Category: 15777-70-5

Sulfonamidopyrrolidinone Factor Xa Inhibitors: Potency and Selectivity Enhancements via P-1 and P-4 Optimization was written by Choi-Sledeski, Yong Mi;McGarry, Daniel G.;Green, Daniel M.;Mason, Helen J.;Becker, Michael R.;Davis, Roderick S.;Ewing, William R.;Dankulich, William P.;Manetta, Vincent E.;Morris, Robert L.;Spada, Alfred P.;Cheney, Daniel L.;Brown, Karen D.;Colussi, Dennis J.;Chu, Valeria;Heran, Christopher L.;Morgan, Suzanne R.;Bentley, Ross G.;Leadley, Robert J.;Maignan, Sebastien;Guilloteau, Jean-Pierre;Dunwiddie, Christopher T.;Pauls, Henry W.. And the article was included in Journal of Medicinal Chemistry in 1999.Recommanded Product: 15777-70-5 This article mentions the following:

Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy- and 4-aminobenzamidines were discovered to be effective inhibitors of fXa. X-ray crystallog. experiments in trypsin and mol. modeling studies suggest that our inhibitors bind by insertion of the 4-hydroxybenzamidine moiety into the S-1 subsite of the fXa active site. Of the P-4 groups examined, the pyridylthienyl sulfonamides were found to confer excellent potency and selectivity especially in combination with 4-hydroxybenzamidine. Compound I (RPR130737) was shown to be a potent fXa inhibitor (K_i = 2 nM) with selectivity against structurally related serine proteinases (>1000 times). Preliminary biol. evaluation demonstrates the effectiveness of this inhibitor in common assays of thrombosis in vitro (e.g. activated partial thromboplastin time) and in vivo (e.g. rat FeCl₂-induced carotid artery thrombosis model). In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Recommanded Product: 15777-70-5).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Recommanded Product: 15777-70-5

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Absolute proton affinities of some substituted toluenes: the additivity rule of thumb for ipso attack was written by Eckert-Maksic, Mirjana;Knezevic, Andrea;Maksic, Zvonimir B.. And the article was included in Journal of Physical Organic Chemistry in 1998.Reference of 15777-70-5 This article mentions the following:

The problem of the ipso protonation of toluene and its predominantly disubstituted derivatives was considered by the MP2(fc)/6-31G^**//HF/6-31G^*+ZPE(HF/6-31G^*) theor. model. The substituents involved covered a wide range of different donor-acceptor capabilities. It is shown that the calculated MP2 ipso proton affinities of substituted toluenes follow mutatis mutandis the same additivity rule which was found earlier to be operative in polysubstituted benzenes, naphthalenes and biphenylenes. The additivity equation is both intuitively appealing and useful, being able to offer quant. estimates of the proton affinity by very simple calculation It is based on the concept of the increment, which in turn describes the influence of a single substituent on the proton affinity. Any substituent behaves as a rule as if the other were non-existent, thus giving rise to the independent substituent approximation (ISA). The performance of the additivity rule of thumb is very good, as evidenced by the average absolute deviation of 1 kcal mol^-1. Larger deviations are possible, but they rarely occur, being indicative of a difference in interactions between substituents in the initial neutral base and in the final cationic conjugate acid. Finally, it follows as a corollary of the present anal. that protonation ipso to the CH₃ group is never thermodynamically the most favorable site of proton attack in the benzene ring, provided that there is a single unsubstituted carbon atom within the aromatic moiety. The relevance of ipso protonation in persubstituted benzenes is briefly discussed. In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Reference of 15777-70-5).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Under appropriate conditions, inorganic acids also react with alcohols to form esters. To form these esters, a wide variety of specialized reagents and conditions can be used. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Reference of 15777-70-5

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Practical imidazole-based phosphine ligands for selective palladium-catalyzed hydroxylation of aryl halides was written by Schulz, Thomas;Torborg, Christian;Schaeffner, Benjamin;Huang, Jun;Zapf, Alexander;Kadyrov, Renat;Boerner, Armin;Beller, Matthias. And the article was included in Angewandte Chemie, International Edition in 2009.Name: 4-Hydroxy-3-methylbenzonitrile This article mentions the following:

Novel imidazole-based phosphine ligands are synthesized on scales up to 100 g by a convenient lithiation-phosphorylation method. The phosphines are stable towards air and moisture and are successfully applied as ligands in the palladium-catalyzed selective hydroxylation of aryl halides. In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Name: 4-Hydroxy-3-methylbenzonitrile).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are about as acidic as water, and most other alcohols are somewhat less acidic. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.Name: 4-Hydroxy-3-methylbenzonitrile

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Sulfonamidopyrrolidinone Factor Xa Inhibitors: Potency and Selectivity Enhancements via P-1 and P-4 Optimization was written by Choi-Sledeski, Yong Mi;McGarry, Daniel G.;Green, Daniel M.;Mason, Helen J.;Becker, Michael R.;Davis, Roderick S.;Ewing, William R.;Dankulich, William P.;Manetta, Vincent E.;Morris, Robert L.;Spada, Alfred P.;Cheney, Daniel L.;Brown, Karen D.;Colussi, Dennis J.;Chu, Valeria;Heran, Christopher L.;Morgan, Suzanne R.;Bentley, Ross G.;Leadley, Robert J.;Maignan, Sebastien;Guilloteau, Jean-Pierre;Dunwiddie, Christopher T.;Pauls, Henry W.. And the article was included in Journal of Medicinal Chemistry in 1999.Recommanded Product: 15777-70-5 This article mentions the following:

Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy- and 4-aminobenzamidines were discovered to be effective inhibitors of fXa. X-ray crystallog. experiments in trypsin and mol. modeling studies suggest that our inhibitors bind by insertion of the 4-hydroxybenzamidine moiety into the S-1 subsite of the fXa active site. Of the P-4 groups examined, the pyridylthienyl sulfonamides were found to confer excellent potency and selectivity especially in combination with 4-hydroxybenzamidine. Compound I (RPR130737) was shown to be a potent fXa inhibitor (K_i = 2 nM) with selectivity against structurally related serine proteinases (>1000 times). Preliminary biol. evaluation demonstrates the effectiveness of this inhibitor in common assays of thrombosis in vitro (e.g. activated partial thromboplastin time) and in vivo (e.g. rat FeCl₂-induced carotid artery thrombosis model). In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Recommanded Product: 15777-70-5).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Recommanded Product: 15777-70-5

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Absolute proton affinities of some substituted toluenes: the additivity rule of thumb for ipso attack was written by Eckert-Maksic, Mirjana;Knezevic, Andrea;Maksic, Zvonimir B.. And the article was included in Journal of Physical Organic Chemistry in 1998.Reference of 15777-70-5 This article mentions the following:

The problem of the ipso protonation of toluene and its predominantly disubstituted derivatives was considered by the MP2(fc)/6-31G^**//HF/6-31G^*+ZPE(HF/6-31G^*) theor. model. The substituents involved covered a wide range of different donor-acceptor capabilities. It is shown that the calculated MP2 ipso proton affinities of substituted toluenes follow mutatis mutandis the same additivity rule which was found earlier to be operative in polysubstituted benzenes, naphthalenes and biphenylenes. The additivity equation is both intuitively appealing and useful, being able to offer quant. estimates of the proton affinity by very simple calculation It is based on the concept of the increment, which in turn describes the influence of a single substituent on the proton affinity. Any substituent behaves as a rule as if the other were non-existent, thus giving rise to the independent substituent approximation (ISA). The performance of the additivity rule of thumb is very good, as evidenced by the average absolute deviation of 1 kcal mol^-1. Larger deviations are possible, but they rarely occur, being indicative of a difference in interactions between substituents in the initial neutral base and in the final cationic conjugate acid. Finally, it follows as a corollary of the present anal. that protonation ipso to the CH₃ group is never thermodynamically the most favorable site of proton attack in the benzene ring, provided that there is a single unsubstituted carbon atom within the aromatic moiety. The relevance of ipso protonation in persubstituted benzenes is briefly discussed. In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Reference of 15777-70-5).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Under appropriate conditions, inorganic acids also react with alcohols to form esters. To form these esters, a wide variety of specialized reagents and conditions can be used. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Reference of 15777-70-5

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Practical imidazole-based phosphine ligands for selective palladium-catalyzed hydroxylation of aryl halides was written by Schulz, Thomas;Torborg, Christian;Schaeffner, Benjamin;Huang, Jun;Zapf, Alexander;Kadyrov, Renat;Boerner, Armin;Beller, Matthias. And the article was included in Angewandte Chemie, International Edition in 2009.Name: 4-Hydroxy-3-methylbenzonitrile This article mentions the following:

Novel imidazole-based phosphine ligands are synthesized on scales up to 100 g by a convenient lithiation-phosphorylation method. The phosphines are stable towards air and moisture and are successfully applied as ligands in the palladium-catalyzed selective hydroxylation of aryl halides. In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Name: 4-Hydroxy-3-methylbenzonitrile).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are about as acidic as water, and most other alcohols are somewhat less acidic. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.Name: 4-Hydroxy-3-methylbenzonitrile

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Liquid-crystal compounds. VIII. Methyl-substituted p-alkyl- and p-alkoxycinnamic acids and their cyanophenyl esters was written by Pavlyuchenko, A. I.;Smirnova, N. I.;Kovshev, E. I.;Titov, V. V.. And the article was included in Zhurnal Organicheskoi Khimii in 1976.SDS of cas: 15777-70-5 This article mentions the following:

P-RC6H4CH:CMeCO2H (I; R = Bu, pentyl, hexyl) were prepared in 18.4-21.1% yield by reaction of RC6H4CHO with MeCHBrCO2Et followed by hydrolysis; their p-cyanophenyl esters were prepared by standard procedures. The p-RC6H4CMe:CHCO2H (II; R = Bu, pentyl, hexyl, heptyl, octyl) were prepared in 20.1-25.0% yield by condensation of p-RC6H4COMe with HOAc; their p-cyanophenyl esters were also prepared Six III (R = Bu, heptyl; R1 = 2- and 3-Me, H; R2 = 2- and 3-Me, H) were also prepared by standard methods. In I, II, and III the temperature of clearing was lowered and the mesomorphic interval narrowed with respect to the unsubstituted compounds II have a wider mesomorphic range than p-alkylcinnamic acids. In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5SDS of cas: 15777-70-5).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.SDS of cas: 15777-70-5

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Reductive desilanolation as a route to benzonitriles. An application to a concise synthesis of the aromatic sector of calicheamicin was written by Olson, Steven H.;Danishefsky, Samuel. And the article was included in Tetrahedron Letters in 1994.Product Details of 15777-70-5 This article mentions the following:

The TMS-cyanohydrins of quinones undergo reductive desilanolation in the presence of samarium iodide to form hydroxybenzonitriles. Benzoquinone I was converted to the hexasubstituted aromatic fragment of calicheamicin II by this method. In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Product Details of 15777-70-5).

4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom for the hydroxyl group. A multistep synthesis may use Grignard-like reactions to form an alcohol with the desired carbon structure, followed by reactions to convert the hydroxyl group of the alcohol to the desired functionality.Product Details of 15777-70-5

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts