Month: October 2022

Thevenin, Marion; Chen, Gang; Kantham, Srinivas; Sun, Chunxiang; Glogauer, Michael; Young, Robert N. published their research in ACS Pharmacology & Translational Science in 2021. The article was titled 《Design, Synthesis, Pharmacokinetics, and Biodistribution of a Series of Bone-Targeting EP4 Receptor Agonist Prodrugs for Treatment of Osteoporosis and Other Bone Conditions》.Application of 17201-43-3 The article contains the following contents:

A series of bone-targeting EP4 receptor agonist conjugate prodrugs were prepared wherein a potent EP4 receptor agonist was bound to a biol. inactive, bisphosphonate-based bone-targeting moiety. Singly and doubly radiolabeled conjugates were synthesized and were shown to be stable in blood, to be rapidly eliminated from the bloodstream, and to be effectively taken up into bone in vivo after i.v. dosing. From these preliminary studies a preferred conjugate 4 (I)(also known as C3 and Mes-1007) was selected for follow up biodistribution and elimination studies. Doubly radiolabeled conjugate 4 was found to partition largely to the liver and bones, and both labels were eliminated from liver at the same rate indicating the conjugate was eliminated intact. Quantification of the labels in bones indicated that free EP4 agonist (EP4a)(2a) was released from bone-bound 4 with a half-time of about 7 days. When dosed orally, radiolabeled 4 was not absorbed and passed through the gastrointestinal tract essentially unchanged, and only traces of radiolabeled 4 were found in the liver, blood, or bones. 4 was found to bind rapidly and completely to powd. bone mineral or to various forms of calcium phosphate, forming a stable matrix suitable for implant and that could made into powders or solid forms and be sterilized without decomposition or release of 4. Basic hydrolysis released free EP4 agonist 2a (II) quant. from the material. In the experimental materials used by the author, we found 4-Cyanobenzyl bromide(cas: 17201-43-3Application of 17201-43-3)

4-Cyanobenzyl bromide(cas: 17201-43-3) is a white solid. Its melting point is 113-117°C, and flash point is 125.1°C. It is insoluble in water at 20°C. It is stable under normal temperatures and pressures. It should be stored at 0-5°C.Application of 17201-43-3

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Category: nitriles-buliding-blocksIn 2010 ,《New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Gommermann, Nina; Buehlmayer, Peter; von Matt, Anette; Breitenstein, Werner; Masuya, Keiichi; Pirard, Bernard; Furet, Pascal; Cowan-Jacob, Sandra W.; Weckbecker, Gisbert. The article conveys some information:

A novel series of pyrazolo[1,5a]pyrimidines was optimized to target lymphocyte-specific kinase (Lck). An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymic, cellular, and in vivo potency. In addition to this study using 2-(3-Bromophenyl)acetonitrile, there are many other studies that have used 2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5Category: nitriles-buliding-blocks) was used in this study.

2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5) has been used in the synthesis of a series of aminoethylbiphenyls, novel 5-HT7 receptor ligands or 2-(1-cyano-1-(3-bromophenyl))methylidene-3-phenylthiazolidine-4,5-dione.Category: nitriles-buliding-blocks

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of C7H4BrNIn 2022 ,《Discovery of G2019S-Selective Leucine Rich Repeat Protein Kinase 2 inhibitors with in vivo efficacy》 appeared in European Journal of Medicinal Chemistry. The author of the article were Lesniak, Robert K.; Nichols, R. Jeremy; Schonemann, Marcus; Zhao, Jing; Gajera, Chandresh R.; Fitch, William L.; Lam, Grace; Nguyen, Khanh C.; Smith, Mark; Montine, Thomas J.. The article conveys some information:

The discovery and development of compound I, an indazole-based, G2019S-selective (>2000-fold vs. WT) LRRK2 inhibitor capable of entering rodent brain (Kp = 0.5) and selectively inhibiting G2019S-LRRK2 was reported. The compounds disclosed herein present a starting point for further development of brain penetrant G2019S selective inhibitors that hopefully reduce lung phenotype side-effects and pave the way to providing a precision medicine for people with PD who carry the G2019S mutation. In the part of experimental materials, we found many familiar compounds, such as 2-Bromobenzonitrile(cas: 2042-37-7Synthetic Route of C7H4BrN)

2-Bromobenzonitrile(cas: 2042-37-7) belongs to a group of ortho-substituted bromobenzenes that have varying hepatotoxicity effects in the presence of rat liver microsomes in vitro. 2-Bromobenzonitrile is also used as a starting material to synthesize novel benzothiophene derivatives that were found to exhibit antibacterial and antifungal activity.Synthetic Route of C7H4BrN

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 105942-08-3In 2019 ,《Manufacture of the PI3K β-Sparing Inhibitor Taselisib. Part 2: Development of a Highly Efficient and Regioselective Late-Stage Process》 was published in Organic Process Research & Development. The article was written by St-Jean, Frederic; Remarchuk, Travis; Angelaud, Remy; Carrera, Diane E.; Beaudry, Danial; Malhotra, Sushant; McClory, Andrew; Kumar, Archana; Ohlenbusch, Gerd; Schuster, Andreas M.; Gosselin, Francis. The article contains the following contents:

A highly efficient and regioselective manufacturing route for the phosphoinositide 3-kinase β-sparing inhibitor taselisib (I) was developed. Highlights of the synthesis include: (1) magnesium-mediated formation of a challenging cyclic amidine; (2) regioselective imidazole construction via alkylation/condensation with bromopyruvic acid; and (3) triazole formation with 2-iso-Pr acetamidrazone to generate the key bromobenzoxazepine core intermediate. Subsequent highly efficient one-pot palladium-catalyzed Miyaura borylation/Suzuki cross-coupling/saponification, followed by a 1,1′-carbonyldiimidazole-mediated coupling with ammonia, led to the pentacyclic taselisib. This new synthetic approach provides a more efficient route to taselisib with a significant decrease in process mass intensity compared to the previous early development routes to the bromobenzoxazepine core. Finally, implementation of a controlled crystallization provided the active pharmaceutical ingredient with the desired polymorphic form.4-Bromo-2-fluorobenzonitrile(cas: 105942-08-3Related Products of 105942-08-3) was used in this study.

4-Bromo-2-fluorobenzonitrile(cas:105942-08-3) is used as a OLED intermediate, Pharmaceutical, electronic and chemical intermediate.Related Products of 105942-08-3 It is used in the synthesis of heterocycles and liquid crystals.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

COA of Formula: C9H7NOIn 2019 ,《Highly efficient thermally activated delayed fluorescence emitter developed by replacing carbazole with 1,3,6,8-tetramethyl-carbazole》 was published in Frontiers in Chemistry (Lausanne, Switzerland). The article was written by Cai, Jia-Lin; Liu, Wei; Wang, Kai; Chen, Jia-Xiong; Shi, Yi-Zhong; Zhang, Ming; Zheng, Cai-Jun; Tao, Si-Lu; Zhang, Xiao-Hong. The article contains the following contents:

Carbazole (Cz) is the one of the most popular electron donors to develop thermally activated delayed fluorescence (TADF) emitters, but addnl. groups are generally required in the mols. to enhance the steric hindrance between Cz and electron acceptor segments. To address this issue, we replaced Cz with its derivative 1,3,6,8-tetramethyl-carbazole (tMCz) to develop TADF emitters. Two novel compounds, 6-(4-(carbazol-9-yl)phenyl)-2,4-diphenylnicotinonitrile (CzPN) and 2,4-diphenyl-6-(4-(1,3,6,8-tetramethyl-carbazol-9-yl)phenyl) nicotinonitrile (tMCzPN) were designed and synthesized accordingly. With the same and simple mol. framework, tMCzPN successfully exhibits TADF behavior, while CzPN is a non-TADF fluorophor, as the addnl. steric hindrance of Me groups leads to a more twisted structure of tMCzPN. In the organic light-emitting diodes (OLEDs), tMCzPN exhibits extremely high forward-viewing maximum external quantum efficiency of 26.0%, without any light out-coupling enhancement, which is significantly higher than that of 5.3% for CzPN. These results indicate that tMCzPN is an excellent TADF emitter and proves that tMCz is a more appropriate candidate than Cz to develop TADF emitters. In the part of experimental materials, we found many familiar compounds, such as 3-Oxo-3-phenylpropanenitrile(cas: 614-16-4COA of Formula: C9H7NO)

3-Oxo-3-phenylpropanenitrile(cas: 614-16-4) has been used in the synthesis of substituted naphtho[1,8-bc]pyrans. It was also used as building block in the preparation of 4H-pyrans, 2-pyridones, furans and carbocyclics.COA of Formula: C9H7NO

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

《Enantioselective H-bond-directing approach for trienamine-mediated reactions in asymmetric synthesis》 was published in Angewandte Chemie, International Edition in 2012. These research results belong to Albrecht, Lukasz; Cruz Acosta, Fabio; Fraile, Alberto; Albrecht, Anna; Christensen, Jannie; Jorgensen, Karl Anker. HPLC of Formula: 50743-32-3 The article mentions the following:

The first H-bond-directed trienamine-mediated [4+2] cycloaddition was developed, thereby demonstrating the viability of such an activation strategy. The reaction between diversely substituted 2,4-dienals and 3-cyanochromones proceeded smoothly and in a highly stereoselective manner in the presence of a squaramide-containing aminocatalyst. Furthermore, it was demonstrated that the obtained cycloadducts can be chemo- and diastereoselectively transformed into polycyclic products with high mol. and stereochem. complexity that possess up to five stereogenic centers. An unexpected stereochem. outcome of the reaction was observed and a rationalization of the results was provided. In the experimental materials used by the author, we found 6-Isopropyl-4-oxo-4H-chromene-3-carbonitrile(cas: 50743-32-3HPLC of Formula: 50743-32-3)

6-Isopropyl-4-oxo-4H-chromene-3-carbonitrile(cas: 50743-32-3) belongs to nitriles. Nitriles are found in many useful compounds. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons.HPLC of Formula: 50743-32-3

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

In 2012,Bioorganic & Medicinal Chemistry Letters included an article by Bryan, Marian C.; Biswas, Kaustav; Peterkin, Tanya A. N.; Rzasa, Robert M.; Arik, Leyla; Lehto, Sonya G.; Sun, Hong; Hsieh, Feng-Yin; Xu, Cen; Fremeau, Robert T.; Allen, Jennifer R.. Safety of 2-Methoxy-6-methylbenzonitrile. The article was titled 《Chromenones as potent bradykinin B1 antagonists》. The information in the text is summarized as follows:

A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone I was efficacious in a carrageenan-induced mech. hyperalgesia model for chronic pain. The experimental part of the paper was very detailed, including the reaction process of 2-Methoxy-6-methylbenzonitrile(cas: 53005-44-0Safety of 2-Methoxy-6-methylbenzonitrile)

2-Methoxy-6-methylbenzonitrile(cas: 53005-44-0) belongs to nitriles. Nitriles are found in many useful compounds. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Safety of 2-Methoxy-6-methylbenzonitrile Industrially, the main methods for producing nitriles are ammoxidation and hydrocyanation. Both routes are green in the sense that they do not generate stoichiometric amounts of salts.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Zhang, Mingkai; Xu, Peilin; Vendola, Alex J.; Allais, Christophe; Dechert Schmitt, Anne-Marie; Singer, Robert A.; Morken, James P. published an article in Angewandte Chemie, International Edition. The title of the article was 《Stereocontrolled Pericyclic and Radical Cycloaddition Reactions of Readily Accessible Chiral Alkenyl Diazaborolidines》.SDS of cas: 1019607-55-6 The author mentioned the following in the article:

In this paper is described an easily synthesized chiral diazaborolidine that is inexpensive, stable, and provides excellent stereoselection across a number of reaction classes. These versatile compounds possess utility in four different classes of cycloaddition reactions, offering good yield and stereoselectivity. X-ray structure anal. provides insight about the origin of stereocontrol. In the experiment, the researchers used 4-(Cyclopropylamino)benzonitrile(cas: 1019607-55-6SDS of cas: 1019607-55-6)

4-(Cyclopropylamino)benzonitrile(cas: 1019607-55-6) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).SDS of cas: 1019607-55-6

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

In 2006,Balskus, Emily P.; Jacobsen, Eric N. published 《α,β-Unsaturated β-silyl imide substrates for catalytic, enantioselective conjugate additions: A total synthesis of (+)-lactacystin and the discovery of a new proteasome inhibitor》.Journal of the American Chemical Society published the findings.Name: 2-(3-Bromophenyl)acetonitrile The information in the text is summarized as follows:

Chiral (salen)Al μ-oxo dimer catalyzes the highly enantioselective conjugate addition of carbon-centered nucleophiles to α,β-unsaturated silyl imides. Allyldimethylsilane-substituted imide I was identified as an optimal substrate, undergoing addition reactions with a variety of nitrile nucleophiles in high yield and enantiomeric excess. The silicon-containing products are synthetically useful chiral building blocks, as demonstrated by their application to an enantioselective total synthesis of the potent proteasome inhibitor (+)-lactacystin. Elaboration of lactam II to the natural product was effected in 12 steps and in 11% overall yield and proceeded through an unusual spiro β-lactone intermediate. This compound was found to inhibit the chymotrypsin-like site of the 26S proteasome at similar levels to known inhibitor clasto-lactacystin β-lactone (omuralide). In the experimental materials used by the author, we found 2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5Name: 2-(3-Bromophenyl)acetonitrile)

2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5) has been used in the synthesis of 2-(1-cyano-1-(3-bromophenyl))methylidene-3-phenylthiazolidine-4,5-dione or a series of aminoethylbiphenyls, novel 5-HT7 receptor ligands.Name: 2-(3-Bromophenyl)acetonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

In 2018,Kavala, Veerababurao; Yang, Zonghan; Konala, Ashok; Yang, Tang-Hao; Kuo, Chun-Wei; Ruan, Jian-Yao; Yao, Ching-Fa published 《Synthesis of 1,2,3-Fused Indole Polyheterocycles by Copper-Catalyzed Cascade Reaction》.European Journal of Organic Chemistry published the findings.Related Products of 31938-07-5 The information in the text is summarized as follows:

A one-pot reaction has been developed for the preparation of 1,2,3-fused indole polyheterocycles, e.g., I, by starting from 2-iodobenzamide and 2-iodobenzyl cyanide in the presence of a copper catalyst. The cascade process involves the efficient formation of one C-C and three C-N bonds. A broad substrate scope, good yields, and short reactions times are key features of this strategy. The experimental process involved the reaction of 2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5Related Products of 31938-07-5)

2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5) has been used in the synthesis of 2-(1-cyano-1-(3-bromophenyl))methylidene-3-phenylthiazolidine-4,5-dione or a series of aminoethylbiphenyls, novel 5-HT7 receptor ligands.Related Products of 31938-07-5

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts