Tag: M.W=200-250

Barn, D. R.; Caulfield, W. L.; Cottney, J.; McGurk, K.; Morphy, J. R.; Rankovic, Z.; Roberts, B. published the artcile< Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand>, Computed Properties of 42413-03-6, the main research area is tetrahydroisoquinoline sulfonamide based delta opioid ligand preparation.

A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogs of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimizing a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulfonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physicochem. properties, notably aqueous solubility The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over μ and κ opioid receptors. However the most active and selective compounds had poor aqueous solubility Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test. In the case of compound II, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, III, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, resp., at a dose of 10 mmol/kg i.v.).

Bioorganic & Medicinal Chemistry published new progress about Analgesics. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Computed Properties of 42413-03-6.

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

Lin, Lin; Lin, Guangyao; Zhou, Qingtong; Bathgate, Ross A. D.; Gong, Grace Qun; Yang, Dehua; Liu, Qing; Wang, Ming-Wei published the artcile< Design, synthesis and pharmacological evaluation of tricyclic derivatives as selective RXFP4 agonists>, HPLC of Formula: 2905-54-6, the main research area is tricyclic fused azolopyrimidine preparation RXFP4 agonist SAR docking; Molecular docking; Relaxin family peptide receptor 4; Selective agonist; Structure-activity relationship; Synthesis.

A new scaffold of tricyclic derivatives I [X = CH2, O, S, Me2C; Y = CH2, Me2C; V = CH, N, (2-ClC6H4)C, etc.; W = CH, N; R = OH, SH, MeS, pyrrolidin-1-yl] represented by compound I [X = Y = CH2, V = (2-ClC6H4)C, W = N, R = OH] was disclosed as a selective RXFP4 agonist after a high-throughput screening campaign against a diverse library of 52,000 synthetic and natural compounds Two rounds of structural modification around this scaffold were performed focusing on three parts: 2-chlorophenyl group, 4-hydroxylphenyl group and its skeleton including cyclohexane-1,3-dione and 1,2,4-triazole group. Compound I [X = S, Y = CH2, V = (2-IC6H4)C, W = N, R = OH] with a new skeleton of was thus obtained. The enantiomers of compounds I [X = Y = CH2, V = (2-ClC6H4)C, W = N, R = OH] and I [X = S, Y = CH2, V = (2-IC6H4)C, W = N, R = OH] were also resolved with their 9-(S)-conformer favoring RXFP4 agonism. Compared with compound I [X = Y = CH2, V = (2-ClC6H4)C, W = N, R = OH], compound 9-(S)-[X = S, Y = CH2, V = (2-IC6H4)C, W = N, R = OH] exhibited 2.3-fold higher efficacy and better selectivity for RXFP4 (selective ratio of RXFP4 vs. RXFP3 for 9-(S)-[X = S, Y = CH2, V = (2-IC6H4)C, W = N, R = OH] and I [X = Y = CH2, V = (2-ClC6H4)C, W = N, R = OH] were 26.9 and 13.9, resp.).

Bioorganic Chemistry published new progress about Benzaldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 2905-54-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6Cl2O2, HPLC of Formula: 2905-54-6.

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

Amberg, Alexander; Harvey, James S.; Czich, Andreas; Spirkl, Hans-Peter; Robinson, Sharon; White, Angela; Elder, David P. published the artcile< Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?>, Safety of 3-Chloro-4-methylbenzene-1-sulfonyl chloride, the main research area is mutagenesis carboxylic sulfonic acid halide.

A substantial amount of mutagenicity data on acyl/sulfonyl halides is available in the public domain, and these data are the basis for many in silico models of mutagenicity (e.g., Derek Nexus and Leadscope). A review of these data indicates that the perceived mutagenic potential of this class of compounds is based on a number of nonreproducible pos. findings in the bacterial mutagenicity assay and pos. bacterial mutagenicity data on a series of compounds where formation of reactive halodimethyl sulfides (HDMSs) in DMSO may have compromised the interpretation of the Ames data (HDMSs are typically mutagenic). The only genuine mutagenic, genotoxic, and carcinogenic compound within the 50+ acyl/sulfonyl halides described herein is dimethylcarbamic chloride, which is appropriately considered to be a potential human carcinogen. Some in silico systems, such as Derek Nexus, contain rules detailing that the activity of this class should be considered a false pos. flag for mutagenicity, and ideally, any in silico structure-activity rules for mutagenicity in other systems should likewise be addressed. The data presented here support the view that these alerts should currently be interpreted as a false pos. flag for mutagenicity and that the entire class should be viewed as a low concern from a mutagenicity perspective. The formation of these reactive HDMSs is an example of the classical Pummerer rearrangement. The chem. reactivity of this class of compounds also supports the contention that they are of limited concern from a mutagenic and carcinogenic impurity risk perspective when used in the synthesis of drug products. They can be expected to rapidly purge from any reaction sequence with generic predicted purge factors in the range from 1 × 103 to 3 × 105 per stage and hence should be effectively eliminated at the stage of introduction. We would therefore recommend avoiding the use of DMSO as the solvent for mutagenicity tests with acyl/sulfonyl halides because of the potential for false pos. results arising from DMSO reaction products, which are not relevant under aqueous, physiol. conditions. Furthermore, as indicated by the Ames test data for mesyl chloride/2-fluorobenzoyl chloride, even non-DMSO organic solvents may not be appropriate for certain members of this class (acyl/sulfonyl halides), suggesting that they may not be amenable to adequate testing in the Ames assay.

Organic Process Research & Development published new progress about Acid halides Role: ADV (Adverse Effect, Including Toxicity), BSU (Biological Study, Unclassified), BIOL (Biological Study). 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Safety of 3-Chloro-4-methylbenzene-1-sulfonyl chloride.

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

Flaherty, Daniel P.; Simpson, Denise S.; Miller, Melissa; Maki, Brooks E.; Zou, Beiyan; Shi, Jie; Wu, Meng; McManus, Owen B.; Aube, Jeffrey; Li, Min; Golden, Jennifer E. published the artcile< Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold>, Recommanded Product: 2-(Trifluoromethoxy)benzoyl chloride, the main research area is bis amide derivative preparation TASK1 potassium channel inhibitor; Bis-amide; KCNK3; Selective potassium channel inhibitor; TASK1.

TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiol. role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC50 = 16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiol. assay.

Bioorganic & Medicinal Chemistry Letters published new progress about Structure-activity relationship. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Recommanded Product: 2-(Trifluoromethoxy)benzoyl chloride.

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

Shahzadi, Tayyaba; Saleem, Rahman S. Z.; Chotana, Ghayoor A. published the artcile< Facile Synthesis of Halogen Decorated para-/meta-Hydroxybenzoates by Iridium-Catalyzed Borylation and Oxidation>, Name: Methyl 2,3-dichlorobenzoate, the main research area is para meta hydroxybenzoate preparation; benzoate ester boronic ester borylation oxidation iridium catalyst.

In this report, a facile preparation of 2,6- and 2,3-disubstituted 4/5-hydroxybenzoates by iridium-catalyzed borylation of resp. disubstituted benzoate esters followed by oxidation is described. This synthetic route allows for the incorporation of halogens in the final hydroxybenzoates with substitution patterns not readily accessible by the traditional routes of aromatic functionalization.

Synthesis published new progress about Aromatic esters Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 2905-54-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6Cl2O2, Name: Methyl 2,3-dichlorobenzoate.

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

Naik, R. G.; Wheeler, T. S. published the artcile< Reactivity of the ω-halogen atom in p-alkoxybenzyl halides: preparation of phenylacetic acids>, Formula: C8H8BrClO, the main research area is .

6-Chloropiperonal (I) and PhNH2 at 100° give 6-chloropiperonylideneaniline, m. 112°; 6-Br analog, m. 131-2°; 3-chloro-4-methoxybenzylideneaniline, m. 85°; 3-Br analog, m. 96-7°. I (25 g.), treated with 100 g. 50% NaOH and 5 cc.EtOH and kept overnight, gives 10 g. of 6-chloro-3,4-methylenedioxybenzyl alc. (II), m. 73-4°; 6-Br analog (III), m. 90°; 3-chloro-4-methoxybenzyl alc. (IV), b10 178-80°; 3-Br analog (V), m. 63-4°. Evaporation of 15 g.II in 75 cc. C6H6 saturated with HCl (at 0°) gives 14 g. of 6-chloro-3,4-methylenedioxybenzyl chloride (VI), m. 65°; shaking 10 g.II with 50 g.HBr (d. 1.69) gives 10 g. of the bromide, m. 75-6°. Similarly III gives a chloride, m. 64-5°, and a bromide, m. 94°; the chloride from IV b6 145-7° and the bromide, m. 52-3°. V yields a chloride, m. 51-2°, and a bromide, m. 61-2°. Refluxing 2 g. of VI with KI in Me2CO-H2O for 1.5 hrs. gives 1.6 g. of the iodide of II, yellow, m. 95-6°; iodide of III, m. 90-1°; of IV, m. 61-2°; of V, m. 64-5°. VI (16 g.), KCN and EtOH, shaken 24 hrs., give 9.5 g. of 6-chloropiperonylacetonitrile (VII), b15 190°, m. 70-1°; 6-Br analog, m. 71-2°; 3-chloro-p-anisylacetonitrile, m. 54-5°; 3-Br analog, m. 56-7°. Refluxing 7 g. of VII with NaOH in diluteEtOH for 8 hrs. gives 6 g. of 6-chloropiperonylicacetic acid, m. 174-5°; Me ester, m. 69-70°; Et ester, m. 60-1°; 6-Br analog, m. 190°; Et ester, m. 69-70°. 3-Chloro-p-anisylacetic acid, m. 95-6°; 3-Br analog, m. 114-15°. 3,4-Cl(MeO)C6H3CH2Cl (2.5 g.) and MeOH, refluxed 2 hrs., give 1.8 g. of 3-chloro-4-methoxybenzyl Me ether, b5 135-40°; Et ether, b10 150-5°; 3-bromo-4-methoxybenzyl Et ether, b10 155-60°; the ethers regenerate the halides on treatment with HCl-C6H6 or concentratedHBr. Heating 3,4-CH2O2C6H3CH2Br (VIII) with MeOH or EtOH for 6 hrs. gives 2,3,6,7-bismethylenedioxy-9,10-dihydroanthracene (Ewins, C. A. 4, 195); its formation is apparently catalyzed by acids, for refluxing VIII with MeOH and a little Na2CO3 gives 3,4-methylenedioxybenzyl Me ether, b10 120. The 6-halogen derivatives of VIII react with alcs. without formation of dihydroanthracenes but the oils obtained always contain more halogen than the expected ethers; the 6-NO2 derivative of VIII did not react with alcs. VI (6 g.) and 12 g.PCl5, heated 4 hrs. at 120°, give 5 g. of 6-chloro-3,4-dichloromethylenedioxybenzyl chloride (IX), b10 150-4°; addition of cold H2O after 5 min. to its solution in HCO2H gives 6-chloro-3,4-carbonyldioxybenzyl chloride (X), m. 64°. 6-Br analog of IX, b10 155-7°; of X, m. 80-1°.

Journal of the Chemical Society published new progress about Halogens. 320407-92-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrClO, Formula: C8H8BrClO.

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

Zhou, Juan; Mock, Elliot D.; Al Ayed, Karol; Di, Xinyu; Kantae, Vasudev; Burggraaff, Lindsey; Stevens, Anna F.; Martella, Andrea; Mohr, Florian; Jiang, Ming; van der Wel, Tom; Wendel, Tiemen J.; Ofman, Tim P.; Tran, Yvonne; de Koster, Nicky; van Westen, Gerard J. P.; Hankemeier, Thomas; van der Stelt, Mario published the artcile< Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family>, HPLC of Formula: 16799-05-6, the main research area is PLAAT inhibitor NAPEs NAEs anandamide alpha ketoamides SAR.

The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiol. processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified α-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the α-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301(I), a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiol. role of the PLAATs.

Journal of Medicinal Chemistry published new progress about N-Acylethanolamines Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, HPLC of Formula: 16799-05-6.

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

Naik, R. G.; Wheeler, T. S. published the artcile< Reactivity of the ω-halogen atom in p-alkoxybenzyl halides: preparation of phenylacetic acids>, Formula: C8H8BrClO, the main research area is .

6-Chloropiperonal (I) and PhNH2 at 100° give 6-chloropiperonylideneaniline, m. 112°; 6-Br analog, m. 131-2°; 3-chloro-4-methoxybenzylideneaniline, m. 85°; 3-Br analog, m. 96-7°. I (25 g.), treated with 100 g. 50% NaOH and 5 cc.EtOH and kept overnight, gives 10 g. of 6-chloro-3,4-methylenedioxybenzyl alc. (II), m. 73-4°; 6-Br analog (III), m. 90°; 3-chloro-4-methoxybenzyl alc. (IV), b10 178-80°; 3-Br analog (V), m. 63-4°. Evaporation of 15 g.II in 75 cc. C6H6 saturated with HCl (at 0°) gives 14 g. of 6-chloro-3,4-methylenedioxybenzyl chloride (VI), m. 65°; shaking 10 g.II with 50 g.HBr (d. 1.69) gives 10 g. of the bromide, m. 75-6°. Similarly III gives a chloride, m. 64-5°, and a bromide, m. 94°; the chloride from IV b6 145-7° and the bromide, m. 52-3°. V yields a chloride, m. 51-2°, and a bromide, m. 61-2°. Refluxing 2 g. of VI with KI in Me2CO-H2O for 1.5 hrs. gives 1.6 g. of the iodide of II, yellow, m. 95-6°; iodide of III, m. 90-1°; of IV, m. 61-2°; of V, m. 64-5°. VI (16 g.), KCN and EtOH, shaken 24 hrs., give 9.5 g. of 6-chloropiperonylacetonitrile (VII), b15 190°, m. 70-1°; 6-Br analog, m. 71-2°; 3-chloro-p-anisylacetonitrile, m. 54-5°; 3-Br analog, m. 56-7°. Refluxing 7 g. of VII with NaOH in diluteEtOH for 8 hrs. gives 6 g. of 6-chloropiperonylicacetic acid, m. 174-5°; Me ester, m. 69-70°; Et ester, m. 60-1°; 6-Br analog, m. 190°; Et ester, m. 69-70°. 3-Chloro-p-anisylacetic acid, m. 95-6°; 3-Br analog, m. 114-15°. 3,4-Cl(MeO)C6H3CH2Cl (2.5 g.) and MeOH, refluxed 2 hrs., give 1.8 g. of 3-chloro-4-methoxybenzyl Me ether, b5 135-40°; Et ether, b10 150-5°; 3-bromo-4-methoxybenzyl Et ether, b10 155-60°; the ethers regenerate the halides on treatment with HCl-C6H6 or concentratedHBr. Heating 3,4-CH2O2C6H3CH2Br (VIII) with MeOH or EtOH for 6 hrs. gives 2,3,6,7-bismethylenedioxy-9,10-dihydroanthracene (Ewins, C. A. 4, 195); its formation is apparently catalyzed by acids, for refluxing VIII with MeOH and a little Na2CO3 gives 3,4-methylenedioxybenzyl Me ether, b10 120. The 6-halogen derivatives of VIII react with alcs. without formation of dihydroanthracenes but the oils obtained always contain more halogen than the expected ethers; the 6-NO2 derivative of VIII did not react with alcs. VI (6 g.) and 12 g.PCl5, heated 4 hrs. at 120°, give 5 g. of 6-chloro-3,4-dichloromethylenedioxybenzyl chloride (IX), b10 150-4°; addition of cold H2O after 5 min. to its solution in HCO2H gives 6-chloro-3,4-carbonyldioxybenzyl chloride (X), m. 64°. 6-Br analog of IX, b10 155-7°; of X, m. 80-1°.

Journal of the Chemical Society published new progress about Halogens. 320407-92-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrClO, Formula: C8H8BrClO.

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

Wang, Tao; Ioannidis, Stephanos; Almeida, Lynsie; Block, Michael H.; Davies, Audrey M.; Lamb, Michelle L.; Scott, David A.; Su, Mei; Zhang, Hai-Jun; Alimzhanov, Marat; Bebernitz, Geraldine; Bell, Kirsten; Zinda, Michael published the artcile< In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors>, Application In Synthesis of 54718-39-7, the main research area is pyridinecarbonitrile pyrazolylamino arylmethylamino preparation JAK2 inhibitor.

Synthesis and biol. evaluation of a series of 6-aminopyrazolylpyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochem. screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, phys. properties and pharmacodynamic effects.

Bioorganic & Medicinal Chemistry Letters published new progress about 54718-39-7. 54718-39-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H2Cl3NO2, Application In Synthesis of 54718-39-7.

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

Nam, Nguyen-Hai; Huong, Tran Lan; Dung, Do Thi Mai; Dung, Phan Thi Phuong; Oanh, Dao Thi Kim; Park, Sang Ho; Kim, Kyungrok; Han, Byung Woo; Yun, Jieun; Kang, Jong Soon; Kim, Youngsoo; Han, Sang-Bae published the artcile< Synthesis, bioevaluation and docking study of 5-substituted phenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents>, Application of C8H6ClN3S, the main research area is thiadiazole hydroxamic acid preparation histone deacetylase inhibitor antitumor; 5-phenyl-1,3,4-thiadiazole; cytotoxicity; heterocycle; histone deacetylase (HDAC) inhibitors.

Since the first histone deacetylase (HDAC) inhibitor (Zolinza, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of the ongoing research in this area, the authors designed and synthesized a series of thiadiazole-based hydroxamic acids I [R = H, 2-Cl, 4-Me, etc.] as analogs of SAHA and evaluated their biol. activities. A number of compounds in this series, e.g. I [R = H], I [R = 2-Cl], I [R = 4-MeO], were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. These compounds were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antitumor agents. 70057-67-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6ClN3S, Application of C8H6ClN3S.

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