Month: February 2023

Free energy perturbation (FEP)-guided scaffold hopping was written by Wu, Deyan;Zheng, Xuehua;Liu, Runduo;Li, Zhe;Jiang, Zan;Zhou, Qian;Huang, Yue;Wu, Xu-Nian;Zhang, Chen;Huang, Yi-You;Luo, Hai-Bin. And the article was included in Acta Pharmaceutica Sinica B in 2022.SDS of cas: 4457-67-4 This article mentions the following:

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chem. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theor. binding potencies ΔGFEP between ligands and their target, which were more consistent with the exptl. binding potencies ΔGEXP (the mean absolute deviations |ΔGFEP – ΔGEXP| < 2 kcal/mol) than those ΔGMM-PBSA or ΔGMM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational mol. design and drug discovery. In the experiment, the researchers used many compounds, for example, 1-Bromo-4-methoxybutane (cas: 4457-67-4SDS of cas: 4457-67-4).

1-Bromo-4-methoxybutane (cas: 4457-67-4) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon–bromine bond is electrophilic in nature. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.SDS of cas: 4457-67-4

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Synthesis of highly active juvenile hormone analogs, juvocimene I and II, from the oil of sweet basil, Ocimum basilicum L was written by Nishida, Ritsuo;Bowers, William S.;Evans, Philip H.. And the article was included in Journal of Chemical Ecology in 1984.Safety of 1-(3-Bromopropyl)-4-methoxybenzene This article mentions the following:

Juvocimene I and II (I, R = CH:CMe₂, 3,3-dimethyl-2-oxiranyl, resp.) were isolated from the oil of O. basilicum and their structures determined by synthesis from p-MeOC₆H₄(CH₂)₃Br and Me₂C:CHCH(OAc)CH₂CHMeEt. In the experiment, the researchers used many compounds, for example, 1-(3-Bromopropyl)-4-methoxybenzene (cas: 57293-19-3Safety of 1-(3-Bromopropyl)-4-methoxybenzene).

1-(3-Bromopropyl)-4-methoxybenzene (cas: 57293-19-3) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Safety of 1-(3-Bromopropyl)-4-methoxybenzene

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Steering Siglec-sialic acid interactions on living cells using bioorthogonal chemistry was written by Buell, Christian;Heise, Torben;van Hilten, Niek;Pijnenborg, Johan F. A.;Bloemendal, Victor;Gerrits, Lotte;Kers-Rebel, Esther D.;Ritschel, Tina;den Brok, Martijn H.;Adema, Gosse J.;Boltje, Thomas J.. And the article was included in Angewandte Chemie, International Edition in 2017.Formula: C8H7BrO2 This article mentions the following:

Sialic acid sugars that terminate cell-surface glycans form the ligands for the sialic acid binding Ig-like lectin (Siglec) family, which are immunomodulatory receptors expressed by immune cells. Interactions between sialic acid and Siglecs regulate the immune system, and aberrations contribute to pathologies like autoimmunity and cancer. Sialic acid/Siglec interactions between living cells are difficult to study owing to a lack of specific tools. Here, we report a glycoengineering approach to remodel the sialic acids of living cells and their binding to Siglecs. Using bioorthogonal chem., a library of cells with more than sixty different sialic acid modifications was generated that showed dramatically increased binding toward the different Siglec family members. Rational design reduced cross-reactivity and led to the discovery of three selective Siglec-5/14 ligands. Furthermore, glycoengineered cells carrying sialic acid ligands for Siglec-3 dampened the activation of Siglec-3⁺ monocytic cells through the NF-κB and IRF pathways. In the experiment, the researchers used many compounds, for example, 3-(Bromomethyl)benzoic acid (cas: 6515-58-8Formula: C8H7BrO2).

3-(Bromomethyl)benzoic acid (cas: 6515-58-8) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. When the molecular ion is detected, the bromine and chlorine isotope patterns are very distinct, but caution is to be exercised for certain mixed chlorinated/brominated compounds, which can look similar to homohalogen patterns.Formula: C8H7BrO2

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Characteristics of metabolic stability and the cell permeability of 2-pyrimidinyl-piperazinyl-alkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione with antidepressant- and anxiolytic-like activities was written by Zagorska, Agnieszka;Partyka, Anna;Bucki, Adam;Kolaczkowski, Marcin;Jastrzebska-Wiesek, Magdalena;Czopek, Anna;Siwek, Agata;Gluch-Lutwin, Monika;Bednarski, Marek;Bajda, Marek;Jonczyk, Jakub;Piska, Kamil;Koczurkiewicz, Paulina;Wesolowska, Anna;Pawlowski, Maciej. And the article was included in Chemical Biology & Drug Design in 2019.Synthetic Route of C13H14BrNO2 This article mentions the following:

A series of 2-pyrimidinyl-piperazinyl-alkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5-HT_1A, 5-HT₇, and phosphodiesterases PDE4 and PDE10. The most potent compound 2-pyrimidinyl-1-piperazinyl-butyl-imidazo[2,1-f]purine-2,4-dione (4b) behaved as strong and selective antagonist of 5-HT_1A. Mol. modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands’ affinity and potency in the 5-HT_1A receptor. Compound 4b in silico models demonstrated drug-likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Exptl. obtained value of apparent permeability coefficient P_app for 4b in parallel artificial permeability assay indicates the possibility of binding weakly to plasma proteins and high intestinal absorption fraction. Evaluation of the antidepressant- and anxiolytic-like activities of 4b revealed both activities at the same dose of 1.25 mg/kg and seemed to be specific. The antidepressant and/or anxiolytic properties of 4b may be related to its first-pass effect. In the experiment, the researchers used many compounds, for example, N-(5-Bromopentyl)phthalimide (cas: 954-81-4Synthetic Route of C13H14BrNO2).

N-(5-Bromopentyl)phthalimide (cas: 954-81-4) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Synthetic Route of C13H14BrNO2

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Synthesis and Biological Evaluation of Quinoxaline Derivatives for PET Imaging of the NMDA Receptor was written by Milicevic Sephton, Selena;Vetterli, Peter T.;Pedani, Valentina;Cermak, Stjepko;Chiotellis, Aristeidis;Roscales, Sylvia;Mueller Herde, Adrienne;Schibli, Roger;Auberson, Yves P.;Ametamey, Simon M.. And the article was included in Helvetica Chimica Acta in 2017.Synthetic Route of C7H6BrF This article mentions the following:

Due to the biol. complexity of the N-methyl-D-aspartate receptor (NMDAR), the development of a positron emission tomog. radiotracer for the imaging of NMDAR has met with limited success. Recent studies have established the presence of GluN2A subunit of the NMDAR in the heart and its role in the regulation of intracellular calcium levels. In our efforts to develop an imaging agent for the GluN2A subunit, we designed three new compounds based on a quinoxaline scaffold. The synthesis of the analogs was based on a two-step Kabachnik-Fields reaction in sequence with Suzuki cross-coupling and acid hydrolysis. They exhibited comparable high binding affinity values below 5 nM. A two-step radiolabeling procedure was successfully developed for the synthesis of [¹⁸F]I. [¹⁸F]I was obtained in a modest overall radiochem. yield of 5.5 ± 4.2%, a good specific radioactivity of 254 ± 158 GBq/μmol, and a radiochem. purity > 99%. While two compounds showed comparable binding affinity towards NMDAR, sluggish radiolabeling, prevented their further evaluation. For [¹⁸F]I, in vitro autoradiog. on rat heart slices demonstrated heterogeneous but unspecific accumulation, whereas for the brain a high in vitro specificity towards NMDAR, could be demonstrated. In the experiment, the researchers used many compounds, for example, 3-Bromo-4-fluorotoluene (cas: 452-62-0Synthetic Route of C7H6BrF).

3-Bromo-4-fluorotoluene (cas: 452-62-0) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. alpha-Bromoesters are employed in the Reformatsky reaction for the synthesis of beta-hydroxyesters. When the molecular ion is detected, the bromine and chlorine isotope patterns are very distinct, but caution is to be exercised for certain mixed chlorinated/brominated compounds, which can look similar to homohalogen patterns.Synthetic Route of C7H6BrF

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Aryl Bis-Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium falciparum was written by Thelemann, Jonas;Illarionov, Boris;Barylyuk, Konstantin;Geist, Julie;Kirchmair, Johannes;Schneider, Petra;Anthore, Lucile;Root, Katharina;Trapp, Nils;Bacher, Adelbert;Witschel, Matthias;Zenobi, Renato;Fischer, Markus;Schneider, Gisbert;Diederich, Francois. And the article was included in ChemMedChem in 2015.Recommanded Product: 615-55-4 This article mentions the following:

2-Methylerythritol 2,4-cyclodiphosphate synthase (IspF) is an essential enzyme for the biosynthesis of isoprenoid precursors in plants and many human pathogens. The protein is an attractive target for the development of anti-infectives and herbicides. Using a photometric assay, a screen of 40,000 compounds on IspF from Arabidopsis thaliana afforded sym. aryl bis-sulfonamides that inhibit IspF from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC₅₀ values in the micromolar range. The ortho-bis-sulfonamide structural motif is essential for inhibitory activity. The best derivatives obtained by parallel synthesis showed IC₅₀ values of 1.4 μM against PfIspF and 240 nM against AtIspF. Substantial herbicidal activity was observed at a dose of 2 kg ha^-1. Mol. modeling studies served as the basis for an in silico search targeted at the discovery of novel, non-sym. sulfonamide IspF inhibitors. The designed compounds were found to exhibit inhibitory activities in the double-digit micromolar IC₅₀ range. In the experiment, the researchers used many compounds, for example, 3,4-Dibromoaniline (cas: 615-55-4Recommanded Product: 615-55-4).

3,4-Dibromoaniline (cas: 615-55-4) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Recommanded Product: 615-55-4

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Remote Directed Isocyanation of Unactivated C(sp³)-H Bonds: Forging Seven-Membered Cyclic Ureas Enabled by Copper Catalysis was written by Zhang, Hongwei;Tian, Peiyuan;Ma, Lishuang;Zhou, Yulu;Jiang, Cuiyu;Lin, Xufeng;Xiao, Xiao. And the article was included in Organic Letters in 2020.Reference of 14425-64-0 This article mentions the following:

Reported herein is an unprecedented copper-catalyzed site-selective δ-C(sp³)-H bonds activation of aliphatic sulfonamides for constructing the synthetically useful seven-membered N-heterocycles. A key to success is the use of in-situ-formed amide radicals, to activate the inert C(sp³)-H bond, and inexpensive TMSNCO, as a coupling reagent under mild conditions. To the best of our knowledge, this represents the first use of alkylamine derivatives as a five-membered synthon to prepare a seven-membered N-heterocycles. In the experiment, the researchers used many compounds, for example, 1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0Reference of 14425-64-0).

1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Reference of 14425-64-0

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Synthesis of 2-bromo- and 2-phenyl-neo-confused porphyrins was written by Almejbel, Arwa S.;Lash, Timothy D.. And the article was included in Organic & Biomolecular Chemistry in 2020.Application of 881676-32-0 This article mentions the following:

Neo-confused porphyrins (neo-CPs), porphyrin isomers with a 1,3-connected pyrrolic subunit, are aromatic structures with a CNNN coordination core. Previously, examples of neo-CPs with fused benzo units or electron-withdrawing ester substituents have been described. In this paper, two new examples of neo-CPs are reported that lack a fused aromatic unit or an ester moiety, but instead have a bromo or Ph substituent on the neo-confused ring. Acid-catalyzed condensation of suitably substituted 1,2′-dipyrrylmethane dialdehydes with a 2,2′-dipyrrylmethane, followed by oxidation with aqueous ferric chloride solutions, afforded the neo-CPs in 40-45% yield. These porphyrin analogs had slightly reduced diatropic ring currents and slowly decomposed in solution The related palladium(II) and nickel(II) complexes proved to be very unstable, even though the diatropicity of the macrocycle was enhanced. This study shows that stabilizing substituents are necessary for investigations into this class of porphyrinoids. Attempts to prepare imidazole versions of neo-CPs were unsuccessful. In the experiment, the researchers used many compounds, for example, 5-Bromo-1H-pyrrole-3-carbaldehyde (cas: 881676-32-0Application of 881676-32-0).

5-Bromo-1H-pyrrole-3-carbaldehyde (cas: 881676-32-0) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Application of 881676-32-0

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Structure-Based Design and Development of Functionalized Mercaptoguanine Derivatives as Inhibitors of the Folate Biosynthesis Pathway Enzyme 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus was written by Dennis, Matthew L.;Chhabra, Sandeep;Wang, Zhong-Chang;Debono, Aaron;Dolezal, Olan;Newman, Janet;Pitcher, Noel P.;Rahmani, Raphael;Cleary, Ben;Barlow, Nicholas;Hattarki, Meghan;Graham, Bim;Peat, Thomas S.;Baell, Jonathan B.;Swarbrick, James D.. And the article was included in Journal of Medicinal Chemistry in 2014.Electric Literature of C9H11BrO This article mentions the following:

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), an enzyme from the folate biosynthesis pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin and is a yet-to-be-drugged antimicrobial target. Building on our previous discovery that 8-mercaptoguanine (8MG) is an inhibitor of Staphylococcus aureus HPPK (SaHPPK), we have identified and characterized the binding of an S8-functionalized derivative (3). X-ray structures of both the SaHPPK/3/cofactor analog ternary and the SaHPPK/cofactor analog binary complexes have provided insight into cofactor recognition and key residues that move over 30 Å upon binding of 3, whereas NMR measurements reveal a partially plastic ternary complex active site. Synthesis and binding anal. of a set of analogs of 3 have identified an advanced new lead compound (11) displaying >20-fold higher affinity for SaHPPK than 8MG. A number of these exhibited low micromolar affinity for dihydropteroate synthase (DHPS), the adjacent, downstream enzyme to HPPK, and may thus represent promising new leads to bienzyme inhibitors. In the experiment, the researchers used many compounds, for example, 1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0Electric Literature of C9H11BrO).

1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Electric Literature of C9H11BrO

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Effect of intermolecular interaction on the reaction of bromination in the binary system benzene-nitrobenzene was written by Cheshko, F. F.;Novikova, L. N.;Shevchenko, O. I.. And the article was included in Zhurnal Obshchei Khimii in 1957.Synthetic Route of C10H13BrO This article mentions the following:

Bromination of a 2:5 molar mixture of C₆H₆ and PhNO₂ 4 hrs. on a steam bath with 0.3 mole Br per 0.36 mole C₆H₆ occurred rapidly and in 90 min. gave 33.1% PhBr without any Br₂C₆H₄; a kinetic curve of the reaction was shown. In CCl₄ the reaction failed to take place after 4 hrs. When the solvent was omitted, the reaction was very slow for 1.5 hrs., then proceeded at an appreciable rate and gave 10.3% PhBr in 4 hrs. The reaction in PhBr was less rapid than in PhNO₂ but more rapid than without a solvent and gave 15.3% PhBr in 4 hrs. The solvating or complexing action of PhNO₂ on C₆H₆ accounted for the activation of the reaction described above. In the experiment, the researchers used many compounds, for example, 1-(3-Bromopropyl)-4-methoxybenzene (cas: 57293-19-3Synthetic Route of C10H13BrO).

1-(3-Bromopropyl)-4-methoxybenzene (cas: 57293-19-3) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. alpha-Bromoesters are employed in the Reformatsky reaction for the synthesis of beta-hydroxyesters. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Synthetic Route of C10H13BrO

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary