Tag: M.W=150-200

Li, Tingting published the artcileAsymmetric synthesis of α-(1-oxoisoindolin-3-yl)glycine: synthetic and mechanistic challenges, Application of 2-Formyl-4,5-dimethoxybenzonitrile, the main research area is oxoisoindolinyl glycine enantioselective synthesis crystal structure glycine Schiff base; cyanobenzaldehyde aldol reaction cyclization rearrangement conjugate addition.

We report herein that the NaOMe-catalyzed reactions between the chiral glycine Schiff base (S)-4 with 2-cyanobenzaldehyde provide for a convenient preparation of the novel α-(1-oxoisoindolin-3-yl)glycine of high pharmaceutical potential. The reactions involve at least eight synthetic steps and can mechanistically be realized only with application of Ni(II) complexes described in this study.

Chemical Communications (Cambridge, United Kingdom) published new progress about Aldol addition. 1013112-48-5 belongs to class nitriles-buliding-blocks, name is 2-Formyl-4,5-dimethoxybenzonitrile, and the molecular formula is C10H9NO3, Application of 2-Formyl-4,5-dimethoxybenzonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Dias, David M. published the artcileIs NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein-Protein Interactions?, Safety of 4-(5-Oxazolyl)benzonitrile, the main research area is NMR screening protein; NMR fragment screening; binding affinity; druggability; protein−protein interactions.

Modulation of protein-protein interactions (PPIs) with small mols. has been hampered by a lack of lucid methods capable of reliably identifying high-quality hits. In fragment screening, the low ligand efficiencies associated with PPI target sites pose significant challenges to fragment binding detection. Here, we investigate the requirements for ligand-based NMR techniques to detect rule-of-three compliant fragments that form part of known high-affinity inhibitors of the PPI between the von Hippel-Lindau protein and the alpha subunit of hypoxia-inducible factor 1 (pVHL:HIF-1α). Careful triaging allowed rescuing weak but specific binding of fragments that would otherwise escape detection at this PPI. Further structural information provided by saturation transfer difference (STD) group epitope mapping, protein-based NMR, competitive isothermal titration calorimetry (ITC), and X-ray crystallog. confirmed the binding mode of the rescued fragments. Our findings have important implications for PPI druggability assessment by fragment screening as they reveal an accessible threshold for fragment detection and validation.

ACS Medicinal Chemistry Letters published new progress about Drug screening. 87150-13-8 belongs to class nitriles-buliding-blocks, name is 4-(5-Oxazolyl)benzonitrile, and the molecular formula is C10H6N2O, Safety of 4-(5-Oxazolyl)benzonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Huang, Adrian published the artcileDiscovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic Acid (PSI-421), a P-Selectin Inhibitor with Improved Pharmacokinetic Properties and Oral Efficacy in Models of Vascular Injury, Related Products of nitriles-buliding-blocks, the main research area is quinoline preparation P selectin inhibitor SAR.

Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the α position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclin. development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.

Journal of Medicinal Chemistry published new progress about Arterial injury. 97009-67-1 belongs to class nitriles-buliding-blocks, name is 1-(4-Fluorophenyl)cyclopropanecarbonitrile, and the molecular formula is C10H8FN, Related Products of nitriles-buliding-blocks.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Van Genderen, H. published the artcileToxicological properties of the herbicide dichlobenil, 2,6-dichlorobenzonitrile, in warm-blooded animals, SDS of cas: 3336-34-3, the publication is Mededelingen Rijksfaculteit Landbouwwetenschappen, Gent (1966), 31(3), 1026-31, database is CAplus.

After oral administration of 100 mg. dichlobenil/kg. body weight, rabbits converted approx. 23% into 2,6-dichloro-3-hydroxybenzonitrile (I) and 2% into the 4-hydroxy analog (II). Rats excreted, resp., 22% and 9% of I and II. In mice the i.p. LD50 for I and II was 83 mg./kg. and 50 mg./kg., resp. The oral toxicity for mice and rabbits was very much lower. The effects of I and II were studied on the respiration of bakers’ yeast, on the ATPase induction in isolated mitochondria, on the contraction of isolated rat diaphragm, and on single beating rat heart cells in tissue culture. It was concluded that I and II, like other chlorophenols, were uncoupling agents of oxidative phosphorylation with approx. the same potency as 2,4-dinitrophenol. Liver function tests with dichlobenil showed different results for rats and rabbits. The effect on the liver of the rat seemed to be reversible, but, at a critical dose level for the rabbit, it was irreversible. It was suggested that in the rat liver cells the conjugation of the phenols to glucuronides and sulfates could keep pace with their formation.

Mededelingen Rijksfaculteit Landbouwwetenschappen, Gent published new progress about 3336-34-3. 3336-34-3 belongs to nitriles-buliding-blocks, auxiliary class Chloride,Nitrile,Benzene,Phenol, name is 2,6-Dichloro-3-hydroxybenzonitrile, and the molecular formula is C8H10S, SDS of cas: 3336-34-3.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Rastogi, R. R. published the artcileKetene SS-acetals. Part 9. Reaction of α-oxo- and α-cyano-ketene SS-acetals with cyanoacetamide: a new general method for substituted and fused 4-alkylthio-3-cyano-2(1H)-pyridones and formation of novel pyridones through base-induced rearrangements, Safety of 6-Methyl-4-(methylthio)-2-oxo-1,2-dihydropyridine-3-carbonitrile, the publication is Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1978), 549-53, database is CAplus.

Fourteen acylketene S,S-acetals RCOCR¹:C(SR²)₂ (R = aryl, pyridyl, alkyl; R¹ = H, aryl; R² = alkyl, aralkyl), on treatment with NCCH₂CONH₂ in base, gave 65-85% pyridones I. α-Cyanoacetals NCCR:C(SMe)₂ (R = CN, Ph, p-ClC₆H₄, p-MeC₆H₄) gave lower yields of the corresponding 6-aminopyridones. The method was successfully extended to cyclic ketene S,S-acetals, giving fused pyridones, benzoquinolone derivatives, and a (benzocyclohepta)pyridone derivative α-Alkyl-α-acylketene S,S-acetals with NCCH₂CONH₂ gave novel pyridones, e.g. II (R = MeSCH₂, CH₂:CH), formed by initial base induced proton migration in these acetals.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) published new progress about 57663-05-5. 57663-05-5 belongs to nitriles-buliding-blocks, auxiliary class Fused/Partially Saturated Cycles,Tetrahydropyrimidins, name is 6-Methyl-4-(methylthio)-2-oxo-1,2-dihydropyridine-3-carbonitrile, and the molecular formula is C8H8N2OS, Safety of 6-Methyl-4-(methylthio)-2-oxo-1,2-dihydropyridine-3-carbonitrile.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Dianati, Vahid published the artcileIncreasing C-Terminal Hydrophobicity Improves the Cell Permeability and Antiproliferative Activity of PACE4 Inhibitors against Prostate Cancer Cell Lines, Application of (E)-4-(2-Nitrovinyl)benzonitrile, the publication is Journal of Medicinal Chemistry (2018), 61(18), 8457-8467, database is CAplus and MEDLINE.

The serine protease, PACE4, is a proprotein convertase that plays a substantial role in malignancy of prostate cancer. Our initial selective PACE4 inhibitor (Ac-LLLLRVKR-NH₂) has evolved to the current lead compound C23 (Ac-DLeu-LLLRVK-Amba), which is active both in vitro and in vivo. By screening natural residues, except Cys, in C-terminal P1′ position, it was established that increasing hydrophobicity was improving cell permeability, which was directly translated into PCa cells antiproliferative activity. This cell antiproliferation enhancement seems independent from effect of P1′ residue on PACE4 affinity. Replacement of P1-Amba of C23 by Acpa ((S)-2-amino-3-(4-carbamimidoylphenyl)propanoic acid) followed by addition of tryptamine in P1′ resulted in compound 32 exhibiting superior PCa cells antiproliferative activity over the reference compound C23 (3-fold). This study sheds light on key factors that improve cell penetrating property and antiproliferative activity of PACE4 inhibitors.

Journal of Medicinal Chemistry published new progress about 5153-73-1. 5153-73-1 belongs to nitriles-buliding-blocks, auxiliary class Nitrile,Alkenyl,Nitro Compound,Benzene, name is (E)-4-(2-Nitrovinyl)benzonitrile, and the molecular formula is C9H6N2O2, Application of (E)-4-(2-Nitrovinyl)benzonitrile.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Lim, Ji Woong published the artcileIdentification of crizotinib derivatives as potent SHIP2 inhibitors for the treatment of Alzheimer’s disease, COA of Formula: C8H6ClN, the publication is European Journal of Medicinal Chemistry (2018), 405-422, database is CAplus and MEDLINE.

SH2 domain-containing inositol 5′-phosphatase 2 (SHIP2) is a lipid phosphatase that produces phosphatidylinositol 3,4-bisphosphate (PI(3,4)P₂) from phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P₃), and is involved in many diseases such as neurodegenerative diseases. A recent report demonstrating that SHIP2 inhibition decreased tau hyperphosphorylation induced by amyloid β and rescued memory impairment in a transgenic Alzheimer’s disease mouse model indicates SHIP2 can be a promising therapeutic target for Alzheimer’s disease. In the present study, the authors have developed novel, potent SHIP2 inhibitors by extensive structural elaboration of crizotinib discovered from a high-throughput screening. The authors’ representative compound 43 ((R)-5-(5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)pyrimidin-2-amine) potently inhibited SHIP2 activity as well as GSK3β activation in HT22 neuronal cells. It was also shown that 43 has favorable physicochem. properties, especially high brain penetration. Considering SHIP2 is one of key signal mediators for tau hyperphosphorylation, the authors’ potent SHIP2 inhibitor 43 may function as a promising lead compound for the treatment of Alzheimer’s disease.

European Journal of Medicinal Chemistry published new progress about 612-13-5. 612-13-5 belongs to nitriles-buliding-blocks, auxiliary class Organic Pigment, name is 2-(Chloromethyl)benzonitrile, and the molecular formula is C8H6ClN, COA of Formula: C8H6ClN.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Sekikawa, Tohru published the artcileCatalytic Activity of epi-Quinine-Derived 3,5-Bis(trifluoromethyl)benzamide in Asymmetric Nitro-Michael Reaction of Furanones, SDS of cas: 5153-73-1, the publication is Organic Letters (2015), 17(12), 3026-3029, database is CAplus and MEDLINE.

High catalytic activity of novel epi-quinine-derived 3,5-bis(CF₃)benzamide in the asym. nitro-Michael reaction is described. With 0.1-5 mol % loadings of this catalyst, the addition of 5-substituted 2(3-H)-furanones to a wide range of nitroalkenes involving challenging substrates, β-alkylnitroalkenes, smoothly proceeded, giving the Michael adducts e. g., I, in high yields (>90%) with excellent diastereo- and enantioselectivity (>98:2 dr, syn major; 88-98% ee). DFT calculation was carried out to account for the high catalytic activity.

Organic Letters published new progress about 5153-73-1. 5153-73-1 belongs to nitriles-buliding-blocks, auxiliary class Nitrile,Alkenyl,Nitro Compound,Benzene, name is (E)-4-(2-Nitrovinyl)benzonitrile, and the molecular formula is C30H32ClN7O2, SDS of cas: 5153-73-1.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Noe, C. R. published the artcileAmino alcohols. II: Preparation of enantiomerically pure pharmacologically active β-amino alcohols, Computed Properties of 13312-84-0, the publication is Monatshefte fuer Chemie (1995), 126(4), 481-94, database is CAplus.

A synthesis of β-amino alcs. is described starting from racemic or enantiomerically pure α-hydroxynitriles which were O-protected using enantiomerically pure acetal type protective groups. Reduction with lithium aluminum hydride yielded O-protected β-amino alcs. Whenever diastereomeric O-protected cyanohydrins could not be separated, the mixture was reduced and the resulting O-protected amino alcs. were separated Removal of the protective group using hydrogen chloride and methanol yielded enantiomerically pure β-amino alcs. or their corresponding hydrochlorides. For example, the chiral synthesis of (R)-1-amino-3-(1-naphthalenyloxy)-2-propanol and (S)-1-amino-3-(1-naphthalenyloxy)-2-propanol was accomplished via resolution of (±)-2-hydroxy-3-(1-naphthalenyloxy)propanenitrile.

Monatshefte fuer Chemie published new progress about 13312-84-0. 13312-84-0 belongs to nitriles-buliding-blocks, auxiliary class Chloride,Nitrile,Benzene,Alcohol,Benzene Compounds, name is 2-(2-Chlorophenyl)-2-hydroxyacetonitrile, and the molecular formula is C8H6ClNO, Computed Properties of 13312-84-0.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Noe, Christian R. published the artcileChiral lactols. XIII. On the determination of the absolute configuration of aromatic cyanohydrins and structurally related compounds, Quality Control of 13312-84-0, the publication is Liebigs Annalen (1995), 1353-60, database is CAplus.

Synthesis and conformational anal. of diastereomeric acetals, e.g. I, of aromatic cyanohydrins and structurally related compounds are described. Based on ¹H-NMR spectroscopic and x-ray data it is shown that the absolute configuration of such compounds can be assigned according to a method, which has been presented previously for secondary arylalkyl alcs.

Liebigs Annalen published new progress about 13312-84-0. 13312-84-0 belongs to nitriles-buliding-blocks, auxiliary class Chloride,Nitrile,Benzene,Alcohol,Benzene Compounds, name is 2-(2-Chlorophenyl)-2-hydroxyacetonitrile, and the molecular formula is C8H6ClNO, Quality Control of 13312-84-0.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts