Tag: 200-300

Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a Pyridopyridazinone pan-RAF Kinase Inhibitor was written by Huestis, Malcolm P.;Durk, Matthew R.;Eigenbrot, Charles;Gibbons, Paul;Hunsaker, Thomas L.;La, Hank;Leung, Dennis H.;Liu, Wendy;Malek, Shiva;Merchant, Mark;Moffat, John G.;Muli, Christine S.;Orr, Christine J.;Parr, Brendan T.;Shanahan, Frances;Sneeringer, Christopher J.;Wang, Weiru;Yen, Ivana;Yin, Jianping;Rudolph, Joachim;Siu, Michael. And the article was included in ACS Medicinal Chemistry Letters in 2021.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline This article mentions the following:

Structure-based optimization of a set of aryl urea RAF inhibitors has led to the identification of Type II pan-RAF inhibitor GNE-9815 (7)(I), which features a unique pyrido[2,3-d]pyridazin-8(7H)-one hinge-binding motif. With minimal polar hinge contacts, the pyridopyridazinone hinge binder moiety affords exquisite kinase selectivity in a lipophilic efficient manner. The improved physicochem. properties of GNE-9815 provided a path for oral dosing without enabling formulations. In vivo evaluation of GNE-9815 in combination with the MEK inhibitor cobimetinib demonstrated synergistic MAPK pathway modulation in an HCT116 xenograft mouse model. To the best of our knowledge, GNE-9815 is among the most highly kinase-selective RAF inhibitors reported to date. In the experiment, the researchers used many compounds, for example, 5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline).

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) 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 principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Design and Synthesis of Orally Bioavailable Aminopyrrolidinone Histone Deacetylase 6 Inhibitors was written by Lin, Xianfeng;Chen, Wenming;Qiu, Zongxing;Guo, Lei;Zhu, Wei;Li, Wentao;Wang, Zhanguo;Zhang, Weixing;Zhang, Zhenshan;Rong, Yiping;Zhang, Meifang;Yu, Lingjie;Zhong, Sheng;Zhao, Rong;Wu, Xihan;Wong, Jason C.;Tang, Guozhi. And the article was included in Journal of Medicinal Chemistry in 2015.COA of Formula: C8H6BrFO2 This article mentions the following:

Histone deacetylase 6 (HDAC6) removes the acetyl group from lysine residues in a number of non-histone substrates and plays important roles in microtubule dynamics and chaperone activities. There is growing interest in identifying HDAC6-selective inhibitors as chem. biol. tools and ultimately as new therapeutic agents. Herein we report the design, synthesis, and phenotypic screening of a novel class of 3-aminopyrrolidinone-based hydroxamic acids as HDAC6 inhibitors. In particular, the α-methyl-substituted enantiomer I (3-S) showed significant in-cell tubulin acetylation (Tub-Ac) with an EC₅₀ of 0.30 μM but limited impact on p21 levels at various concentrations In enzyme inhibition assays, I demonstrated high selectivity for HDAC6 with an IC₅₀ of 0.017 μM and selectivity indexes of 10 against HDAC8 and over 4000 against HDAC1-3 isoforms. Moreover, I has suitable drug metabolism and pharmacokinetics properties compared with other hydroxamic acid-based HDAC inhibitors, warranting further biol. studies and development as a selective HDAC6 inhibitor. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2COA of Formula: C8H6BrFO2).

Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2) 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. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.COA of Formula: C8H6BrFO2

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Synthesis of Polybrominated Diphenyl Ethers and Their Capacity to Induce CYP1A by the Ah Receptor Mediated Pathway was written by Chen, Guosheng;Konstantinov, Alexandre D.;Chittim, Brock G.;Joyce, Elizabeth M.;Bols, Niels C.;Bunce, Nigel J.. And the article was included in Environmental Science and Technology in 2001.Application of 615-55-4 This article mentions the following:

Polybrominated di-Ph ethers (PBDEs) have become widely distributed as environmental contaminants due to their use as flame retardants. Their structural similarity to other halogenated aromatic pollutants has led to speculation that they might share toxicol. properties such as hepatic enzyme induction. In this work we synthesized a number of PBDE congeners, studied their affinity for rat hepatic Ah receptor through competitive binding assays, and determined their ability to induce hepatic cytochrome P 450 enzymes by means of EROD (ethoxyresorufin-O-deethylase) assays in human, rat, chick, and rainbow trout cells. Both pure PBDE congeners and com. PBDE mixtures had Ah receptor binding affinities 10^-2-10^-5 times that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast with polychlorinated biphenyls, Ah receptor binding affinities of PBDEs could not be related to the planarity of the mol., possibly because the large size of the bromine atoms expands the Ah receptor’s binding site. EROD activities of the PBDE congeners followed a similar rank order in all cells. Some congeners, notably PBDE 85, did not follow the usual trend in which strength of Ah receptor binding affinity paralleled P 450 induction potency. Use of the gel retardation assay with a synthetic oligonucleotide indicated that in these cases the liganded Ah receptor failed to bind to the DNA recognition sequence. In the experiment, the researchers used many compounds, for example, 3,4-Dibromoaniline (cas: 615-55-4Application of 615-55-4).

3,4-Dibromoaniline (cas: 615-55-4) 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. 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.Application of 615-55-4

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Prediction of Kinetic Isotope Effects for Various Hydride Transfer Reactions Using a New Kinetic Model was written by Shen, Guang-Bin;Xia, Ke;Li, Xiu-Tao;Li, Jun-Ling;Fu, Yan-Hua;Yuan, Lin;Zhu, Xiao-Qing. And the article was included in Journal of Physical Chemistry A in 2016.Application In Synthesis of 3,4-Dibromoaniline This article mentions the following:

In this work, kinetic isotope effect (KIE_self) values of 68 hydride self-exchange reactions, XH(D) + X⁺ â†?X⁺ + XH(D), in acetonitrile at 298 K were determined using a new exptl. method. KIE values of 4556 hydride cross transfer reactions, XH(D) + Y⁺ â†?X⁺ + YH(D), in acetonitrile were estimated from the 68 determined KIE_self values of hydride self-exchange reactions using a new KIE relation formula derived from Zhu’s kinetic equation and the reliability of the estimations was verified using different exptl. methods. A new KIE kinetic model to explain and predict KIE values was developed according to Zhu’s kinetic model using two different Morse free energy curves instead of one Morse free energy curve in the traditional KIE theories to describe the free energy changes of X-H bond and X-D bond dissociation in chem. reactions. The most significant contribution of this paper to KIE theory is to build a new KIE kinetic model, which can be used to not only uniformly explain the various (normal, enormous and inverse) KIE values but also safely predict KIE values of various chem. reactions. In the experiment, the researchers used many compounds, for example, 3,4-Dibromoaniline (cas: 615-55-4Application In Synthesis of 3,4-Dibromoaniline).

3,4-Dibromoaniline (cas: 615-55-4) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. 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.Application In Synthesis of 3,4-Dibromoaniline

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Total Synthesis of Dictyodendrins A-E was written by Tokuyama, Hidetoshi;Okano, Kentaro;Fujiwara, Hideto;Noji, Toshiharu;Fukuyama, Tohru. And the article was included in Chemistry – An Asian Journal in 2011.Electric Literature of C9H11BrO This article mentions the following:

A highly efficient total synthesis of dictyodendrins A-E was accomplished. The synthesis features a novel benzyne-mediated one-pot indoline formation/cross-coupling sequence for the construction of a highly substituted key indoline intermediate. Peripheral substituents were introduced onto this intermediate in a modular fashion to complete the total synthesis of dictyodendrins A-E. 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. 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. 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.Electric Literature of C9H11BrO

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

New enantiomeric fluorine-containing derivatives of sulforaphane: Synthesis, absolute configurations and biological activity was written by Kielbasinski, Piotr;Luczak, Jerzy;Cierpial, Tomasz;Blaszczyk, Jaroslaw;Sieron, Leslaw;Wiktorska, Katarzyna;Lubelska, Katarzyna;Milczarek, Malgorzata;Chilmonczyk, Zdzislaw. And the article was included in European Journal of Medicinal Chemistry in 2014.Name: N-(5-Bromopentyl)phthalimide This article mentions the following:

Three pairs of enantiomers of the unknown sulforaphane analogs, e.g. CF₃S(O)(CH₂)₄NCS, bearing organofluorine substituents bonded to the sulfinyl sulfur atom and having different number of methylene groups in the central carbon chain were synthesized and fully characterized, including determination of their absolute configurations. All the new compounds were tested in vitro for their cytotoxicity against melanoma cells to show increased activity in comparison with the natural sulforaphane. The influence of the particular structural changes in the mol. on the cytotoxicity is discussed. In the experiment, the researchers used many compounds, for example, N-(5-Bromopentyl)phthalimide (cas: 954-81-4Name: N-(5-Bromopentyl)phthalimide).

N-(5-Bromopentyl)phthalimide (cas: 954-81-4) 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. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Name: N-(5-Bromopentyl)phthalimide

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Structure-Activity Relationship Studies of Indole-Based Compounds as Small Molecule HIV-1 Fusion Inhibitors Targeting Glycoprotein 41 was written by Zhou, Guangyan;Sofiyev, Vladimir;Kaur, Hardeep;Snyder, Beth A.;Mankowski, Marie K.;Hogan, Priscilla A.;Ptak, Roger G.;Gochin, Miriam. And the article was included in Journal of Medicinal Chemistry in 2014.Related Products of 6515-58-8 This article mentions the following:

We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure-activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and mol. properties. Thirty new compounds were evaluated in binding, cell-cell fusion, and viral replication assays. Below a 1 μM threshold, correlation between binding and biol. activity was diminished, indicating an amphipathic requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 μM binding affinity and 0.2 μM EC₅₀ against cell-cell fusion and live virus replication and was active against T20 resistant strains. Twenty-two compounds with the same connectivity displayed a consensus pose in docking calculations, with rank order matching the biol. activity. The work provides insight into requirements for small mol. inhibition of HIV-1 fusion and demonstrates a potent low mol. weight fusion inhibitor. In the experiment, the researchers used many compounds, for example, 3-(Bromomethyl)benzoic acid (cas: 6515-58-8Related Products of 6515-58-8).

3-(Bromomethyl)benzoic acid (cas: 6515-58-8) 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 principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Related Products of 6515-58-8

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines was written by Hunt, Thomas;Atherton-Watson, Hazel C.;Axford, Jake;Collingwood, Stephen P.;Coote, Kevin J.;Cox, Brian;Czarnecki, Sarah;Danahay, Henry;Devereux, Nick;Howsham, Catherine;Hunt, Peter;Paddock, Victoria;Paisley, Derek;Young, Alice. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.SDS of cas: 954-81-4 This article mentions the following:

We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC₅₀ of 200 nM and is efficacious in the Guinea-pig tracheal p.d. (TPD) model of ENaC blockade with an ED₅₀ of 44 μg kg^-1 at 1 h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers. In the experiment, the researchers used many compounds, for example, N-(5-Bromopentyl)phthalimide (cas: 954-81-4SDS of cas: 954-81-4).

N-(5-Bromopentyl)phthalimide (cas: 954-81-4) 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. 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.SDS of cas: 954-81-4

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Discovery of 2-arylamino-4-(1-methyl-3-isopropylsulfonyl-4-pyrazol-amino)pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors was written by Zhang, Peilong;Dong, Jiaqiang;Zhong, Boyu;Zhang, Deyi;Jin, Can;Meng, Xuejing;Sun, Desheng;Xu, Xiangyuan;Zhou, Yong;Liang, Zhi;Ji, Minghua;Li, Hailong;Xu, Tao;Song, Guowei;Zhang, Ling;Chen, Gang;Yuan, Hongbin;Shih, Joe;Zhang, Ruihao;Hou, Guojun;Jin, Ying;Yang, Qiong. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2015.Related Products of 95668-20-5 This article mentions the following:

A new series of 2,4-diamino pyrimidine derivatives with a sulfone-substituted pyrazole right side-chain were discovered as potent anaplastic lymphoma kinase inhibitors. Structure-activity relationship of the left side-chain on Ph substitutions were explored which delivered many potent ALK inhibitors. Among them, I showed favorable pharmacokinetic profiles in rats and dogs together with significant antitumor efficacy in EML4-ALK fusion xenograft model. In the experiment, the researchers used many compounds, for example, 3-Nitro-4-(trifluoromethoxy)bromobenzene (cas: 95668-20-5Related Products of 95668-20-5).

3-Nitro-4-(trifluoromethoxy)bromobenzene (cas: 95668-20-5) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. 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.Related Products of 95668-20-5

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Molecular photoswitches based on spiro-acridans was written by Raskosova, Alina;Stoesser, Reinhard;Abraham, Werner. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2013.Application In Synthesis of Ethyl (2-bromophenyl)acetate This article mentions the following:

Thermally reversible photochromic spiro-acridans have been synthesized for the first time. They exhibit high ring opening efficiencies. As the formed zwitterions do not possess a merocyanine structure their lifetime is in the range of milliseconds to seconds. An observed side reaction can be avoided by suitable substitution of hydrogen atoms. In the experiment, the researchers used many compounds, for example, Ethyl (2-bromophenyl)acetate (cas: 2178-24-7Application In Synthesis of Ethyl (2-bromophenyl)acetate).

Ethyl (2-bromophenyl)acetate (cas: 2178-24-7) 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 principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Application In Synthesis of Ethyl (2-bromophenyl)acetate

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary