Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase ...

In this research, it was presented a simple and efficient method for one-pot synthesis of 2-arylbenzoxazoles which were directly synthesized from o-aminophenol and aromatic or heteroaromatic aldehydes catalyzed by MWCNTs supported KCN in DMF media under ultrasound irradiation. MWCNTs supported K...

Herein, we have carried out a structural optimization campaign to discover the novel anti-tumor agents with our previously screened YQY-26 as the hit compound. A library of thirty-seven 6-amide-2-aryl benzoxazole/benzimidazole derivatives has been designed and synthesized based on the highly con...

Enantiopure [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol 5a and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]-(diphenyl)methanol 5b, new β-amino alcohols based on l-pipecolinic acid (homoproline), have been prepared straightforwardly from rac-alaninol and rac-2-amino-1,1-diphenylpropan...

The reactions of (aryl)(chloro)methyl p-tolyl sulfoxides 2 with tetrasulfur tetranitride (S4N4) in p-dioxane at reflux gave 3,5-diaryl-1,2,4,6-thiatriazine 1-oxides, 3,5-diaryl-1,2,4-thiadiazoles, and 1-amino-3,5-diaryl-1,2,4,6-thiatriazine 1-oxides. For the first time, the structures of 3,5-dia...

Through a structure-guided rational drug design approach, we have discovered a highly selective inhibitor compound 40 (JSH-150), which exhibited an IC50 of 1 nM against CDK9 kinase in the biochemical assay and achieved around 300–10000-fold selectivity over other CDK kinase family members. In a...

A series of novel N-(pyrimidin-4-yl)thiazol-2-amine derivatives have been synthesized and evaluated as glucokinase (GK) activators. Ethyl 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl-amino)thiazole-5-carboxylate was found to be a potent dual-acting hypoglycemic agent activating...

New 2-[2-(phenylamino)thiazol-4-yl]ethanamine and 2-(2-benzhydrylthiazol-4-yl)ethanamine derivatives were prepared and tested in vitro as H1 receptor antagonists. The compounds with 2-phenylamino substitution with meta-halide substituents at the phenyl ring, showed weak H1-antagonistic activity ...

A series of 10 new N-phenyl-4-(4-(thiazol-2-yl)-phenyl)-thiazol-2-amine derivatives (3a–j) and 4 new 5-(2-(phenylamino)-thiazol-4-yl)-benzamide ethers (3′a–d) were synthesized from 4-(2-phenylamino)-thiazol-4-yl)-benzothioamide and 2-hydroxy-5-(2-(phenylamino)-thiazol-4-yl)-benzamide with sev...

A series of 1,4-substituted arylalkyl piperazine derivatives were synthesized and studied with the aim to obtain potent P-gp-dependent multidrug-resistant (MDR) reversers. The new compounds were designed on the basis of the structures of our previous arylamine ester derivatives endowed with high...

New analogues of the recently published compound DDD107498 were prepared. Their activities were examined in vitro against the chloroquine-sensitive NF54 strain. The most active were also tested against the multiresistant K1 strain of Plasmodium falciparum. A couple of the newly synthesized compo...

The synthesis of some aroylisothiosemicarbazides was accomplished and their biological activity against bacteria, fungi, and mycobacteria was investigated. Different synthetic pathways were followed according to the kind of substituents that were introduced on both the aroyl ring and the sulfur ...

Preptin, a 34-amino acid residue peptide hormone is co-secreted with insulin from the β-pancreatic cells and is active in fuel metabolism. We have previously established that a shorter fragment of preptin, namely preptin-(1–16), stimulates bone growth by proliferation and increasing the surviv...

A thiolprotease from rat brain membranes was shown to convert synthetic dynorphin B-29 (Dyn B-29, “leumorphin”) to the tridecapeptide dynorphin B (Dyn B, “rimorphin”). This represents a “single-arginine cleavage” between threonine-13 and arginine-14 of the substrate. The dynorphin converti...

Leumorphin and rimorphin (dynorphin B) were nearly equipotent in inhibiting the contraction of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum and the rabbit vas deferens. Leumorphin had long duration of action in vitro after wash-out, whereas the duration of action ...

Using synthetic leumorphin, we obtained antisera for leumorphin and set up two radioimmunoassays (RIAs) with different specificities. Gel exclusion chromatography coupled with the two RIAs showed the existence of a considerable amount of leumorphin-like peptide in water extracts from porcine neu...

Leumorphin, an opioid peptide whose functions are unknown, is found in mammalian brain and pituitary and stimulates lordosis behavior in estrogen-treated female rats. To elucidate the role of leumorphin in the physiological control of female sexual behavior, the levels of immunoreactive (ir) leu...

Porcine leumorphin, a putative opioid peptide corresponding to amino acid residues 228–256 of preproenkephalin B has been demonstrated to exist in the porcine neurointermediate pituitary. A recent study on the sequence analysis of genomic DNA of human preproenkephalin B has shown that human leu...

The regional distribution of human leumorphin (HL)-like immunoreactivity (HL-LI) in monkey (Macaca fuscata) spinal cord and dorsal root ganglia was investigated by peroxidase-anti-peroxidase immunocytochemistry using specific antiserum. HL-LI-positive fibers and terminals were distributed densel...

The opioid activity and opioid receptor type specificity of synthetic human leumorphin were studied in vitro. Human leumorphin inhibited the contraction of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum and was similar in opioid potency to porcine leumorphin. This a...