Tag: 100-200

Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL) was written by Borkin, Dmitry;Pollock, Jonathan;Kempinska, Katarzyna;Purohit, Trupta;Li, Xiaoqin;Wen, Bo;Zhao, Ting;Miao, Hongzhi;Shukla, Shirish;He, Miao;Sun, Duxin;Cierpicki, Tomasz;Grembecka, Jolanta. And the article was included in Journal of Medicinal Chemistry in 2016.Quality Control of 5-Methyl-2-nitrobenzonitrile This article mentions the following:

Development of potent small mol. inhibitors of protein-protein interactions with optimized druglike properties represents a challenging task in lead optimization process. Here, we report synthesis and structure-based optimization of new thienopyrimidine class of compounds, which block the protein-protein interaction between menin and MLL fusion proteins that plays an important role in acute leukemias with MLL translocations. We performed simultaneous optimization of both activity and druglike properties through systematic exploration of substituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable for in vivo studies in mice. This work resulted in the identification of compound 27 (MI-538), which showed significantly increased activity, selectivity, polarity, and pharmacokinetic profile over 1 and demonstrated a pronounced effect in a mouse model of MLL leukemia. This study, which reports detailed structure-activity and structure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing inhibitors of protein-protein interactions for potential therapeutic applications. In the experiment, the researchers used many compounds, for example, 5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6Quality Control of 5-Methyl-2-nitrobenzonitrile).

5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. Quality Control of 5-Methyl-2-nitrobenzonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Antituberculous compounds. III. p-Alkoxy-N-arylbenzamidines was written by Partridge, M. W.. And the article was included in Journal of the Chemical Society in 1949.Electric Literature of C11H13NO This article mentions the following:

As an extension of experiments on the relation between structure and activity against Mycobacterium tuberculosis of N-substituted amidines, a series of p-alkoxy-N-arylbenzamidines and certain analogs have been prepared Although high activities were observed in vitro in several cases, no activity could be demonstrated in vivo. p-NCC₆H₄ONa (prepared with 1 equivalent of Na in EtOH) and 1 equivalent of RCl, refluxed 16-20 h., give the following p-alkoxylphenyl cyanides (I), p-ROC₆H₄CN (R given): Pr, b₃ 121-2°, m. 47°, 54%; Bu, b₃ 146-8°, m. 35°, 80%; hexyl, b₃ 155-7°, m. 32°, 71%; octyl, b₂ 171-3 °, 70%; allyl, m. 43°, 72%; iso-Bu, b₁ 114-16°, 35%. The I and an equivalent of an arylammonium benzenesulfonate, heated 1-4 h. at 180-210°, give the following N-phenylbenzamidines, p-ROC₆H₄C(:NH)NHPh (R given): Me (benzenesulfonate, m. 186-7°, 51%); Et, m. 143.5-4.5°, 55% (benzenesulfonate, m. 168-9°); Pr, m. 128-9°, 72%; Bu, m. 121-2°, 90%; iso-Bu, m. 131-2°, 88%; allyl, m. 115-17°, 28% (low yield a result of reduced heating period to avoid Claisen rearrangement of the cyanide); hexyl, m. 122-4°, 90%; octyl, m. 118-19°, 90%. p-MeOC₆H₄CN (13.3 g.) and 9.4 g. 2-aminopyridine at 60°, treated (5 min.) with 13.3 g. AlCl₃ and heated 20 min. at 200°, give 5.4 g. unchanged p-MeOC₆H₄CN and 24% p-methoxy-N-(2-pyridyl)benzamidine, m. 107-8°. p-MeOC₆H₄C(:NPh)Cl (30 g.) and 12 g. PhNH₂ in 100 cc. C₆H₆, refluxed 3 h., give 78% of the chloride, m. 269-70° (decomposition), of p-methoxy-N,N’-diphenylbenzamidine, m. 107-8°. p-BuOC₆H₄COCl (51.2 g.) and 70 cc. 2 N NaOH, gradually added to 22.3 g. PhNH₂ in 50 cc. 2 N NaOH, give 76% p-butoxybenzanilide (II), m. 147°; II, PhNH₂, and PCl₅ give 96% p-butoxy-N,N’-diphenylbenzamidine, m. 111°. p-H₂NC₆H₄CO₂Et and PhSO₃H give p-carbethoxyanilinium benzenesulfonate, m. 194-5°; p-butoxy-N-(p-carbethoxyphenyl)benzamidine, m. 138.5-9.5°, 43%; refluxed 6 h. with 5 N NaOH, there results 78% of the free acid, m. 249-50° (decomposition). p-Butoxy-N-(p-chlorophenyl)benzamidine, m. 151-2°, 50%; N-(p-butoxyphenyl) analog, m. 149-50°, 60%. The relation between structure and activity of these compounds against M. tuberculosis is discussed. The activities of the more active members of this series are decreased by serum, although some of the compounds retain activities of the order of 1:100,000. In the experiment, the researchers used many compounds, for example, 4-iso-Butoxybenzonitrile (cas: 5203-15-6Electric Literature of C11H13NO).

4-iso-Butoxybenzonitrile (cas: 5203-15-6) belongs to nitriles. There has been no report on the microbial biosynthesis of nitriles and the physiological function of such enzymes, nor was it not even known whether aliphatic and aromatic nitriles are biological compounds or just petrochemicals. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Electric Literature of C11H13NO

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Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthesis and in vitro acetylcholinesterase and butrylcholinesterase inhibitory activity of tacrine (cognex) derivatives was written by Gregor, Vlad E.;Emmerling, Mark R.;Lee, Chitase;Moore, Catherine J.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 1992.Product Details of 53312-77-9 This article mentions the following:

Chlorosubstituted derivatives of tacrine, I (X = H, 5-, 6-, 7-, 8-Cl, n = 0), and of 1,4-methylenetacrine, I (n = 1), and their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities are described. Thus, 2-aminobenzonitriles II (X = H, 3-, 4-, 5-, 6-Cl) cyclized with cyclohexanone or norcamphor to give I (n = 0, 1), resp. The most potent analogs are 6-chlorotacrine I (X = 6-Cl, n = 0) in AChE and 7-chlorotacrine I (X = 7-Cl, n = 0) in BChE inhibition. In the experiment, the researchers used many compounds, for example, 2-Amino-3-chlorobenzonitrile (cas: 53312-77-9Product Details of 53312-77-9).

2-Amino-3-chlorobenzonitrile (cas: 53312-77-9) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. Some nitriles are manufactured by heating carboxylic acids with ammonia in the presence of catalysts. This process is used to make nitriles from natural fats and oils, the products being used as softening agents in synthetic rubbers, plastics, and textiles and for making amines.Product Details of 53312-77-9

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Oxidative fluorination of arenes was written by Meurs, Jan H. H.;Sopher, David W.;Eilenberg, Wolf. And the article was included in Angewandte Chemie in 1989.COA of Formula: C7H4FNO This article mentions the following:

Phenol and benzene derivatives underwent selective oxidative fluorination by HF-base mixture Thus, treatment of phenol with PbO₂, HF, and pyridine afforded 50% 4,4-difluoro-2,5-cyclohexadienone. The latter was formed in 25% yield by anodic oxidation of phenol in the presence HF-Et₃N. In the experiment, the researchers used many compounds, for example, 2-Fluoro-5-hydroxybenzenecarbonitrile (cas: 104798-53-0COA of Formula: C7H4FNO).

2-Fluoro-5-hydroxybenzenecarbonitrile (cas: 104798-53-0) belongs to nitriles. There has been no report on the microbial biosynthesis of nitriles and the physiological function of such enzymes, nor was it not even known whether aliphatic and aromatic nitriles are biological compounds or just petrochemicals. 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.COA of Formula: C7H4FNO

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Substituent Effects on the Thermochemistry of Thiophenes. A Theoretical (G3(MP2)//B3LYP and G3) Study was written by Notario, Rafael;Temprado, Manuel;Roux, Maria Victoria;Liebman, Joel F.. And the article was included in Journal of Physical Chemistry A in 2012.Name: 3-Methylthiophene-2-carbonitrile This article mentions the following:

Very good linear correlations between exptl. and calculated enthalpies of formation in the gas phase (G3(MP2)//B3LYP and G3) for 48 thiophene derivatives were obtained. These correlations permit a correction of the calculated enthalpies of formation to estimate more reliable exptl. values for the enthalpies of formation of substituted thiophenes, check the reliability of exptl. measurements, and also predict the enthalpies of formation of new thiophenes that are not available in the literature. Also, the difference between the enthalpies of formation of isomeric thiophenes with the same substituent in positions 2 and 3 of the ring was analyzed. Likewise, a comparison of the substituent effect in the thiophene and benzene rings was established. In the experiment, the researchers used many compounds, for example, 3-Methylthiophene-2-carbonitrile (cas: 55406-13-8Name: 3-Methylthiophene-2-carbonitrile).

3-Methylthiophene-2-carbonitrile (cas: 55406-13-8) belongs to nitriles. There has been no report on the microbial biosynthesis of nitriles and the physiological function of such enzymes, nor was it not even known whether aliphatic and aromatic nitriles are biological compounds or just petrochemicals. 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.Name: 3-Methylthiophene-2-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Discovery of a Potent and Selective PI3Kδ Inhibitor (S)-2,4-Diamino-6-((1-(7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile with Improved Pharmacokinetic Profile and Superior Efficacy in Hematological Cancer Models was written by Shukla, Manojkumar R.;Patra, Sukanya;Verma, Mahip;Sadasivam, Gayathri;Jana, Nirmal;Mahangare, Sachin J.;Vidhate, Prashant;Lagad, Dipak;Tarage, Anand;Cheemala, Murthy;Kulkarni, Chaitanya;Bhagwat, Shankar;Chaudhari, Vinod D.;Sayyed, Majid;Pachpute, Vipul;Phadtare, Ramesh;Gole, Gopal;Phukan, Samiron;Sunkara, Brahmam;Samant, Charudatt;Shingare, Manisha;Naik, Aditya;Trivedi, Sneha;Marisetti, Ajit Kumar;Reddy, Madhusudhan;Gholve, Milind;Mahajan, Nilesh;Sabde, Sudeep;Patil, Vinod;Modi, Dipak;Mehta, Maneesh;Nigade, Prashant;Tamane, Kaustubh;Tota, Swati;Goyal, Hemant;Volam, Harish;Pawar, Shashikant;Ahirrao, Prajakta;Dinchhana, Lal;Mallurwar, Sadanand;Akarte, Atul;Bokare, Anand;Kanhere, Rupesh;Reddy, Neetinkumar;Koul, Sarita;Dandekar, Manoj;Singh, Minakshi;Bernstein, Peter R.;Narasimham, Lakshmi;Bhonde, Mandar;Gundu, Jayasagar;Goel, Rajan;Kulkarni, Sanjeev;Sharma, Sharad;Kamboj, Rajender Kumar;Palle, Venkata P.. And the article was included in Journal of Medicinal Chemistry in 2020.Application of 60025-09-4 This article mentions the following:

PI3Kδ inhibitors have been approved for B-cell malignancies like CLL, small lymphocytic lymphoma, and so forth. However, currently available PI3Kδ inhibitors are nonoptimal, showing weakness against at least one of the several important properties: potency, isoform selectivity, and/or pharmacokinetic profile. To come up with a PI3Kδ inhibitor that overcomes all these deficiencies, a pharmacophoric expansion strategy was employed. Herein, we describe a systematic transformation of a “three-blade propeller” shaped lead, 2,3-disubstituted quinolizinone 11, through a 1,2-disubstituted quinolizinone 20 to a novel “four-blade propeller” shaped 1,2,3-trisubstituted quinolizinone 34. Compound 34 (I)has excellent potency, isoform selectivity, metabolic stability across species, and exhibited a favorable pharmacokinetic profile. Compound 34 also demonstrated a differentiated efficacy profile in human germinal center B and activated B cell-DLBCL cell lines and xenograft models. Compound 34 qualifies for further evaluation as a candidate for monotherapy or in combination with other targeted agents in DLBCLs and other forms of iNHL. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Application of 60025-09-4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Application of 60025-09-4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Solvent-free synthesis of 2-aminothiophene-3-carbonitrile derivatives using high-speed vibration milling was written by Xu, Fang;Li, Yujin;Xu, Fengshuang;Ye, Qing;Han, Liang;Gao, Jianrong;Yu, Wubin. And the article was included in Journal of Chemical Research in 2014.Quality Control of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile This article mentions the following:

Solvent-free synthesis of 2-aminothiophene-3-carbonitrile derivatives e.g., I via one-pot cyclo-condensation of various ketones, malononitrile with elemental sulfur employing high-speed vibration milling with diethylamine as the catalyst was developed. The main advantages of this method are short reaction times, facile conditions, good yields, use of inexpensive catalyst and environmental friendly conditions. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Quality Control of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile).

2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. Quality Control of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

The reduction of α,β-unsaturated nitriles and α-halonitriles with sodium hydrogen telluride was written by Blay, Gonzalo;Cardona, Luz;Garcia, Begona;Lahoz, Luisa;Pedro, Jose R.. And the article was included in Tetrahedron in 1996.Safety of 2-Cyclohexylacetonitrile This article mentions the following:

Sodium hydrogen telluride reacts chemoselectively with α,β-unsaturated nitriles and α-halonitriles linked to aromatic and aliphatic substituents to give the corresponding saturated nitriles with good yields. In the experiment, the researchers used many compounds, for example, 2-Cyclohexylacetonitrile (cas: 4435-14-7Safety of 2-Cyclohexylacetonitrile).

2-Cyclohexylacetonitrile (cas: 4435-14-7) belongs to nitriles. Nitrile carbon shifts are in the range of 115�25 ppm whereas in isonitriles the shifts are around 155�65 ppm. 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.Safety of 2-Cyclohexylacetonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Cobalt(II)/TPPMS-Catalyzed Dehydrative Nucleophilic Substitution of Alcohols in Water was written by Hikawa, Hidemasa;Ijichi, Yukiko;Kikkawa, Shoko;Azumaya, Isao. And the article was included in European Journal of Organic Chemistry in 2017.Computed Properties of C8H5F3N2 This article mentions the following:

A green and sustainable direct dehydrative amination of alcs., catalyzed by cobalt(II)/TPPMS (sodium diphenylphosphinobenzene-3-sulfonate) in water, is described. Earth-abundant cobalt was used as Co(hfac)₂·xH₂O (hfac: hexafluoroacetylacetone), which acts as a highly efficient Lewis acidic catalyst. This simple atom-economical protocol features mild conditions without the need for a base or other additives and affords the corresponding benzylic and allylic anilines along with water as the only coproduct. Mechanistic studies suggest that this system is driven by direct nucleophilic substitution of alcs. In the experiment, the researchers used many compounds, for example, 2-Amino-4-(trifluoromethyl)benzonitrile (cas: 1483-54-1Computed Properties of C8H5F3N2).

2-Amino-4-(trifluoromethyl)benzonitrile (cas: 1483-54-1) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. Some nitriles are manufactured by heating carboxylic acids with ammonia in the presence of catalysts. This process is used to make nitriles from natural fats and oils, the products being used as softening agents in synthetic rubbers, plastics, and textiles and for making amines.Computed Properties of C8H5F3N2

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

β-Amino alcohols as ligands for asymmetric transfer hydrogenation of ketones in water was written by Wu, Xiaofeng;Li, Xiaohong;McConville, Matthew;Saidi, Ourida;Xiao, Jianliang. And the article was included in Journal of Molecular Catalysis A: Chemical in 2006.HPLC of Formula: 101219-69-6 This article mentions the following:

Chiral β-amino alcs. were used as ligands for ruthenium, rhodium and iridium-catalyzed asym. transfer hydrogenation of acetophenone derivatives in water with formate as reductant. The catalysts were shown to be capable of asym. transfer hydrogenation of ketones in water, but their activities and enantioselectivity varied with the ligands used and with solution pH values, with higher pH favoring higher rates and better enantioselectivity. In the experiment, the researchers used many compounds, for example, (R)-4-(1-Hydroxyethyl)benzonitrile (cas: 101219-69-6HPLC of Formula: 101219-69-6).

(R)-4-(1-Hydroxyethyl)benzonitrile (cas: 101219-69-6) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.HPLC of Formula: 101219-69-6

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts