Month: January 2023

Soluble 2-Substituted Aminopyrido[2,3-d]pyrimidin-7-yl Ureas. Structure-Activity Relationships against Selected Tyrosine Kinases and Exploration of in Vitro and in Vivo Anticancer Activity was written by Schroeder, Mel C.;Hamby, James M.;Connolly, Cleo J. C.;Grohar, Patrick J.;Winters, R. Thomas;Barvian, Mark R.;Moore, Charles W.;Boushelle, Stacey L.;Crean, Sheila M.;Kraker, Alan J.;Driscoll, Denise L.;Vincent, Patrick W.;Elliott, William L.;Lu, Gina H.;Batley, Brian L.;Dahring, Tawny K.;Major, Terry C.;Panek, Robert L.;Doherty, Annette M.;Showalter, H. D. Hollis. And the article was included in Journal of Medicinal Chemistry in 2001.SDS of cas: 67197-53-9 This article mentions the following:

In a search for medicinal agents to treat proliferative diseases, 2-substituted aminopyrido[2,3-d]pyrimidin-7-ylureas were discovered as a novel class of soluble, potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was developed that enabled the synthesis of a wide variety of analogs with substitution on several positions of the template. From the lead structure, 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-2-yl]-3-tert.-butylurea , several series of analogs were made that examined the C-6 aryl substituent, a variety of water solubilizing substituents at the C-2 position, and urea or other acyl functionality at the N-7 position. Compounds of this series were competitive with ATP and displayed submicromolar to low nanomolar potency against a panel of TKs, including receptor (platelet-derived growth factor, PDGFr; fibroblast growth factor, FGFr;) and non-receptor (c-Src) classes. Several of the most potent compounds displayed submicromolar inhibition of PDGF-mediated receptor autophosphorylation in rat aortic vascular smooth muscle cells and low micromolar inhibition of cellular growth in five human tumor cell lines. One of the more thoroughly evaluated members, I, with IC₅₀ values of 0.21 μM (PDGFr), 0.049 μM (bFGFr), and 0.018 μM (c-Src), was evaluated in in vivo studies against a panel of five human tumor xenografts, with known and/or inferred dependence on the EGFr, PDGFr, and c-Src TKs. I produced a tumor growth delay of 14 days against the Colo-205 colon xenograft model. In the experiment, the researchers used many compounds, for example, 2-(2,6-Dibromophenyl)acetonitrile (cas: 67197-53-9SDS of cas: 67197-53-9).

2-(2,6-Dibromophenyl)acetonitrile (cas: 67197-53-9) belongs to nitriles. The electronic structure of nitriles is very similar to that of an alkyne with the main difference being the presence of a set of lone pair electrons on the nitrogen. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.SDS of cas: 67197-53-9

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Copper-catalyzed direct amination of benzylic hydrocarbons and inactive aliphatic alkanes with arylamines was written by Yao, Hua;Xie, Bo;Zhong, Xiaoyang;Jin, Shengzhou;Lin, Sen;Yan, Zhaohua. And the article was included in Organic & Biomolecular Chemistry in 2020.Related Products of 10282-32-3 This article mentions the following:

A new synthetic method toward direct C-N bond formation through saturated C-H amination of benzylic hydrocarbons RCH₂R¹ (R = H, Me, Et; R¹ = Ph, 2-chlorophenyl, 3,5-dimethylphenyl, etc.) and inactive aliphatic alkanes such as cyclohexane with primary aromatic amines R²NH₂ (R² = Ph, 3-bromophenyl, pyridin-2-yl, pyrazin-2-yl, etc.) under an inexpensive catalyst/oxidant (Cu/DTBP) system has been developed. Both aminopyridines and anilines could react smoothly with primary and secondary benzylic C-H substrates or cyclohexane to form the corresponding aromatic secondary amines R²NHCH(R)R¹ or C₆H₁₁NHR² in moderate to good yields. This protocol has the advantages of wide functional group tolerance and use of readily available raw materials. In the experiment, the researchers used many compounds, for example, 4-(Benzylamino)benzonitrile (cas: 10282-32-3Related Products of 10282-32-3).

4-(Benzylamino)benzonitrile (cas: 10282-32-3) 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. Related Products of 10282-32-3

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Conformationally restricted quinazolone derivatives as PI3Kδ-selective inhibitors: the design, synthesis and biological evaluation was written by Ma, Xiaodong;Fang, Fang;Tao, Qiangqiang;Shen, Li;Zhong, Guochen;Qiao, Tao;Lv, Xiaoqing;Li, Jiaming. And the article was included in MedChemComm in 2019.Reference of 60025-09-4 This article mentions the following:

A series of structurally novel quinazolone-based PI3Kδ-selective inhibitors were designed and synthesized via the approach of conformational restriction. The majority of them exhibited two-digit to single-digit nanomolar IC₅₀ values against PI3Kδ, along with low micromolar to submicromolar GI₅₀ values against human malignant B-cell line SU-DHL-6. The representative compound, with the most potent PI3Kd inhibitory activity (IC₅₀ = 6.3 nM) and anti-proliferative activity (GI₅₀ = 0.21 μM) in this series, was further evaluated for its PI3Kδ selectivity, capability to down-regulate PI3K signaling in SU-DHL-6 cells, in vitro metabolic stability, and pharmacokinetic (PK) properties. The exptl. results illustrated that this compound, as a promising lead, merits extensive structural optimization for exploring novel PI3Kδ-selective inhibitors as clin. candidates. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Reference of 60025-09-4).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) 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. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Reference of 60025-09-4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

A metalloligand appended with benzimidazole rings: tetranuclear [CoZn₃] and [CoCd₃] complexes and their catalytic applications was written by Pandey, Saurabh;Bansal, Deepak;Gupta, Rajeev. And the article was included in New Journal of Chemistry in 2018.Related Products of 55490-87-4 This article mentions the following:

A novel Co³⁺-based metalloligand 1 offering appended benzimidazole rings was prepared and used for the synthesis of tetranuclear [CoZn₃] (2 and 2-Cl, 4) and [CoCd₃] (3) heterometallic coordination complexes (HCCs). Crystallog. studies of 2-Cl and 3 illustrate coordination of three secondary metal ions (Zn²⁺/Cd²⁺) to the appended benzimidazole rings of 1 thus producing tetranuclear HCCs. Both HCCs were used as heterogeneous catalysts for Knoevenagel condensation and Henry reactions. The stability and recyclability experiments illustrate the stable nature of both HCCs during the catalysis. In the experiment, the researchers used many compounds, for example, 2-(Anthracen-9-ylmethylene)malononitrile (cas: 55490-87-4Related Products of 55490-87-4).

2-(Anthracen-9-ylmethylene)malononitrile (cas: 55490-87-4) 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. In addition, Nitriles can react with alkynes, which leads to an increase in carbon chain length (carbocyanation).Related Products of 55490-87-4

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Heterocyclic studies. Part XXXIX. Ring cleavage of some pyrimidine derivatives in alkali was written by Clark, Jim;Parvizi, Bahman;Colman, Robert. And the article was included in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) in 1976.Application In Synthesis of 4-Amino-6-chloropyrimidine-5-carbonitrile This article mentions the following:

4-(Substituted amino)-6-chloropyrimidines bearing a mesomeric electron-withdrawing substituent such as NO2, CN, CHO, or Ac at position 5 were cleaved by dilute NaOH at room temperature to give tetra-substituted alkenes. Thus I (0.01 mol. equivalent), H2O (20-30ml), and 2N NaOH (10ml), together with EtOH to aid partial dissolution, were stirred at ∼25° for 18-72 hr to give 98% H2NC(NHCH2Ph):C(CHO)CN. Unlike acid-catalyzed attacks on similar pyrimidines, the course of these basic reactions was not strongly influenced by steric interference between 4(6)- and 5-substituents. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Application In Synthesis of 4-Amino-6-chloropyrimidine-5-carbonitrile).

4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) 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.Application In Synthesis of 4-Amino-6-chloropyrimidine-5-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Antioxidant-based inhibitors of leukotriene biosynthesis. The discovery of 6-[1-[2-(hydroxymethyl)phenyl]-1-propen-3-yl]-2,3-dihydro-5-benzofuranol, a potent topical antiinflammatory agent was written by Hammond, Milton L.;Zambias, Robert A.;Chang, Michael N.;Jensen, Norman P.;McDonald, John;Thompson, Kathryn;Boulton, David A.;Kopka, Ihor E.;Hand, Karen M.. And the article was included in Journal of Medicinal Chemistry in 1990.Synthetic Route of C5H2N2O2S This article mentions the following:

The leukotrienes, metabolites of arachidonic acid produced through the action of the enzyme 5-lipoxygenase, are important mediators of immediate hypersensitivity and inflammation. Among the variety of diseases in which the leukotrienes may play a symptomatic or causative role is the dermatol. condition psoriasis, a chronic proliferative disease of the skin. This study reports the synthesis and comparative biol. activities of various ortho-substituted phenols including 4-methoxyphenols, 6-hydroxy-1,2,3,4-tetrahydrobenzopyrans, 2,3-dihydro-5-benzofuranols, and 5-benzofuranols. The phenols prepared in this study were evaluated for their ability to inhibit the production of leukotriene B₄ (LTB₄) in isolated human polymorphonuclear leukocytes (PMNs) and to inhibit a topical inflammatory response in the topical mouse ear (TME) model. In the former case, when the log IC₅₀ was plotted vs. the log of the octanol/water partition coefficient (log P), to eliminate the effect of lipophilicity, the 2,3-dihydro-5-benzofuranol ring system was more potent than the other ring systems examined throughout the range of partition coefficients studied. The ability to inhibit leukotriene production in vitro in human PMNs can be rationalized on the basis of a model that suggests that the observed inhibition is dependent on the kinetic ability of the inhibitor to reduce a radical species and on the fraction of inhibitor that is partitioned into the cell membrane. While the in vivo antiinflammatory activity as measured by the TME did not correlate with the in vitro data, it was felt that the TME represented a valuable measure of the ability of a compound to penetrate the skin to the site of an ongoing inflammatory response. The title compound I was chosen for further development. In the experiment, the researchers used many compounds, for example, 4-Nitrothiophene-2-carbonitrile (cas: 42137-24-6Synthetic Route of C5H2N2O2S).

4-Nitrothiophene-2-carbonitrile (cas: 42137-24-6) 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. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Synthetic Route of C5H2N2O2S

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Design, synthesis, biological evaluation and molecular modeling study of new thieno[2,3-d]pyrimidines with anti-proliferative activity on pancreatic cancer cell lines was written by Salem, Mohamed S. H.;Abdel Aziz, Yasmine M.;Elgawish, Mohamed S.;Said, Mohamed M.;Abouzid, Khaled A. M.. And the article was included in Bioorganic Chemistry in 2020.Safety of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile This article mentions the following:

In this study, twenty eight new compounds based on thieno[2,3-d]pyrimidine scaffold I [R = (2-methylphenyl)aminyl, diphenylaminyl, 2-naphthyloxy, etc.] and II [X = O, S; R¹ = Ph, 4-fluorophenyl, ethyl] were synthesized as anti-pancreatic cancer agents mimicking the benzofuro[3,2-d]pyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound I [R = (4-chlorophenyl)aminyl] (A) showed the highest cytotoxicity with an IC₅₀ value of 5.4μM. Furthermore, (A) showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC₅₀ value 0.155μM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quant. structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Safety 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. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.Safety of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Highly efficient conjugate reduction of α,β-unsaturated nitriles catalyzed by copper/xanthene-type bisphosphine complexes was written by Kim, Daesung;Park, Bu-Mahn;Yun, Jaesook. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2005.COA of Formula: C8H13N This article mentions the following:

α,β-Unsaturated nitriles are chemoselectively reduced to the corresponding saturated nitriles in high yields using a copper-DPEphos or Xantphos complex as catalyst in the presence of polymethylhydrosiloxane (PMHS) as the stoichiometric reducing agent and tert-butanol as additive. The use of tert-butanol as additive was key to success of this method. PMHS was used as stoichiometric reducing agent. In the experiment, the researchers used many compounds, for example, 2-Cyclohexylacetonitrile (cas: 4435-14-7COA of Formula: C8H13N).

2-Cyclohexylacetonitrile (cas: 4435-14-7) belongs to nitriles. Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. 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. COA of Formula: C8H13N

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Pyridyl Radical Cation for C-H Amination of Arenes was written by Roessler, Simon L.;Jelier, Benson J.;Tripet, Pascal F.;Shemet, Andrej;Jeschke, Gunnar;Togni, Antonio;Carreira, Erick M.. And the article was included in Angewandte Chemie, International Edition in 2019.Category: nitriles-buliding-blocks This article mentions the following:

Electron-transfer photocatalysis provides access to the elusive and unprecedented N-pyridyl radical cation from selected N-substituted pyridinium reagents. The resulting C(sp²)-H functionalization of (hetero)arenes furnishes versatile intermediates for the development of valuable aminated aryl scaffolds. Mechanistic studies that include the first spectroscopic evidence of a spin-trapped N-pyridyl radical adduct implicate SET-triggered, pseudo-mesolytic cleavage of the N-X pyridinium reagents mediated by visible light. In the experiment, the researchers used many compounds, for example, 3-Amino-4-methoxybenzonitrile (cas: 60979-25-1Category: nitriles-buliding-blocks).

3-Amino-4-methoxybenzonitrile (cas: 60979-25-1) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. 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.Category: nitriles-buliding-blocks

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Magic matrices for ionization in mass spectrometry was written by Trimpin, Sarah;Lutomski, Corinne A.;El-Baba, Tarick J.;Woodall, Daniel W.;Foley, Casey D.;Manly, Cory D.;Wang, Beixi;Liu, Chih-Wei;Harless, Bryan M.;Kumar, Ruby;Imperial, Lorelie F.;Inutan, Ellen D.. And the article was included in International Journal of Mass Spectrometry in 2015.Category: nitriles-buliding-blocks This article mentions the following:

The initial discovery that a heated inlet tube of a mass spectrometer is an ionization source producing ions from volatile, nonvolatile, small, and large mols. with charge states similar to electrospray ionization has been advanced to ionization requiring only the vacuum inherent with a mass spectrometer and a suitable matrix. This spontaneous ionization method was first applicable with the matrix 3-nitrobenzonitrile. Here we report that over 40 compounds have now been discovered that spontaneously convert mols. to gas-phase ions when exposed to sub-atm. pressure, some with remarkable sensitivity (10 fmol of protein insulin). The commonality of all matrixes is the ability to sublime, preferably near room temperature, through exposure to vacuum, and the ability to create charge separation under these conditions. The effect of vacuum, airflow, temperature (-80 to +150 °C) and pH (1-9) on the effectiveness of these newly discovered matrixes to ionize peptides and proteins is presented. Compounds with and without acidic hydrogen atoms act as matrixes and ionize specific compound classes. The new matrixes extend applications from peptides, proteins and drugs to compound classes without basic functionality such as lipids and synthetic polymers in the neg. and pos. modes. Mass resolution and ion mobility spectrometry aspects are also discussed. In the experiment, the researchers used many compounds, for example, 5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6Category: nitriles-buliding-blocks).

5-Methyl-2-nitrobenzonitrile (cas: 64113-86-6) 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. 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. Category: nitriles-buliding-blocks

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts