Month: January 2023

Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor was written by Maloney, Patrick R.;Khan, Pasha;Hedrick, Michael;Gosalia, Palak;Milewski, Monika;Li, Linda;Roth, Gregory P.;Sergienko, Eduard;Suyama, Eigo;Sugarman, Eliot;Nguyen, Kevin;Mehta, Alka;Vasile, Stefan;Su, Ying;Stonich, Derek;Nguyen, Hung;Zeng, Fu-Yue;Novo, Arianna Mangravita;Vicchiarelli, Michael;Diwan, Jena;Chung, Thomas D. Y.;Smith, Layton H.;Pinkerton, Anthony B.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.Category: chlorides-buliding-blocks This article mentions the following:

The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the âˆ?30,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid and benzodiazepinone receptors (<50/<70%I at 10 μM). The synthetic methodol., development of structure-activity relationship (SAR), and initial in vitro pharmacol. characterization are also presented. In the experiment, the researchers used many compounds, for example, 3-Cyanobenzoyl chloride (cas: 1711-11-1Category: chlorides-buliding-blocks).

3-Cyanobenzoyl chloride (cas: 1711-11-1) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Category: chlorides-buliding-blocks

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

Reaction of substituted benzenes and chloral. VIII. Fluorescent substances, by-products of reduction of DDT-type compounds with zinc dust and glacial acetic acid was written by Yasue, Masaichi;Takai, Yoshiharu. And the article was included in Yakugaku Zasshi in 1959.Electric Literature of C8H7ClO3 This article mentions the following:

[5,2-Me(MeO)C₆H₃]₂CHCl₃ (10 g.) in 200 ml. AcOH treated portionwise with 50 g. Zn, heated 3 hrs., the solution filtered, the filtrate concentrated in vacuo, the residue extracted with Et₂O, the Et₂O removed, and the residue in petr. ether cooled gave 4.1 g. [5,2-Me(MeO)C₆H₃]₂CHMe, m. 56-7°, and the mother liquor concentrated gave 0.3 g. fluorescent substance (I), columns, m. 157°. Oxidation of I with KMnO₄ yielded 5,2-Me(MeO)C₆H₃CO₂H, m. 67°, suggesting that the I is a stilbene derivative The reduction product of [5,2-Cl(MeO)C₆H₃]₂CHCCl₃ also showed fluorescence but the fluorescent compound was not isolated. KMnO₄ oxidation of the crude product yielded a nonfluorescent ethane compound and 5,2-Cl(MeO)C₆H₃CO₂H. The same treatment of Ph₂CHCCl₃ yielded a small amount of stilbene as the by-product. In the experiment, the researchers used many compounds, for example, 5-Chloro-2-methoxybenzoic acid (cas: 3438-16-2Electric Literature of C8H7ClO3).

5-Chloro-2-methoxybenzoic acid (cas: 3438-16-2) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Electric Literature of C8H7ClO3

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

2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D₂ dopaminergic ligands was written by Parraga, Javier;Cabedo, Nuria;Andujar, Sebastian;Piqueras, Laura;Moreno, Laura;Galan, Abraham;Angelina, Emilio;Enriz, Ricardo D.;Ivorra, Maria Dolores;Sanz, Maria Jesus;Cortes, Diego. And the article was included in European Journal of Medicinal Chemistry in 2013.Safety of 2-(3-Methoxyphenyl)acetyl chloride This article mentions the following:

Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurol. disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson’s disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D₂ dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D₁ and D₂ DR and establish the structure-activity relation (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D₁ and D₂ DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D₂ DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D₁ DR but dramatically reduced the selectivity for D₂ DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homolog with an OH group in position 11 (9e) (250 fold for D₂ DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A mol. modeling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, compound I (2,3,9-trihydroxy-THPB) behave as D₂ DR agonist since serine residues cluster are crucial for agonist binding and receptor activation. In the experiment, the researchers used many compounds, for example, 2-(3-Methoxyphenyl)acetyl chloride (cas: 6834-42-0Safety of 2-(3-Methoxyphenyl)acetyl chloride).

2-(3-Methoxyphenyl)acetyl chloride (cas: 6834-42-0) belongs to organic chlorides. An organic chloride is an organic compound containing at least one covalently bonded atom of chlorine. Their wide structural variety and divergent chemical properties lead to a broad range of names and applications. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Safety of 2-(3-Methoxyphenyl)acetyl chloride

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

Chemical constitution and the dissociation constants of monocarboxylic acids. XV. Steric effects in substituted nitrobenzoic acids was written by Dippy, J. F. J.;Hughes, S. R. C.;Laxton, J. W.. And the article was included in Journal of the Chemical Society in 1956.Recommanded Product: 2-Chloro-6-nitrobenzoic acid This article mentions the following:

The dissociation constants were determined conductimetrically in H₂O at 25° for 2,3-(O₂N)₂C₆H₃CO₂H (I), 2,4-(O₂N)₂C₆H₃CO₂H (II), 2,5-(O₂N)₂C₆H₃CO₂H (III), 2,6-(O₂N)₂C₆H₃CO₂H (IV), 3,4-(O₂N)₂C₆H₃CO₂H (V), 3,5-(O₂N)₂C₆H₃CO₂H (VI), 2,3-Cl(O₂N)C₆H₃CO₂H (VII), 2,4-Cl(O₂N)C₆H₃CO₂H (VIII), 2,5-Cl(O₂N)C₆H₃CO₂H (IX), 2,6-Cl(O₂N)C₆H₃CO₂H (X), 2,6-Br(O₂N)C₆H₃CO₂H (XI), 2,4,6-(O₂N)₃C₆H₂CO₂H (XII), 4,3,5-Me(O₂N)₂C₆H₂CO₂H (XIII), 2-O₂NC₆H₄OH (XIV), 2,6-(O₂N)₂C₆H₃OH (XV), and 2,4,6-(O₂N)₃C₆H₂OH (XVI). The results shed light on the operation of steric effects in the BzOH system. V was prepared from 3,4-(O₂N)₂C₆H₃Me by oxidation with KMnO₄ in 50% H₂SO₄. Refluxing 2,4-(O₂N)₂C₆H₃Me with equal volumes of fuming HNO₃ and AcOH gave II. I and XII were prepared from PhEt and 2,4,6-(O₂N)₃C₆H₂Me, resp. All acids were recrystallized repeatedly from conductivity H₂O to constant m.p. after drying several weeks in desiccators, and equivalents were confirmed by alkalimetry. Measurements were made with an improved bridge network and equipment already described (loc. cit.). Solutions were prepared individually by weight at each concentration The thermodynamic dissociation constants were calculated along the usual lines. A solvent correction was applied in the derivation of K for XIV. Fuoss’s extrapolation method (cf. C.A. 29, 2824⁸), in which measurements of the equivalent conductivity of the aqueous acid are used, were employed for the determination of Λ₀. Dissociation constants × 10³ found were: I, 14.1; II, 37.6; III, 23.9; IV, 72.5; V, 1.52; VI, 1.50; VII, 9.51; VIII, 10.9; IX, 6.80; X, 45.5; XI, 42.4; XII, 222; and XIII, 1.07. For the phenols the dissociation constants were: XIV, 5.9 × 10^-8; XV, 1.97 × 10^-4; and XVI, 1.96 × 10^-1. The values of Λ₀ exhibit none of the regularities usual in related monocarboxylic acids. This is perhaps connected with the fact that in this series anomalies are introduced by large steric factors which are likely to influence variously and anomalously the solvation characteristics of the different anions. In the experiment, the researchers used many compounds, for example, 2-Chloro-6-nitrobenzoic acid (cas: 5344-49-0Recommanded Product: 2-Chloro-6-nitrobenzoic acid).

2-Chloro-6-nitrobenzoic acid (cas: 5344-49-0) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Recommanded Product: 2-Chloro-6-nitrobenzoic acid

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

Montmorillonite K-10 and montmorillonite KSF as new and reusable catalysts for conversion of amines to N-(tert-butyl carbamates) was written by Chankeshwara, Sunay V.;Chakraborti, Asit K.. And the article was included in Journal of Molecular Catalysis A: Chemical in 2006.SDS of cas: 18437-66-6 This article mentions the following:

Montmorillonite K-10 and montmorillonite KSF were found to be new and reusable catalysts for chemoselective conversion of amines to N-t-Boc derivatives at room temperature under solvent-free conditions without competitive formation of isocyanate, urea and N,N-di-t-Boc. Various aromatic, heteroaromatic and aliphatic amines afforded N-(t-Bu carbamates) in excellent yields on treatment with (Boc)₂O after 5 min-2 h. Chiral amine and esters of α-amino acids afforded optically pure N-t-Boc derivatives in high yields. The catalytic efficiency of montmorillonite KSF was marginally inferior to that of montmorillonite K-10. In the experiment, the researchers used many compounds, for example, tert-Butyl (4-chlorophenyl)carbamate (cas: 18437-66-6SDS of cas: 18437-66-6).

tert-Butyl (4-chlorophenyl)carbamate (cas: 18437-66-6) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.SDS of cas: 18437-66-6

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

Rhodium-Catalyzed Ring Expansion of Azetidines via Domino Conjugate Addition/N-Directed α-C(sp³)-H Activation was written by Sun, Ling-Zhi;Yang, Xuan;Li, Nan-Nan;Li, Meng;Ouyang, Qin;Xie, Jian-Bo. And the article was included in Organic Letters in 2022.Electric Literature of C19H15Cl This article mentions the following:

A facile synthetic method for 4-aryl-4,5-dihydropyrrole-3-carboxylates was developed, with a rhodium-catalyzed ring expansion strategy from readily available 2-(azetidin-3-ylidene) acetates and aryl boronic acids. Mechanistic investigations suggest a novel domino “conjugate addition/N-directed α-C(sp³)-H activation” process. The asym. catalytic synthesis of the 4-aryl-4,5-dihydropyrrole-3-carboxylate was realized by using QuinoxP* (91-97% ee). The synthetic utility of this protocol was demonstrated by the synthesis of 3,4-disubstituted or 2,3,4-trisubstituted pyrrolidines with excellent diastereoselectivities. In the experiment, the researchers used many compounds, for example, (Chloromethanetriyl)tribenzene (cas: 76-83-5Electric Literature of C19H15Cl).

(Chloromethanetriyl)tribenzene (cas: 76-83-5) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Electric Literature of C19H15Cl

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

Discovery of 3-Quinazolin-4(3H)-on-3-yl-2,N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors was written by Dong, Jiaqiang;Huang, Jingjie;Zhou, Ji;Tan, Ye;Jin, Jing;Tan, Xi;Wang, Bei;Yu, Tao;Wu, Chengde;Chen, Shuhui;Wang, Tie-Lin. And the article was included in ACS Medicinal Chemistry Letters in 2020.Formula: C7H4ClF3O2S This article mentions the following:

Phosphoinositide 3-kinases (PI3Ks) mediate a series of events related to cell growth, proliferation, survival, and differentiation. Overexpression of PI3Ks can lead to the dysregulation of cell homeostasis and cause tumorigenesis. In this study, rationally designed compounds were investigated as PI3Kα-selective inhibitors. Our efforts culminated in the discovery of a series of quinazolin-4(3H)-one derivatives with 2-substituted-N-methylpropanamide substitutions as PI3Kα-selective inhibitors. The best compound, I, has PI3Kα enzymic and cellular IC₅₀ values of 1.8 and 12.1 nM, resp. It exhibits biochem. selectivities for PI3Kα over PI3Kβ/δ/γ of 150/7.72/7.67-fold and cellular selectivities of 115/15.1/>826-fold, resp. Compound I is 59% orally bioavailable with a dose-normalized AUC of 3090 nM. These effects translated into in vivo conditions, as I significantly time- and dose-dependently inhibited phosphorylation of Akt in BT-474 s.c. xenograft mice and inhibited tumor growth. In the experiment, the researchers used many compounds, for example, 3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6Formula: C7H4ClF3O2S).

3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Formula: C7H4ClF3O2S

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

Reaction of phenylmagnesium bromide with halomethyl and α-bromobenzyl benzoates was written by Mizuch, K. G.;Gel’fer, Ts. M.. And the article was included in Doklady Akademii Nauk SSSR in 1950.Application In Synthesis of Chloromethyl benzoate This article mentions the following:

Addition of 4.25 g. ClCH₆OBz to cold PhMgBr (from 2.9 g. Mg and 18.8 g. PhBr) in Et₂O below 5°, followed by standing in an ice bath 1 hr. and refluxing 30 min. gave, after the usual treatment with NH₄Cl solution, 1.5 g. Ph₂, 2.5 g. (92%) PhCH₂OH, b₁₅ 97-100°, and 5.95 g. (91.5%) Ph₃COH; no BzOH was isolated. Similarly, BrCH₂OBz gave 86% PhCH₂OH and 87.5% Ph₃COH, without any BzOH. PhMgBr (from 30.2 g. PhBr and 4.7 g. Mg) in Et₂O with 11.64 g. PhCHBrOBz gave 60% Ph₃COH, 1.6 g. Ph₂, 3.2 g. Ph₂CHOH (43.5%), 1.0 g. (10.4%) Ph₃CH, 1.47 g. (11%) tetraphenolethane, m. 209.6-10.6° (from AcOH), and 0.61 g. (12.6%) BzOH. Similar reaction of PhMgBr (from 1.76 g. Mg and 12.3 g. PhBr) with 5.76 g. Ph₂CHOBz gave 3.25 g. (88.2%) Ph₂CHOH and 4.73 g. Ph₃COH (90.9%), as well as 0.9 g. Ph₂. The results are explained, at least in part, by the reaction of RMgX with the 1st C atom of the ROH involved in the ester structure, caused principally by the presence of sufficiently electrophilic groups in the vicinity of the ester link. In the experiment, the researchers used many compounds, for example, Chloromethyl benzoate (cas: 5335-05-7Application In Synthesis of Chloromethyl benzoate).

Chloromethyl benzoate (cas: 5335-05-7) belongs to organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.Application In Synthesis of Chloromethyl benzoate

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

Synthesis and biological activity of substituted 1,2,4-triazolo[1,5-c]pyrimidine derivatives was written by Chen, Chaonan;Chen, Qiong;Yang, Guangfu. And the article was included in Youji Huaxue in 2009.Recommanded Product: 697-73-4 This article mentions the following:

A method for the synthesis of the title compounds is reported here. Several 2-(benzyloxy)-7-chloro-5-(methylthio)[1,2,4]triazolo[1,5-c]pyrimidine derivatives and 2-phenoxy[1,2,4]triazolo[1,5-c]pyrimidine derivatives were designed and synthesized using substituted 4-(hydrazinyl)pyrimidine as starting material. All compounds were confirmed by elemental anal., MS, NMR. A preliminary bioassay indicated that some compounds display good herbicidal and fungicidal activity. In the experiment, the researchers used many compounds, for example, 2-(Chloromethyl)-1,3-difluorobenzene (cas: 697-73-4Recommanded Product: 697-73-4).

2-(Chloromethyl)-1,3-difluorobenzene (cas: 697-73-4) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.Recommanded Product: 697-73-4

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

Synthesis, biological activity, and docking studies of new acetylcholinesterase inhibitors of the bispyridinium type was written by Kapkova, Petra;Stiefl, Nikolaus;Suerig, Ulf;Engels, Bernd;Baumann, Knut;Holzgrabe, Ulrike. And the article was included in Archiv der Pharmazie (Weinheim, Germany) in 2003.Synthetic Route of C7H5ClF2 This article mentions the following:

A novel series of acetylcholinesterase (AChE) inhibitors of the bispyridinium type was synthesized and the inhibitory activity against AChE and butyrylcholinesterase (BChE) measured. In essence, the substitution pattern influenced the inhibitory potency against AChE, where the most active bispyridiniumoxime (TMB-4) was bisbenzyl substituted followed by monobenzyl substituted, bismethyl substituted, and unsubstituted derivatives of TMB-4. Hence, the bisbenzyl ether of TMB-4 was further investigated. In order to obtain diverse lipophilic and electronic properties for these bisbenzyl bispyridinium derivatives (so-called DUO series), the lateral ring substitution was systematically varied. The lowest IC₅₀ value against AChE found thus far in the DUO series was 0.34 μM. Docking studies were carried out to elucidate the differences in biol. activity. A general binding mode for nearly all compounds could be identified by these investigations. In this binding mode, the docked ligands span the narrow, deeply buried active-site gorge, interacting with Trp84 at the bottom of the gorge, Tyr334 or Phe331 halfway down the gorge, and Trp279 at the peripheral anionic site at the mouth of the gorge. For specific ligands, addnl. interactions were found which helped to explain their deviating activity. Based on the promising characteristics of the novel acetylcholinesterase inhibitors presented, a series of structurally related, optimized candidates will be developed. In the experiment, the researchers used many compounds, for example, 2-(Chloromethyl)-1,3-difluorobenzene (cas: 697-73-4Synthetic Route of C7H5ClF2).

2-(Chloromethyl)-1,3-difluorobenzene (cas: 697-73-4) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids.While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available. Alkyl chlorides readily undergo attack by nucleophiles.Synthetic Route of C7H5ClF2

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