Efficient syntheses of the 3-, 9-, 10-, and 11-phenol isomers of dibenz[a,c]anthracene (DBa,cA) and 2,3-dihydroxy-DBa,cA are described. Bromination of DBa,cA with bromine in CH2Cl2 gave 10-bromo-DBa,cA and not 9-bromo-DBa,cA predicted theoretically. On the other hand, bromination of DBa,cA with ...

4,5-Diaryl-1,2,3-benzenetricarboxylates were prepared by cycloaddition of 4-hydroxycyclo-2-penten-1-one-2-carboxylates with dimethyl acetylenedicarboxylate.

Morphine is widely used for the treatment of severe pain. This analgesic effect is mediated principally by the activation of μ-opioid receptors (MOR). However, prolonged activation of MOR also results in tolerance, dependence, addiction, constipation, nausea, sedation, and respiratory depressio...

Two series of arylpiperazinyl–alkyl quinoline-, isoquinoline-, naphthalene-sulfonamides with flexible (13–26) and semi-rigid (33–36) alkylene spacer were synthesized and evaluated for 5-HT1A, 5-HT2A, 5-HT6, 5-HT7 and selected compounds for D2, D3, D4 receptors. The compounds with a mixed 5-HT...

FLT3 inhibitors have been explored as a viable therapy for acute myeloid leukemia (AML). However, the clinical outcomes of these FLT3 inhibitors were underwhelming except AC220. Therefore, the development of novel FLT3 inhibitors with high potency against both FLT3-WT and FLT3-ITD mutants are st...

Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cy...

With an ynone as accepting group, imidazo[1, 2-a] pyridine as dye, a new sensor for hydrazine was investigated. The carbonyl group, which serves as a fluorescent quenching group in the sensor, can react with hydrazine to form a pyrazole, thus allowing fluorescent turn-on type signaling. With thi...

The tyrosine kinase inhibitor ponatinib is extensively metabolized in the body, and consequently the development of specific immunoassays for pharmacokinetic studies and therapeutic drug monitoring of ponatinib is challenging. If two antibodies simultaneously recognize the entire structure of po...

Non-alcoholic fatty liver disease is manifested by hepatic accumulation of triglycerides (TG) and is commonly associated with metabolic syndrome. The isoprenoid farnesol (FOH) modulates lipid metabolism and reduces hepatic TG content in rodents. This effect involves activation of at least two nu...

The synthesis of new 2-(pyrrolidine-3-yl)acetic acid derivatives as cyclic γ-aminobutyric acid analogues, which are additionally substituted at the 4-position, is reported. A de Mayo reaction, i.e. a combination of an intermolecular [2+2]-photocycloaddition of 1,3-dioxinones with N-protected 3-...

Cycloaddition between (+) or (−)-menthone-derived nitrones and N-benzyl-3-pyrroline afforded enantiopure spiro-fused heterocycles. The reaction occurred enantio- and diastereo-selectively on the less hindered side of the nitrone, the 3-pyrroline N-benzyl group being oriented outwards, thus contr...

A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib’s core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyr...

Publisher SummaryThis chapter discusses various aspects of chloromethyl ketone derivatives of fatty acids. α-Haloketones are very susceptible to nucleophilic attack, which makes this functional group ideally suited for the design of specific enzyme active-site-directed inhibitors. Classic examp...

Oxidation products of phytoplanktonic monounsaturated fatty acids have been detected in particulate matter and recent sediment samples collected at the SOFI station (Gulf of Fos, Mediterranean Sea). The fluxes of these compounds are not negligible and correspond to 0.14–0.03% of the total organ...

Efficient three-step syntheses of α-chloro keto acids 1a-c from ω-alkenoic acids 2 and ω-alkenyl alcohols 3 are described, proceeding via epoxidation/chloride-mediated epoxide ring opening/Jones oxidation protocols.

A series of cycloalkyl-substituted oxo-alkanedicarboxylic acids have been prepared by the TosMIC methodology departing from haloalkyl-substituted cycloalkylcarboxylic esters. cyclopropyl derivatives showed IC50 activity in the 0.3–1.0 μM range on the de novo incorporation of radiolabeled aceta...

α-Ketol of octadecadienoic acid (KODA, 1) has been suggested to play a role in the photoperiod-regulated flowering in Pharbitis nil. The level of 1 in cotyledons is temporarily controlled during short-day conditions. The biosynthesis of 1 is well studied in plants; however, its in vivo conversi...

A strategy is described to locate the carbonyl position in oxofatty acids by utilizing charge-remote fragmentations of various molecular ions that are desorbed by fast atom bombardment (FAB). Oxofatty acids were cationized with alkali metal ions (Li+, Na+, K+, Rb+, and Cs+) to form [M+2Met − H]+...

Positional isomers of aliphatic keto carboxylic acids (C6C15) in marine aerosol samples collected in the North Pacific Ocean have been identified by using capillary gas chromatography—mass spectrometry (GC—MS). The keto group was determined to be in the γ- to (ω — 1)-position. These keto ...

Current study is based on the sequential conversion of indolyl butanoic acid (1) into ethyl indolyl butanoate (2), indolyl butanohydrazide (3), and 1,3,4-oxadiazole-2-thiol analogs (4) by adopting chemical transformations. In a parallel series of reactions, 2-bromo-N-phenyl/arylacetamides (7a-l)...