Month: February 2023

Nitroimidazole-based ‘extruded mustards’ designed as reductively activated hypoxia-selective cytotoxins was written by Hay, Michael P.;Denny, William A.;Wilson, William R.. And the article was included in Anti-Cancer Drug Design in 1996.Synthetic Route of C5H5N3O4 This article mentions the following:

A new class of nitroimidazole alkanoic acid amides, designed to extrude para-aminophenyl mustard by intramol. cyclization following reduction of the nitro group, have been prepared and evaluated for their ability to function as bioreductively activated prodrugs. The mechanism of activation following (bio)reduction was studied using the model compounds and the related mustard analogs. However, the reduced forms of these compounds were relatively stable and not susceptible to intramol. cyclization. This is in contrast to the corresponding 2-nitrophenylalkyl amides, where the hydroxylamino or amino reduction products undergo intramol. cyclization via a tetrahedral intermediate, resulting in cleavage of the amide and release of an activated aromatic mustard. One of the 2-nitroimidazole mustards (I) had 20-fold greater toxicity towards aerobic AA8 cells than RB 6145, and a 51-fold greater toxicity towards UV4 cells (which are defective in DNA cross-link repair and thus hypersensitive to crosslinking agents). The cytotoxicity of I against AA8 cells was enhanced 3.3-fold under hypoxic conditions, but the compound was inactive against the hypoxic subfraction of cells in KHT tumors in vivo. In the experiment, the researchers used many compounds, for example, 2-(2-Nitro-1H-imidazol-1-yl)acetic acid (cas: 22813-32-7Synthetic Route of C5H5N3O4).

2-(2-Nitro-1H-imidazol-1-yl)acetic acid (cas: 22813-32-7) 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. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Synthetic Route of C5H5N3O4

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Connection between dielectric constant and total number of hydrogen-bond groups per cation-anion pair in ionic liquids was written by Shi, Baoli. And the article was included in Journal of Molecular Liquids in 2020.Application of 35487-17-3 This article mentions the following:

This paper reports a quant. connection between the dielec. constant and calculated total number of hydrogen-bond groups per cation-anion pair for 44 ionic liquids, including 15 ionic liquids with high dielec. constants exceeding 20. The total number of hydrogen-bond groups per cation-anion pair was equal to the addition of the hydrogen-bond group number per cation and per anion. The methylene group could reduce the group number capable of forming hydrogen bonds, and one methylene group caused a decrease of 1 hydrogen-bond number Regardless of whether a liquid was ionic or non-ionic liquid, approx. linear relationship were observed between dielec. constant and total hydrogen-bond number per mol. For ionic liquids, an increase of 1 in the total number of hydrogen-bond groups per cation-anion pair resulted in an increase of approx. 8.5 in the dielec. constant For non-ionic liquids, the value was approx. 21.9. The average molar d. of nine hydrogen-bonded ionic liquids with high dielec. constants was 9.3 x 10³ mol/m³, while the average molar d. of eight non-ionic liquids with hydrogen-bonds was 21.1 x 10³ mol/m³. The 21.1 M d. coefficient of the non-ionic liquids was almost equal to the 21.9 coefficient in the dielec. constant equation, and the 9.3 M d. coefficient of the ionic liquids was very close to the 8.5 coefficient in its dielec. constant equation. This result indicated that the effect mechanisms of the intermol. hydrogen-bond structure on dielec. constant were similar for the two types of liquids In the experiment, the researchers used many compounds, for example, 1-Methyl-1H-imidazol-3-ium chloride (cas: 35487-17-3Application of 35487-17-3).

1-Methyl-1H-imidazol-3-ium chloride (cas: 35487-17-3) belongs to imidazole derivatives. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The pharmacophore of imidazole exists in bioactive compounds including amino acids, plant growth regulators and therapeutic agents.n increase of the alkyl chain length of the alcohols. Application of 35487-17-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

N-Heterocyclic Carbene (NHC)-Stabilized Ru⁰ Nanoparticles: In Situ Generation of an Efficient Transfer Hydrogenation Catalyst was written by Kathuria, Lakshay;Din Reshi, Noor U.;Samuelson, Ashoka G.. And the article was included in Chemistry – A European Journal in 2020.Related Products of 1632-83-3 This article mentions the following:

Tethered and untethered ruthenium half-sandwich complexes I [R = 2,4,6-(CH₃)₃, 4-i-Pr, H, 3-Me, etc.; n = 1, 2] and II were synthesized and characterized spectroscopically. X-ray crystallog. anal. of three untethered I (n = 1, R = 3-OMe; n = 1, R = 4-i-Pr; n = 1, R = 4-NO₂) and two tethered Ru N-heterocyclic carbene (NHC) complexes II (R = 3-OMe, 2,4,6-(CH₃)₃) were also carried out. These RuNHC complexes catalyze transfer hydrogenation of aromatic ketones as acetophenone, 2,3-dihydro-1H-inden-1-one, 1-(furan-2-yl)ethan-1-one, etc. in 2-propanol under reflux, optimally in the presence of (25 mol%) KOH. Under these conditions, the formation of 2-3 nm-sized Ru0 nanoparticles was detected by TEM measurements. A solid-state NMR investigation of the nanoparticles suggested that the NHC ligands were bound to the surface of the Ru nanoparticles (NPs). This base-promoted route to NHC-stabilized ruthenium nanoparticles directly from arene-tethered ruthenium-NHC complexes and from untethered ruthenium-NHC complexes is more convenient than previously known routes to NHC-stabilized Ru nanocatalysts. Similar catalytically active RuNPs were also generated from the reaction of a mixture of [RuCl₂(p-cymene)]₂ and the NHC precursor with KOH in isopropanol under reflux. The transfer hydrogenation catalyzed by these NHC-stabilized RuNPs possess a high turnover number The catalytic efficiency was significantly reduced if nanoparticles were exposed to air or allowed to aggregate and precipitate by cooling the reaction mixtures during the reaction. In the experiment, the researchers used many compounds, for example, 1-Methylbenzimidazole (cas: 1632-83-3Related Products of 1632-83-3).

1-Methylbenzimidazole (cas: 1632-83-3) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Related Products of 1632-83-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Estimation of the solubility with cosolvent composition by combinated of the Williams-Amidon model with quasi virial coefficient was written by Wang, Haiyang;Zhang, Xinwei. And the article was included in Asia-Pacific Journal of Chemical Engineering in 2020.Synthetic Route of C33H34N6O6 This article mentions the following:

A new model that combined the Williams-Amidon model with quasi virial coefficient (WA-QVC) was proposed. Compared with the log-linear model, the modified Wilson model, and the Williams-Amidon model, the WA-QVC model has the highest accuracy to correlate the solubility for cosolvent composition, R²>0.999. For lutelin, it can be seen that the order of R² was WA-QVC>WA>MW>L-L, while the order of root-mean-square deviation was WA-QVC<WA<MW<L-L. Subsequently, the phys. meaning of several model parameters of B₁, X₁, B₂, B₃, and α were discussed and described by the Apelblat model, the exponential model, and the quadratic equation. In addition, the WA-QVC model was tested and verified by solubility data of different solutes in different mixture with higher accuracy, indicating that the WA-QVC model has great application prospect. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Synthetic Route of C33H34N6O6).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.Synthetic Route of C33H34N6O6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Regioselectivity in the Cu(I)-Catalyzed [4 + 2]-Cycloaddition of 2-Nitrosopyridine with Unsymmetrical Dienes was written by Tran, Anh T.;Liu, Peng;Houk, K. N.;Nicholas, Kenneth M.. And the article was included in Journal of Organic Chemistry in 2014.Synthetic Route of C9H8N2O This article mentions the following:

The thermal (uncatalyzed) and Cu(I)-catalyzed reactions of 2-nitrosopyridine (PyrNO) with the dienes 1,3-pentadiene, E,E-2,4-hexadienol, and 1-phenylbutadiene are studied exptl. and computationally. The uncatalyzed reactions of the first two dienes occur with low regioselectivity, while the latter proceeds with complete proximal selectivity. Using the M06/6-311+G(d,p)-SDD method, various concerted transition states for the reactions of 2-nitrosopyridine with (E)-1,3-pentadiene and 1-phenylbutadiene were computed. In quant. agreement with the exptl. findings, (a) no energy difference (0.0 kcal/mol) is found between the most stable transition states, endo-prox-anti and endo-dist-anti, in the pentadiene/PyrNO reaction, leading to nearly equal amounts of prox and dist cycloadducts, and (b) the proximal transition state is strongly favored (by 3.7 kcal/mol) over the distal for the highly selective phenylbutadiene/PyrNO reaction. The regioselectivity of the pentadiene/PyrNO reaction is improved markedly (90:10 dist/prox) when catalyzed by Cu(CH₃CN)₄⁺; (diimine)₂Cu⁺ catalysts increase selectivity for the proximal product (55-65%). Modest effects of the catalyst nature on regioselectivity are observed in the sorbyl alc. and 1-phenylbutadiene reactions. The relative affinity of an equilibrating set of (diimine)₂Cu⁺ complexes for the prox and dist cycloadducts, assessed by ESI-MS, is marginally correlated with the prox/dist product regioselectivity produced by the corresponding catalysts. Transition states in the Cu(CH₃CN)₄⁺– and Cu(diimine)₂⁺-catalyzed reactions are located that account for the observed regioselectivities. Coordination effects on the regioselectivity are derived from FMO orbital interactions and the extent of electron transfer between the Cu center and the coordinated nitroso and diene units. In the experiment, the researchers used many compounds, for example, 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4Synthetic Route of C9H8N2O).

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–C6) is higher than in water and generally decreases with a 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.Synthetic Route of C9H8N2O

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Design of Benzimidazolyl Phosphines Bearing Alterable P,O or P,N-Coordination: Synthesis, Characterization, and Insights into Their Reactivity was written by Wong, Shun Man;Choy, Pui Ying;Zhao, Qingyang;Yuen, On Ying;Yeung, Chung Chiu;So, Chau Ming;Kwong, Fuk Yee. And the article was included in Organometallics in 2021.Name: 1-Methylbenzimidazole This article mentions the following:

A new series of hemilabile benzimidazolyl phosphines is reported. Entities in this ligand family can be easily assembled and prepared on a large scale via a simple one-pot procedure. X-ray crystallog. analyses show that the Pd metal center can coordinate in different fashions, where it relies on the size of the -PR₂ group. With the same ligand scaffold, the ligand having a -PCy₂ moiety displays better efficiency in expediting aromatic C-C bond-coupling reactions, while the ligand associated with a -P^tBu₂ group, in contrast, promotes C-N bond-forming reactions. In the experiment, the researchers used many compounds, for example, 1-Methylbenzimidazole (cas: 1632-83-3Name: 1-Methylbenzimidazole).

1-Methylbenzimidazole (cas: 1632-83-3) 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.Name: 1-Methylbenzimidazole

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Enantioselective Synthesis of Multisubstituted Spirocyclopentane Oxindoles Enabled by Pd/Chiral Rh(III) Complex Synergistic Catalysis was written by Wan, Qian;Chen, Liang;Li, Shiwu;Kang, Qiang;Yuan, Yaofeng;Du, Yu. And the article was included in Organic Letters in 2020.Formula: C6H8N2O This article mentions the following:

An asym. [3 + 2]-cycloaddition reaction of α,β-unsaturated 2-acyl imidazoles with spirovinylcyclopropanyl-2-oxindoles catalyzed synergistically by an achiral palladium(0) catalyst and a chiral-at-metal rhodium(III) complex has been developed. A series of biol. important 3-spirocyclopentane-2-oxindoles with four contiguous stereocenters were synthesized in high yields (up to 99%) with excellent stereoselectivities (up to 99% ee, 20:1 dr). In the experiment, the researchers used many compounds, for example, 1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1Formula: C6H8N2O).

1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1) 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.Formula: C6H8N2O

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Controlling a Cohort: Use of Mirabilis-Based Purge Calculations to Understand Nitrosamine-Related Risk and Control Strategy Options was written by Burns, Michael J.;Teasdale, Andrew;Elliott, Eric;Barber, Chris G.. And the article was included in Organic Process Research & Development in 2020.Application In Synthesis of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate This article mentions the following:

The recent discovery of nitrosamines within marketed drugs, such as Valsartan, has led to changes within the regulatory landscape. Most notably, the requirement for a risk evaluation of the presence of nitrosamines within the drug product has been extended from sartan-type tetrazole containing drugs to all marketed products. The largest inherent risks associated with a drug substance will generally arise from impurity formation and carryover in the synthetic manufacturing process. Despite the classification of nitrosamines within the cohort of concern, the understanding of their behavior based on physicochem. properties is unaffected by this status, and as such all control options laid out in ICH M7 should be considered acceptable. This communication aims to show how the use of purge calculations, utilizing the Mirabilis software, fully de-risked nitrosamine concerns related to the development of Candesartan cilexetil. Aligned to the principles of impurity control in the ICH M7 guideline, this provided a suitable strategy to determine, and subsequently demonstrate control of, the nitrosamine risk. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Application In Synthesis of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate).

1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) 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. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Application In Synthesis of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Discovery of Isoindoline Amide Derivatives as Potent and Orally Bioavailable ADAMTS-4/5 Inhibitors for the Treatment of Osteoarthritis was written by Zhao, Peng;Liu, Dong;Song, Chunying;Li, Di;Zhang, Xinzhu;Horecny, Ivana;Zhang, Fengqi;Yan, Yuna;Zhuang, Linghang;Li, Jing;Liu, Suxing;Mao, Yuchang;Feng, Jun;Liu, Jian;Tao, Weikang. And the article was included in ACS Pharmacology & Translational Science in 2022.Application of 85692-37-1 This article mentions the following:

Osteoarthritis (OA) treatment is a highly unmet medical need. Development of a disease-modifying OA drug (DMOAD) is challenging with no approved drugs on the market. Inhibition of ADATMS-4/5 is a promising OA therapeutics to target cartilage degradation and potentially can reduce joint pain and restore its normal function. Starting from the reported ADAMTS-5 inhibitor GLPG1972, we applied a scaffold hopping strategy to generate a novel isoindoline amide scaffold. Representative compound I showed high potency in ADATMS-4/5 inhibition, as well as good selectivity over a panel of other metalloproteases. In addition, compound I exhibited excellent druglike properties and showed better pharmacokinetic (PK) profiles than GLPG1972 cross-species. Compound I demonstrated dose-dependent efficacy in two in vivo rat osteoarthritis models. In the experiment, the researchers used many compounds, for example, 1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1Application of 85692-37-1).

1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1) 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.Application of 85692-37-1

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

KIO₄-mediated Selective Hydroxymethylation/Methylenation of Imidazo-Heteroarenes: A Greener Approach was written by Franco, Marcelo Straesser;Saba, Sumbal;Rafique, Jamal;Braga, Antonio Luiz. And the article was included in Angewandte Chemie, International Edition in 2021.Synthetic Route of C18H21N3 This article mentions the following:

Herein, a KIO₄-mediated, sustainable and chemoselective approach for the one-pot C(sp²)-H bond hydroxymethylation or methylenation of imidazo-heteroarenes with formaldehyde, generated in situ via the oxidative cleavage of ethylene glycol or glycerol (renewable reagents) through the Malaprade reaction has been reported. In the presence of ethylene glycol, a series of 3-hydroxymethyl-imidazo-heteroarenes was obtained in good to excellent yields. These compounds are important intermediates to access pharmaceutical drugs, e.g., Zolpidem. Furthermore, by using glycerol, bis(imidazo[1,2-a]pyridin-3-yl)methane derivatives were selectively obtained in good to excellent yields. In the experiment, the researchers used many compounds, for example, N,N-Dimethyl-1-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)methanamine (cas: 106961-33-5Synthetic Route of C18H21N3).

N,N-Dimethyl-1-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)methanamine (cas: 106961-33-5) 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 based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Synthetic Route of C18H21N3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem