Category: chlorides-buliding-blocks

Wang, Shuai published the artcileDiscovery of [1,2,4]triazolo[1,5-a]pyrimidine derivatives as new bromodomain-containing protein 4 (BRD4) inhibitors, COA of Formula: C8H6ClF3, the publication is Chinese Chemical Letters (2020), 31(2), 418-422, database is CAplus.

Targeting bromodomain-containing protein 4 (BRD4) has been proved to be an effective strategy for cancer therapy. To date, numerous BRD4 inhibitors and degraders have been identified, some of which have advanced into clin. trials. In this work, a focused library of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives were discovered to be able to inhibit BRD4. WS-722 inactivated BRD4 (BD1/BD2), BRD2 (BD1/BD2) and BRD3 (BD1/BD2) broadly with the IC₅₀ values less than 5μmol/L. Besides, WS-722 inhibited growth of THP-1 cells with an IC₅₀ value of 3.86μmol/L. Like (+)-JQ1, WS-722 inhibited BRD4 in a reversible manner and enhanced protein stability. Docking studies showed that WS-722 occupied the central acetyl-lysine (Kac) binding cavity and formed a hydrogen bond with Asn140. In THP-1 cells, WS-722 showed target engagement to BRD4. Cellular effects of WS-722 on THP-1 cells were also examined, showing that WS-722 could block c-MYC expression, induce G0/G1 phase arrest and p21 up-regulation, and promote differentiation of THP-1 cells. BRD4 inhibition by WS-722 resulted in cell apoptosis and up-regulated expression of cleaved caspased-3/7 and PARP in THP-1 cell lines. The [1,2,4]triazolo[1,5-a]pyrimidine is a new template for the development of new BRD4 inhibitors.

Chinese Chemical Letters published new progress about 939-99-1. 939-99-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Benzyl chloride,Benzene, name is 1-(Chloromethyl)-4-(trifluoromethyl)benzene, and the molecular formula is C8H15ClN2, COA of Formula: C8H6ClF3.

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

Cui, Shuzhen published the artcileSynthesis and characterisation of photochromic dithienylcyclopentene liquid crystal with thermal irreversibility, Recommanded Product: 5-Chloro-3-[2-(5-chloro-2-methylthien-3-yl)cyclopent-1-en-1-yl]-2-methylthiophene, the publication is Liquid Crystals (2016), 43(6), 803-810, database is CAplus.

A series of photochromic liquid crystal dithienylcyclopentene derivatives I (n = 4, 5, 6, 7) was synthesized from the initial material 2-chloro-5-methylthiophene. They were characterized by ¹H NMR, high resolution mass spectrometer, differential scanning calorimetry (DSC) and polarized optical microscopy (POM) with a hot stage. All of them exhibited excellent photochem. reversible isomerization between the open-ring form and the closed-ring form in both organic solvents and LC media, resulting in the color change between colorless and purple under different light irradiations. The typical textures from POM showed that their isomers both had nematic phase and smectic phase with different colors. These compounds with bent shape were more sensitive to light than those of diarylethenes reported.

Liquid Crystals published new progress about 219537-97-0. 219537-97-0 belongs to chlorides-buliding-blocks, auxiliary class Fused/Partially Saturated Cycles,Cyclopentenes, name is 5-Chloro-3-[2-(5-chloro-2-methylthien-3-yl)cyclopent-1-en-1-yl]-2-methylthiophene, and the molecular formula is C15H14Cl2S2, Recommanded Product: 5-Chloro-3-[2-(5-chloro-2-methylthien-3-yl)cyclopent-1-en-1-yl]-2-methylthiophene.

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

Liu, Pengfei published the artcileMultipathways for the Synthesis of Fused Bicyclic 2-Aminothiazolyl Compounds Tuned by Ring Size, Product Details of C7H7ClN2S, the publication is Synlett (2014), 25(19), 2797-2801, database is CAplus.

A new methodol. for the synthesis of fused bicyclic 2-aminothiazolyl compounds was developed, using cyclocondensation of aromatic thioureas with α,β-epoxy cycloketones in alc. under microwave irradiation without any catalyst. The product distribution is related to the ring size of α,β-epoxy cycloketones. Mechanistic studies suggest that the reactions share analogous bicyclic dihydroxy intermediates but undergo different further reactions to give diverse products.

Synlett published new progress about 3696-23-9. 3696-23-9 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Thiourea,Amine,Benzene,Amide, name is 1-(4-Chlorophenyl)thiourea, and the molecular formula is C7H7ClN2S, Product Details of C7H7ClN2S.

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

Wang, Jing published the artcileMichael acceptor in gambogic acid-Its role and application for potent antitumor agents, Recommanded Product: trimethyloxosulphonium chloride, the publication is Bioorganic & Medicinal Chemistry Letters (2015), 25(14), 2844-2848, database is CAplus and MEDLINE.

Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clin. application as an anticancer agent. Moreover, the 6-OH forms an intramol. hydrogen bond with 8-C=O, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-mol. hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a Me group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.

Bioorganic & Medicinal Chemistry Letters published new progress about 5034-06-0. 5034-06-0 belongs to chlorides-buliding-blocks, auxiliary class Salt,Aliphatic hydrocarbon chain, name is trimethyloxosulphonium chloride, and the molecular formula is C17H18N3NaO3S, Recommanded Product: trimethyloxosulphonium chloride.

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

Feng, Yanli published the artcileNew photochromic bisthienylethene derivatives containing carbazole, SDS of cas: 219537-97-0, the publication is Journal of Physical Organic Chemistry (2007), 20(11), 968-974, database is CAplus.

Some new photochromic bisthienylethene (BTE) derivatives containing carbazole were synthesized by Suzuki coupling method. All compounds were characterized by ¹H NMR spectra, ¹³C NMR, mass spectra, etc. Their optical, photochromic, and electrochem. properties were described. Moreover, their two-photon absorption (TPA) properties were investigated both in open and closed forms, finding observable distinction in the TPA of the ring-open and ring-closed forms. These compounds could be used as two-photon switches and for the potential applications in three-dimensional optical storage.

Journal of Physical Organic Chemistry published new progress about 219537-97-0. 219537-97-0 belongs to chlorides-buliding-blocks, auxiliary class Fused/Partially Saturated Cycles,Cyclopentenes, name is 5-Chloro-3-[2-(5-chloro-2-methylthien-3-yl)cyclopent-1-en-1-yl]-2-methylthiophene, and the molecular formula is C15H14Cl2S2, SDS of cas: 219537-97-0.

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

Cheng, Hua published the artcileDiscovery of 1,2,4-triazole-1,3-disulfonamides as dual inhibitors of mitochondrial complex II and complex III, Related Products of chlorides-buliding-blocks, the publication is New Journal of Chemistry (2015), 39(9), 7281-7292, database is CAplus.

Respiratory chain succinate-ubiquinone oxidoreductase (SQR or complex II) and ubihydroquinone-cytochrome (cyt) c oxidoreductase (cyt bc₁ or complex III) have been demonstrated as the promising targets of numerous antibiotics and fungicides. As a continuation of our research work on the development of new fungicides, a series of 1,2,4-triazole-1,3-disulfonamide derivatives with dual functions targeting both SQR and cyt bc₁ were designed and synthesized by coupling diverse di-Ph ether moieties with triazolesulfonamide units. These newly synthesized compounds were characterized by elemental analyses, ¹H NMR and ESI-MS spectrometry. The in vitro assay indicated that most of the synthesized compounds displayed good inhibition against porcine succinate-cytochrome reductase (SCR) with IC₅₀ values ranging from 3.2 to 81.8 μM, revealing much higher activity than that of the com. control amisulbrom whose IC₅₀ value is 93.0 μM. Further evaluation against the resp. SQR and cyt bc₁ indicated that most compounds exhibited SQR-inhibiting activity as well as cyt bc₁-inhibiting activity, but the inhibition potency against SQR is much higher than that against cyt bc₁, showing that the SCR inhibition might be contributed greatly by the SQR inhibition. The further antibacterial evaluation against Xanthomonas oryzae pv. oryzae revealed that four compounds showed excellent potency at the concentration of 20 μg mL^-1. In particular, compounds (I) and (II) exhibited much better antibacterial activity than the com. control bismerthiazol in terms of their EC₅₀. Impressively, II has an EC₉₀ of 33.62 μg mL^-1, more than 10-fold higher than that of bismerthiazol.

New Journal of 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, Related Products of chlorides-buliding-blocks.

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

Bourquin, J. P. published the artcileSyntheses in the phenothiazine family. II. N-Substituted phenothiazinethiol derivatives, Formula: C5H13Cl2N, the publication is Helvetica Chimica Acta (1958), 1072-108, database is CAplus.

cf. C.A. 52, 18423d. 2-(N-Methyl-2-pyrrolidyl)ethanol (31.0 g.) in 200 ml. CHCl₃ treated with HCl 10 min. at 10°, 59.0 g. SOCl₂ added, after 2 hrs. at 70° the mixture concentrated, treated with 160 ml. 3N NaOH, extracted with Et₂O, and the dried extracts distilled gave 90% 2-(N-methyl-2-pyrrolidyl)-1-chloroethane (I), b₁₁ 65-6°; picrate, m. 133-5° (EtOH). BuNHMe (60.9 g.) and 54.6 g. Br(CH₂)₃Cl in boiling Et₂O 24 hrs. gave 68% BuMeN(CH₂)₃Cl, b₁₃ 71-2°; picrate, m. 94-6° (EtOH). BrCH₂CHMeCH₂Cl (68.6 g.), 36.0 g. Me₂NH, and 20 ml. C₆H₆ heated in an autoclave at 110° 7 hrs., 100 ml. H₂O and 320 ml. 10% HCl added, and the mixture extracted with 250 ml. Et₂O and 140 ml. 30% NaOH gave 68% Me₂NCH₂CHMeCH₂Cl, b₁₁ 35-6°. To 50.0 g. N-methylpiperazine in 150 ml. MeOH was added 37.7 g. propylene oxide, the mixture boiled 3 hrs., and distilled giving 70% N-methyl-N’-(2-hydroxypropyl)piperazine (II), b₁₁ 91-3°. II (50.7 g.) in 250 ml. C₆H₆ saturated with HCl, 78.2 g. SOCl₂ added, the mixture refluxed 5 hrs. then concentrated, 100 ml. H₂O and 120 ml. 30% NaOH added, the mixture extracted with 600 ml. C₆H₆, and the extract distilled gave 60% N-methyl-N’-(2-chloropropyl)piperazine, b₁₁ 87-9°; di-HCl salt, m. 233-5° (EtOH). N-Methylpiperazine (46.8 g.) and 40 g. BrCH₂CHMeCH₂Cl in 120 ml. refluxing Et₂O 24 hrs. gave 30% N-methyl-N’-(3-chloro-2-methylpropyl)piperazine, b₁₁ 99-100°; di-HCl salt, m. 234-6° (MeOH). Similarly, 233 g. N-benzylpiperazine and 104 g. Br(CH₂)₃Cl in 370 ml. Et₂O 48 hrs. gave 75% N-benzyl-N’-(3-chloropropyl)piperazine, b_0.01 132-6°; di-HCl salt, m. 249-51° (absolute EtOH). 2-(Methylthio)phenothiazine (III) (16.65 g.), 3.18 g. NaNH₂, and 100 ml. absolute xylene refluxed 3 hrs., 10.0 g. I in 10 ml. absolute xylene added during 1.5 hrs., after refluxing 3 hrs. and cooling 5 g. NH₄Cl and 150 ml. H₂O added, the xylene layer extracted with 115 ml. 15% tartaric acid, 35 ml. concentrated NaOH added, and the freed base extracted with 100 ml. C₆H₆ gave 85% 10-[2-(N-methyl-2-pyrrolidyl)ethyl]-2-(methylthio)phenothiazine, b_0.008 209°; tartrate, sintered 70°, m. 115°. Similarly prepared were the following 10-[2-(N-methyl-2-pyrrolidyl)ethyl]-2-(alkylthio)phenothiazines (alkyl groups given): Et, b_0.01 213° (tartrate-0.5-H₂O, sintered 65°, m. 90°); iso-Pr, b_0.008 217° (tartrate-0.5H₂O, sintered 70°, m. 90°); Bu, b_0.01 225° (tartrate-0.5H₂O, sintered 60°, m. 75°). 10-[2-(N-Methyl-2-piperidyl)ethyl]-2-(alkylthio)phenothiazines (alkyl groups given): Et (IV) [80% from 18.89 g. 2-(ethylthio)phenothiazine (V) and 14.7 g. 2-(N-methyl-2-piperidyl)-1-chloroethane], b_0.008, m. 57-9° (iso-PrOH) (tartrate, sintered 70°, decompose 135°); Pr, b_0.01 247° (tartrate, sintered 70°, decompose 120°); iso-Pr, b_0.05 223°, m. 73-5° (tartrate, sintered 70°, decompose 120°); Bu, b_0.005 227°; iso-Bu, b_0.003 215°; sec-Bu, b_0.007 215°; n-hexyl, b_0.015 235°; PhCH₂ (VI), b_0.01 246° (tartrate-0.5-H₂O, sintered 75°, m. 105°). 10-(N-Methyl-3-piperidylmethyl)-2-alkylphenothiazines (alkyl groups given): Me [60% from 50.0 g. III and 33.8 g. N-methyl-3-(chloromethyl)piperidine], b_0.01 207° [HCl salt, sintered 110°, decompose 124-6° (Me₂CO); tartrate-0.5H₂O, sintered 75°, decompose 140° (EtOAc); oxalate, decompose 182-4° (absolute EtOH)]; Et, b_0.01 222° (tartrate, sintered 75°, m. 140°); Pr, b_0.01 225°, sintered 85°, m. 145°; iso-Pr, b_0.01 216° (tartrate-0.5H₂O, sintered 75°, decompose 140°); Bu, b_0.01 223° (tartrate, sintered 80°, decompose 100°); iso-Bu, b_0.005 207° (tartrate-0.5H₂O, sintered 85°, m. 120°); sec-Bu, b_0.005 206°, tartrate-0.5H₂O, sintered 80°, m. 110°); PhCH₂, b_0.007 236° (tartrate-H₂O, sintered 90°, m. 120°). 10-(3-Dimethylaminopropyl)-2-(alkylthio)phenothiazines (alkyl group given): Et (80-5% from 20.0 g. V and 11.3 g. Me₂N(CH₂)₃Cl), b_0.008 200° [tartrate, sintered 110°, m. 117-9° (absolute EtOH)]; Pr, b_0.02 227° (tartrate-0.5H₂O, sintered 55°, decompose 90°); iso-Pr, b_0.01 198° (tartrate-0.5H₂O, sintered 60°, decompose 90°; oxalate, decompose 206-8°); Bu, b_0.005 202°; iso-Bu, b_0.004 195°; sec-Bu, b_0.006 189°; PhCH₂, b_0.01 224° (tartrate, sintered 65°, m. 85°). 10-Dialkylaminoalkyl-2-(methylthio)phenothiazines (dialkylaminoalkyl groups given): Me₂NCH₂CH₂ (85% from 50.0 g. III and 22.0 g. Me₂NCH₂CH₂Cl), b_0.01 195-6°, m. 72-4° (iso-PrOH) [HCl salt, m. 175-7° (absolute EtOH)]; Et₂NCH₂CH₂, b_0.01 198° (HCl salt, m. 160-2°); Et₂NCHMeCH₂, b_0.01 182° (HCl salt, sintered 194°, m. 202-4°); 2-(N-pyrrolidyl)ethyl, b_0.01 219-21°, m. 73-5° (HCl salt, m. 170-2°); 2-(N-methyl-N’-piperazyl)ethyl, b_0.02 228-30°, m. 85-7° (di-HCl salt, decompose 243-5°); 3-(N-piperidyl)propyl, b_0.05 235-7° (tartrate, sintered 65°, decompose 100°; methobromide, sintered 165°, m. 178-80°); 3-(N-benzyl-N’-piperazyl)propyl, m. 82-4° (di-HCl salt, sintered 225°, decompose 236-8°); 3-(N-morpholyl)propyl, b_0.03 240-2°, m. 100-2° (HCl salt, sintered 146°, m. 152-4°); 2-(N-pyrrolidyl)propyl, b_0.015 204° (HCl salt, m. 177-9°); 2-(N-methyl-N’-piperazyl)propyl, b_0.01 211° (di-HCl salt-0.5H₂O, sintered 210°, m. 224-6°). 10-Dialkylaminoalkyl-2-(isopropylthio)phenothiazines: Me₂NCH₂CH₂, b_0.015 189° (HCl salt, m. 182-4°); Et₂NCH₂CH₂, b_0.01 187° (HCl salt, m. 162-4°);

Helvetica Chimica Acta published new progress about 4584-49-0. 4584-49-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Salt,Amine,Aliphatic hydrocarbon chain, name is 2-Chloro-N,N-dimethylpropan-1-amine hydrochloride, and the molecular formula is C5H13Cl2N, Formula: C5H13Cl2N.

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

Spinnato, Davide published the artcileA Photochemical Organocatalytic Strategy for the α-Alkylation of Ketones by using Radicals, Formula: C8H6ClF3, the publication is Angewandte Chemie, International Edition (2020), 59(24), 9485-9490, database is CAplus and MEDLINE.

Reported herein is a visible-light-mediated radical approach to the α-alkylation of ketones. This method exploits the ability of a nucleophilic organocatalyst to generate radicals upon S_N2-based activation of alkyl halides and blue light irradiation The resulting open-shell intermediates are then intercepted by weakly nucleophilic silyl enol ethers, which would be unable to directly attack the alkyl halides through a traditional two-electron path. The mild reaction conditions allowed functionalization of the α position of ketones with functional groups that are not compatible with classical anionic strategies. In addition, the redox-neutral nature of this process makes it compatible with a cinchona-based primary amine catalyst, which was used to develop a rare example of enantioselective organocatalytic radical α-alkylation of ketones. Thus, e.g., treatment of acetophenone O-TBS silyl enol ether with chloroacetonitrile afforded I (91%) in presence of dithiocarbonyl catalyst II using blue LED irradiation and TFA or TBAF workup.

Angewandte Chemie, International Edition published new progress about 939-99-1. 939-99-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Benzyl chloride,Benzene, name is 1-(Chloromethyl)-4-(trifluoromethyl)benzene, and the molecular formula is C9H10O3S, Formula: C8H6ClF3.

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

Wang, Dengjin published the artcileOne-Carbon Chain Extension of Esters to α-Chloroketones: A Safer Route without Diazomethane, Name: trimethyloxosulphonium chloride, the publication is Journal of Organic Chemistry (2004), 69(5), 1629-1633, database is CAplus and MEDLINE.

The reaction of a variety of Me esters with dimethylsulfoxonium methylide at 0-25 °C affords the chain-extended β-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding α-chloro ketones. This sequence has been utilized to convert the Me esters of CBZ-protected alanine and valine to the anti N-protected α-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine Me ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chem. provides a practical route to α-chloroketones that avoids the use of toxic and explosive diazomethane.

Journal of Organic Chemistry published new progress about 5034-06-0. 5034-06-0 belongs to chlorides-buliding-blocks, auxiliary class Salt,Aliphatic hydrocarbon chain, name is trimethyloxosulphonium chloride, and the molecular formula is C11H14O2, Name: trimethyloxosulphonium chloride.

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