5383-83-5Relevant academic research and scientific papers
Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
, p. 17887 - 17896 (2020/08/19)
An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
Quinazolinyl carboxylic ester derivative containing isoindolone group and application thereof
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Paragraph 0056-0058; 0078-0080, (2021/01/04)
The invention discloses a quinazolinyl carboxylic ester derivative containing an isoindolone group, and the derivative has a structural general formula shown as the specification, wherein R is aryl substituted alkyl, aryl substituted cyclolky or biaryl. According to the invention, the novel isoindolone group-containing quinazolinyl carboxylic ester derivative is synthesized, can effectively inhibit the growth of antibiotic-sensitive or drug-resistant bacteria, and has a new action mechanism.
Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms. Part II: Furoxan derivatives
Dos Santos, Jean Leandro,Lanaro, Carolina,Chelucci, Rafael Consolin,Gambero, Sheley,Bosquesi, Priscila Longhin,Reis, Juliana Santana,Lima, Lídia Moreira,Cerecetto, Hugo,González, Mercedes,Costa, Fernando Ferreira,Chung, Man Chin
, p. 7583 - 7592 (2012/11/07)
Phthalimide derivatives containing furoxanyl subunits as nitric oxide (NO)-donors (3a-g) were designed, synthesized, and evaluated in vitro and in vivo for their potential uses in the oral treatment of sickle cell disease symptoms. All compounds (3a-g) demonstrated NO-donor properties at different levels. Moreover, compounds 3b and 3c demonstrated analgesic activity. Compound 3b was determined to be a promising drug candidate for the aforementioned uses, and it was further evaluated in K562 culture cells to determine its ability to increase levels of γ-globin expression. After 96 h at 5 μM, compound 3b was able to induce γ-globin expression by nearly three times. Mutagenic studies using micronucleus tests in peripheral blood cells of mice demonstrated that compound 3b reduces the mutagenic profile as compared with hydroxyurea. Compound 3b has emerged as a new leading drug candidate with multiple beneficial effects for the treatment of sickle cell disease symptoms and provides an alternative to hydroxyurea treatment.
Functionalised acyl ferrocenes: Crystal and molecular structures of 4-aminobenzoylferrocene, 4-hydroxybenzoylferrocene and 1,1′-bis(4-hydroxybenzoyl)ferrocene
Benyei, Attila C.,Glidewell, Christopher,Lightfoot, Philip,Royles, Brodyck J.L.,Smith, David M.
, p. 177 - 186 (2007/10/03)
Improved methods of synthesis are reported for FcCOC6H4F-4 1a, FcCOC6H4OMe-4 1b and Fcd(COC6H4OMe-4)2 2b [Fc = (C5H5)Fe(C5H4); Fcd = (C5H4)Fe(C5H4)]: demethylation of 1b and 2b, using AlCl3 in 1,1,2-trichloroethane, yields FcCOC6H4OH 1f and Fcd(COC6H4OH)2 2f respectively. Acylation of ferrocene using 4-phthalimidobenzoyl chloride yields 4-(phthalimidobenzoyl)ferrocene 1c, hydrazinolysis of which yields FcCOC6H4NH2-4 1d. Crystal structures are reported for 1d, 1f and 2f: in 1d and 1f the molecules are linked into spiral chains by means of N-H ... O=C and O-H ... O=C hydrogen bonds respectively; in 2f the O-H ... O=C hydrogen bonds link the centrosymmetric molecules into continuous two-dimensional nets, two independent sets of which are interwoven.
Synthesis and neuropeptide Y Y1 receptor antagonistic activity of N,N-disubstituted ω-guanidino- and ω-aminoalkanoic acid amides
Mueller, Manfred,Knieps, Sebastian,Gessele, Karin,Dove, Stefan,Bernhardt, Guenther,Buschauer, Armin
, p. 333 - 342 (2007/10/03)
Patent arpromidine-type histamine H2 receptor agonists such as BU-E-76 (He 90481) were among the first non-peptides reported to display weak neuropeptide Y (NPY) Y1 receptor antagonist activity. In search of new chemical leads for the development of more potent NPY antagonists, a series of N,N-disubstituted ω-guanidino and ω-aminoalkanoic acid amides were synthesized on the basis of structure-activity relationships and molecular modeling studies of arpromidine and related imidazolylpropylguanidines. In one group of compounds the imidazole ring was retained whereas in the second group it was replaced with a phenol group representing a putative mimic of Tyr36 in NPY. Although the substitution patterns have not yet been optimized, the title compounds are NPY Y1 antagonists in human erythroleukemia (HEL) cells (Ca2+ assay) achieving pK(B) values in the range of 6.3-6.6. For representative new substances tested in the isolated guinea pig right atrium histamine H2 receptor agonism could not be found. In the N-(diphenylalkyl)amide series, compounds with a trimethylene chain were more active Y1 antagonists than the ethylene homologs. Concerning the spacer in the ω-amino or ω-guanidinoalkanoyl portion, the best activity was found in compounds with a four- or five-membered alkyl chain or a 1,4-cyclohexylene group. Surprisingly, in contrast to the phenol series, in the imidazole series the compounds with a side chain amino group turned out to be considerably mere potent than the corresponding strongly basic guanidines. Thus, the structure-activity relationships appear to be different for the diphenylalkylamide NPY antagonists with one or two basic groups.
Synthesis of a Tetrafluoro-Substituted Aryl Azide and Its Protio Analogue as Photoaffinity Labeling Reagents for the Estrogen Receptor
Pinney, Kevin G.,Katzenellenbogen, John A.
, p. 3125 - 3133 (2007/10/02)
A tetrafluoro-substituted aryl azide 1 and its protio analogue 2, both photoaffinity labeling reagents for the estrogen receptor, have been prepared by direct coupling of the appropriately substituted 4-azidobenzoyl chloride with the electron rich C-3 of 6-methoxy-2-(4-methoxyphenyl)benzothiophene 3.This represents a rare example of aryl azide stability under Friedel-Crafts acylation conditions.Alternatively, the protio analogue 2 can also be prepared with the azide functionality masked as a phthaloyl-protected arylamine, and the tetrafluoro analogue 1, by direct displacement of a pentafluoroaryl derivative 20 with NaN3.Solution photolysis of tetrafluoro-substituted aryl azide (bis-methyl ether) 15 and its protio analogue 16 in toluene at 30 deg C results in relatively high yields of products derived from C-H insertion.Both azides 1 and 2 demonstrate favorable relative binding affinity (RBA) (1 = 10percent, 2 = 66percent, estradiol = 100percent) and photoinactivation efficiency (1 = 43percent, 2 = 55percent at 30 min) for the estrogen receptor (ER).The synthesis of both azides has been modified to accommodate a palladium-catalyzed tritium gas hydrogenolysis of an iodoaryl precursor at a late stage in the synthetic sequence, as will be needed to prepare them in radiolabeled form, and this procedure has been verified dy deuteration.This pair of compounds will allow a detailed evaluation of the role that fluorine substitution plays in the photochemistry and photocovalent attachment behavior of aryl azides in a complex biochemical system, the estrogen receptor.The radiosynthesis and further biochemical results will be presented elsewhere.
