Month: February 2023

A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor was written by Griffith, David A.;Edmonds, David J.;Fortin, Jean-Philippe;Kalgutkar, Amit S.;Kuzmiski, J. Brent;Loria, Paula M.;Saxena, Aditi R.;Bagley, Scott W.;Buckeridge, Clare;Curto, John M.;Derksen, David R.;Dias, Joao M.;Griffor, Matthew C.;Han, Seungil;Jackson, V. Margaret;Landis, Margaret S.;Lettiere, Daniel;Limberakis, Chris;Liu, Yuhang;Mathiowetz, Alan M.;Patel, Jayesh C.;Piotrowski, David W.;Price, David A.;Ruggeri, Roger B.;Tess, David A.. And the article was included in Journal of Medicinal Chemistry in 2022.Recommanded Product: 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde This article mentions the following:

Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have revolutionized diabetes therapy, but their use has been limited because they require injection. Herein, we describe the discovery of the orally bioavailable, small-mol., GLP-1R agonist PF-06882961 (danuglipron). A sensitized high-throughput screen was used to identify 5-fluoropyrimidine-based GLP-1R agonists that were optimized to promote endogenous GLP-1R signaling with nanomolar potency. Incorporation of a carboxylic acid moiety provided considerable GLP-1R potency gains with improved off-target pharmacol. and reduced metabolic clearance, ultimately resulting in the identification of danuglipron. Danuglipron increased insulin levels in primates but not rodents, which was explained by receptor mutagenesis studies and a cryogenic electron microscope structure that revealed a binding pocket requiring a primate-specific tryptophan 33 residue. Oral administration of danuglipron to healthy humans produced dose-proportional increases in systemic exposure (NCT03309241). This opens an opportunity for oral small-mol. therapies that target the well-validated GLP-1R for metabolic health. In the experiment, the researchers used many compounds, for example, 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4Recommanded Product: 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde).

1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4) belongs to imidazole derivatives. The solubility of imidazoles in ethers is lower than that in alcohols and decreases with increasing chain length of the ethers . In contrast, the solubility of benzimidazoles in alcohols (C3鈥揅6) is higher than in water and generally decreases with a This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Recommanded Product: 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Investigation on the Coordination Mode of IL-Supported Diols Used as Phosphine-Free Ligands for Palladium Catalyzed Heck Reaction was written by Cai, Yueqin;Song, Gonghua;Chen, Xiao. And the article was included in Chinese Journal of Chemistry in 2013.COA of Formula: C11H20N2 This article mentions the following:

The coordination mode of IL-supported diols used as phosphine-free ligands for palladium catalyzed Heck reaction was investigated by tuning their compositions The difference in coordination of these IL-supported diols with metal Pd in Heck reaction was related to the changes of the cation rings, leading to the different activities of Pd catalyst in the reaction. The exptl. results indicated that the activities of Pd catalyst were affected mainly by 蟺-electron d. of the cation rings. Compared to pyridinium and piperidinium cations, imidazolium cations showed the best coordination to metal Pd. In the meantime, C-2 hydrogen and the length of alkyl side chains had impacts on the coordination as well. In the experiment, the researchers used many compounds, for example, 1-Octyl-1H-imidazole (cas: 21252-69-7COA of Formula: C11H20N2).

1-Octyl-1H-imidazole (cas: 21252-69-7) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.COA of Formula: C11H20N2

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

2-Pyridyl P1′-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors (A-792611 and A-790742) with Potential for Convenient Dosing and Reduced Side Effects was written by De Goey, David A.;Grampovnik, David J.;Flentge, Charles A.;Flosi, William J.;Chen, Hui-ju;Yeung, Clinton M.;Randolph, John T.;Klein, Larry L.;Dekhtyar, Tatyana;Colletti, Lynn;Marsh, Kennan C.;Stoll, Vincent;Mamo, Mulugeta;Morfitt, David C.;Nguyen, Bach;Schmidt, James M.;Swanson, Sue J.;Mo, Hongmei;Kati, Warren M.;Molla, Akhteruzzaman;Kempf, Dale J.. And the article was included in Journal of Medicinal Chemistry in 2009.COA of Formula: C9H8N2O This article mentions the following:

A series of symmetry-based HIV protease inhibitors I (R¹ = 2-FC₆H₄, 3-MeC₆H₄, 2-H₂NC₆H₄, 6-methyl-2-pyridyl, 4-quinazolyl, 2-methyl-4-thiazolyl, 1-methyl-2-benzimidazolyl, etc.; R² = OH, R³ = H; R² = H, R³ = OH) was designed and synthesized. Modification of the core regiochem. and stereochem. significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendant arylmethyl P3 group. Optimization led to the selection of two compounds, (R)-I [R¹ = 6-(2-hydroxypropan-2-yl)-2-pyridyl; R² = OH; R³ = H] (A-790742) and (S)-I (R¹ = Ph; R² = OH; R³ = H) (A-792611), for advancement to preclin. studies. Both compounds displayed low nanomolar potency against wild type HIV in the presence of human serum, low rates of metabolism in human liver microsomes, and high oral bioavailability in animal models. The compounds were examined in a preclin. model for the hyperbilirubinemia observed with some HIV PIs, and both exhibited less bilirubin elevation than comparator compounds X-ray crystallog. analyses of the new cores were used to examine differences in their binding modes. The antiviral activity of the compounds against protease inhibitor resistant strains of HIV was also determined In the experiment, the researchers used many compounds, for example, 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4COA of Formula: C9H8N2O).

1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.COA of Formula: C9H8N2O

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Identification of parallel medicinal chemistry protocols to expand branched amine design space was written by Conn, Edward L.;Perry, Matthew A.;Shi, Kecheng;Wang, Guotao;Hoy, Susan;Sach, Neal W.;Qi, Wenying;Qu, Liqiang;Gao, Yu;Xu, Yan;Schmitt, Daniel C.. And the article was included in Organic & Biomolecular Chemistry in 2022.Product Details of 25676-75-9 This article mentions the following:

Methods for the synthesis of 伪-branched heteroaryl amines RCH(R¹)NH(R²) (R = tert-Bu, Ph, 1-methyl-1H-imidazol-4-yl, pyridin-2-yl, etc. R¹ = 1-methyl-1H-pyrazol-5-yl, pyridin-3-yl, 1-propyl-1H-pyrazol-4-yl, 4-bromo-2-hydroxyphenyl, etc.; R² = pyridin-2-yl, Ph, 4-phenylpyridin-2-yl, pyrazin-2-yl, etc.) via aldimine addition have been evaluated for compatibility with parallel synthesis. In situ activation of aliphatic carboxylic acids RC(O)OH as redox-active esters enables Zn-mediated decarboxylative radical imine R¹CH=NR² addition to access aliphatic-branched heterobenzylic amines. In situ activation of (hetero)aryl bromides RBr via Li-halogen exchange enables heteroaryl-lithium addition to imines to access (hetero)benzhydryl amines. Condensation of heteroaryl amines RNH₂ with heteroaryl aldehydes R¹CHO provides aldimines which may be intercepted with aryl Grignard reagents to provide modular access to (hetero)benzhydryl amines. These protocols minimize synthetic step count and maximize accessible design space, enhancing access to 伪-branched heteroaryl amines for medicinal chem. In the experiment, the researchers used many compounds, for example, 4-Bromo-1-methylimidazole (cas: 25676-75-9Product Details of 25676-75-9).

4-Bromo-1-methylimidazole (cas: 25676-75-9) belongs to imidazole derivatives. The solubility of imidazoles in ethers is lower than that in alcohols and decreases with increasing chain length of the ethers . In contrast, the solubility of benzimidazoles in alcohols (C3鈥揅6) is higher than in water and generally decreases with a Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.Product Details of 25676-75-9

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

BODIPY-BODIPY dyad: assessing the potential as a viscometer for molecular and ionic liquids was written by Kimball, Joseph D.;Raut, Sangram;Jameson, Laramie P.;Smith, Nicholas W.;Gryczynski, Zygmunt;Dzyuba, Sergei V.. And the article was included in RSC Advances in 2015.Product Details of 404001-48-5 This article mentions the following:

A sym. BODIPY-BODIPY dyad with a diyne linker was prepared in two steps; the lifetime decay of this rotor appeared to correlate with the viscosity of the media, thus making this dyad a suitable small mol. viscometer for mol. solvents. The potential of using the rotor to probe the viscosity of ionic liquids was also investigated. In the experiment, the researchers used many compounds, for example, 3-Dodecyl-1-methyl-1H-imidazol-3-ium bis((trifluoromethyl)sulfonyl)amide (cas: 404001-48-5Product Details of 404001-48-5).

3-Dodecyl-1-methyl-1H-imidazol-3-ium bis((trifluoromethyl)sulfonyl)amide (cas: 404001-48-5) belongs to imidazole derivatives. 1H-imidazole is an imidazole tautomer which has the migrating hydrogen at position 1. It is a conjugate base of an imidazolium cation. It is a conjugate acid of an imidazolide. It is a tautomer of a 4H-imidazole. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.Product Details of 404001-48-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Dehydration of glucose and fructose into 5-hydroxymethylfurfural catalyzed by Lewis acid in ionic liquids was written by Tian, Yukui;Deng, Jin;Pan, Tao;Guo, Qingxiang;Fu, Yao. And the article was included in Cuihua Xuebao in 2011.Application of 79917-89-8 This article mentions the following:

A variety of Lewis acids have been examined for the transformation of glucose and fructose into 5-hydroxymethylfurfural (5-HMF) in ionic liquids (ILs). SnCl_n, and CrCl_n are effective catalysts for the isomerization, and Lewis acids with strong acidity can facilitate the dehydration of fructose. The influence of ILs structure, including the length of alkyl side chain and halide anions, on the conversion was also studied. A distinct odd-even carbon-atom-number effect is observed in the conversion of glucose to 5-HMF and the imidazolium bromides with short alkyl side-chains can provide a higher yield of 5-HMF from fructose. In the presence of 1-ethyl-3-methylimidazolium bromide ([C₂MIM]Br) and SnCl₂, the yields of 5-HMF are 65% and 73% from glucose and fructose, resp. In the experiment, the researchers used many compounds, for example, 1-Methyl-3-propylimidazolium Chloride (cas: 79917-89-8Application of 79917-89-8).

1-Methyl-3-propylimidazolium Chloride (cas: 79917-89-8) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Application of 79917-89-8

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

An efficient ICT based fluorescent turn-on dyad for selective detection of fluoride and carbon dioxide was written by Ali, Rashid;Razi, Syed S.;Gupta, Ramesh C.;Dwivedi, Sushil K.;Misra, Arvind. And the article was included in New Journal of Chemistry in 2016.Name: 4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid This article mentions the following:

A new intramol. charge transfer (ICT) based fluorescent turn-on ratiometric probe 2 (D-蟺-A type) has been designed and synthesized by bridging imidazole (donor, D) and benzothiazole (acceptor, A) moieties through a Ph ring. The photophys. behavior of probe 2 in solvents of different polarities and at different pH values has been investigated. Upon interaction with different types of anions probe 2 showed selective high affinity for fluoride anions (F^–) in aqueous DMSO (20%) solution The ratiometric fluorescence turn-on behavior displayed by 2 with F^– is attributed to changes in the ICT process. Job’s plot anal. revealed a 1 : 1 binding stoichiometry for 2 + F^– interactions with a high binding constant and detection sensitivity (30 ppb). Moreover, a solution of 2 + F^– enabled the detection of CO₂ (鈭?00 ppb; 2.29 渭M) through enhanced emission. The mode of interaction has been confirmed by ¹H NMR titration studies which suggested the deprotonation of the -NH fragment of an imidazolyl unit in the presence of F^–. In the experiment, the researchers used many compounds, for example, 4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid (cas: 5496-35-5Name: 4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid).

4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid (cas: 5496-35-5) belongs to imidazole derivatives. Imidazole derivatives generally have good solubility in protic solvents. Simple imidazole derivatives, such as 1H-imidazole, 2-methyl-1H-imidazole, and 1,2-dimethylimidazole, have very high solubility in water. Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.Name: 4-(4,5-Diphenyl-1H-imidazol-2-yl)benzoic acid

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Photoisomerization of indazoles to benzimidazoles was written by Tiefenthaler, H.;Dorscheln, W.;Goth, H.;Schmid, H.. And the article was included in Tetrahedron Letters in 1964.SDS of cas: 4887-83-6 This article mentions the following:

Indazole, 3-, 4-, 5-, 6-, or 7-methyl-, and 6-methoxyindazole irradiated with uv light (high pressure Hg lamp) in MeOH, EtOAc, or dioxane 3-20 hrs. at 25-90掳 were irreversibly converted in 9-31% yields to the corresponding benzimidazoles. The influence of solvent, reaction time, and temperature was tabulated. No isomerization was noted for 3-Ph-, 5-MeO-, 5-Cl-, and 6-Cl-substituted imidazoles. Pyrazole on irradiation in dioxane gave 12% imidazole. In the experiment, the researchers used many compounds, for example, 7-Methyl-1H-benzo[d]imidazole (cas: 4887-83-6SDS of cas: 4887-83-6).

7-Methyl-1H-benzo[d]imidazole (cas: 4887-83-6) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.SDS of cas: 4887-83-6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-喂 was written by Sajan, Mini P.;Nimal, Sonali;Mastorides, Stephen;Acevedo-Duncan, Mildred;Kahn, C. Ronald;Fields, Alan P.;Braun, Ursula;Leitges, Michael;Farese, Robert V.. And the article was included in Metabolism, Clinical and Experimental in 2012.HPLC of Formula: 26832-08-6 This article mentions the following:

Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly reversed or markedly improved most if not all metabolic abnormalities. Here, we examined effects of 2 newly developed small-mol. PKC-喂/位 inhibitors. We used the mouse model of heterozygous muscle-specific knockout of PKC-位, in which partial deficiency of muscle PKC-位 impairs glucose transport in muscle and thereby causes glucose intolerance and hyperinsulinemia, which, via hepatic aPKC activation, leads to abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. One inhibitor, 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)]], binds to the substrate-binding site of PKC-位/喂, but not other PKCs. The other inhibitor, aurothiomalate, binds to cysteine residues in the PB1-binding domains of aPKC-位/喂/味 and inhibits scaffolding. Treatment with either inhibitor for 7 days inhibited aPKC, but not Akt, in liver and concomitantly improved insulin signaling to Akt and aPKC in muscle and adipocytes. Moreover, both inhibitors diminished excessive expression of hepatic, aPKC-dependent lipogenic, proinflammatory, and gluconeogenic factors; and this was accompanied by reversal or marked improvements in hyperglycemia, hyperinsulinemia, abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. Our findings highlight the pathogenetic importance of insulin signaling to hepatic PKC-喂 in obesity, the metabolic syndrome, and type 2 diabetes mellitus and suggest that 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)]] and aurothiomalate or similar agents that selectively inhibit hepatic aPKC may be useful treatments. In the experiment, the researchers used many compounds, for example, 1H-Imidazole-4-carboxamide (cas: 26832-08-6HPLC of Formula: 26832-08-6).

1H-Imidazole-4-carboxamide (cas: 26832-08-6) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.HPLC of Formula: 26832-08-6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ionic liquid-functionalized crystals of barium sulfate: A hybrid organic-inorganic material with tuned hydrophilicity and solid-liquid behavior was written by Kowacz, Magdalena;Marchel, Mateusz;Esperanca, Jose M. S. S.;Rebelo, Luis Paulo N.. And the article was included in Materials Chemistry and Physics in 2015.HPLC of Formula: 404001-48-5 This article mentions the following:

A hybrid organic-inorganic material composed of barium sulfate (BaSO₄) crystals embedded within a hydrophobic ionic liquid (ILs) matrix was synthesized. The contact between the inorganic solid and the organic coating is created by chem. interactions between the crystal surface and the ionic liquid The material exhibits higher affinity to lipophilic media than the nonmodified BaSO₄. Increased hydrophobicity is a property often sought for inorganic particles to be applied in nonpolar formulations. Immobilization of water-immiscible ILs on a hydrophilic solid carrier enables their application in aqueous solutions and the creation of appreciable hydrophobic-IL/water interfaces on the dispersion of solid-like material in aqueous media. In the experiment, the researchers used many compounds, for example, 3-Dodecyl-1-methyl-1H-imidazol-3-ium bis((trifluoromethyl)sulfonyl)amide (cas: 404001-48-5HPLC of Formula: 404001-48-5).

3-Dodecyl-1-methyl-1H-imidazol-3-ium bis((trifluoromethyl)sulfonyl)amide (cas: 404001-48-5) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.HPLC of Formula: 404001-48-5

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem