl)(octyl)silane, and the molecular formula is C9H20Cl2Si, Related Products of chlorides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Sonoshita, Masahiro published the artcileA whole-animal platform to advance a clinical kinase inhibitor into new disease space, Quality Control of 32333-53-2, the publication is Nature Chemical Biology (2018), 14(3), 291-298, database is CAplus and MEDLINE.

Synthetic tailoring of approved drugs for new indications is often difficult, as the most appropriate targets may not be readily apparent, and therefore few roadmaps exist to guide chem. Here, we report a multidisciplinary approach for accessing novel target and chem. space starting from an FDA-approved kinase inhibitor. By combining chem. and genetic modifier screening with computational modeling, we identify distinct kinases that strongly enhance (‘pro-targets’) or limit (‘anti-targets’) whole-animal activity of the clin. kinase inhibitor sorafenib in a Drosophila medullary thyroid carcinoma (MTC) model. We demonstrate that RAF-the original intended sorafenib target-and MKNK kinases function as pharmacol. liabilities because of inhibitor-induced transactivation and neg. feedback, resp. Through progressive synthetic refinement, we report a new class of ‘tumor calibrated inhibitors’ with unique polypharmacol. and strongly improved therapeutic index in fly and human MTC xenograft models. This platform provides a rational approach to creating new high-efficacy and low-toxicity drugs.

Nature Chemical Biology published new progress about 32333-53-2. 32333-53-2 belongs to chlorides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Chloride,Sulfonyl chlorides,Benzene, name is 4-Chloro-3-(trifluoromethyl)benzenesulfonyl Chloride, and the molecular formula is C8H10S, Quality Control of 32333-53-2.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics