Since the oversecretion of protein kinases is indicative of multiple human diseases, the screening of their activities is quite important to clinical diagnosis and targeted therapy. In this work, an ultrasensitive peptide-based electrochemical biosensor was presented for the detection of protein...

Compounds simultaneously inhibiting two targets that are involved in the progression of the same complex disease may exhibit additive or even synergistic therapeutic effects. Here we unveil 2,4,5-trisubstituted imidazoles as dual inhibitors of p38α mitogen-activated protein kinase and glycogen ...

All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are the 2-iso-oxacephem analogues of Thienamycin, have been synthesized. (αR,6R,7R)- and (αS,6S,7S)-7-(1-hydroxyethyl)-3-methyl-2-iso-oxacephem-4-carboxylic acids have been prepared starting from l- an...

Rats were treated intermittently or continuously with the dopamine D1 receptor antagonist NNC-756 for 15 weeks. Two weeks after withdrawal they were challenged with the dopamine D1 receptor agonist SK&F 38393, either alone or after pretreatment with NNC-756. Neither treatment regimen resulted in...

Dopamine D1 receptor blockade does not appear to be a prerequisite for antipsychotic activity since many clinically effective antipsychotics have little or no affinity for this receptor subtype. Clozapine, however, which has minimal liability for extrapyramidal symptoms, possesses affinities of ...

NNC 22-0010 is a new dopamine antagonist with a high affinity and selectivity for D1 receptors in vitro. NNC 22-0010 has both an N-methyl group and a bromine, which allows radiolabelling with either 11C or 76Br. We labelled [11C]NNC 22-0010 by N-methylation of the free base of the secondary amin...

NNC 22-0215 has been found to be a metabolically stable dopamine D1 antagonist with high affinity and selectivity for D1 receptors in vitro. We prepared [11C]NNC 22-0215 with a specific radioactivity of about 50 GBq/μmol at time of administration. In PET experiments with [11C]NNC 22-0215 there ...

The ability of dopamine D2, mixed D1/D2 and selective D1 receptor antagonists, including NNC-112, NNC-687, NNC-756, to inhibit the in vivo binding of [3H]SCH 23390 or [3H]raclopride to dopamine receptors was studied in mice and rats. Furthermore, the dopamine-antagonistic effects of these drugs ...

NNC 687 and NNC 756 [(+)-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-8-nitro-2,3,4,5-tetrahydro-1H-3-benzazepine and (+)-8-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine] are two new potent dopamine D-1 receptor antagonists. [11C]NNC 687 and [1...

This paper details the first study of the effects of dopamine D1 receptor antagonism on the regulation of human sleep EEG (electroencephalogram). The investigational drug NNC-687 (NNC 01-0687/CEE 03-310) was administered to 20 healthy young men in doses of 5, 10, and 15 mg in a double blinded, p...

The neurochemical properties of three novel benzazepine derivatives NNC-112, NNC-687 and NNC-756 were assessed. These compounds inhibited dopamine D1 receptor binding in vitro with low nanomolar to picomolar dissociation constants whereas those for the D2 receptor were in the micromolar range. C...

Selective N-type Voltage Activated Calcium Channel (VACC) blockers have shown utility in several models of stroke and pain. In the process of searching for small molecules as N-type calcium channel blockers, we have identified a series of N,N-dialkylpeptidylamines (e.g., PD 175069) with potent f...

We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covalent binding in microsome preparations.

The first syntheses of (2S,3R)- and (2S,3S)-3-chloroleucine (3-chloro-d-leucines 1 and 2) have been achieved from d-3-hydroxyleucine and allo-d-3-hydroxyleucine, respectively, through the formation of the corresponding N-Cbz β-lactones, followed by a ring opening promoted by lithium chloride an...

The magnesium amides Mg(NHi-C3H7)2; Mg(N(C2H5)2)2 and Mg(NC5H10)2 have been prepared by direct synthesis from magnesium and i-C3H7NH2, (C2H5)2NH or C5H10NH, respectively, at high temperature and under a pressure of hydrogen. When an excess of Mg was used MgH2 was isolated, suggesting that magnes...

Imines derived from O-protected (S)-glyceraldehyde are valuable intermediates in the synthesis of different kinds of amino acids. We have developed a highly convergent and stereoselective method to obtain (2S,3S)-N-tert-butoxycarbonyl-1-phenyl-3,4-epoxy-2-butylamine and (2S,4R)-N-tert-butoxycarb...

A procedure for the separation of diastereomeric (+)-1-hydroxy-2-butylamides of d- and l-lysergic and d- and l-isolysergic acids by thin-layer chromatography has been developed. By using aqueous solutions of imidazole as one of the components of the solvent system, greater differences were found...

N-Triflouroacetyl (TFAc)-d,l-aspartic acid (Asp) isopropyl ester and N,O-TFAc-l-hydroxyproline (Hpr) isopropyl ester, which give overlapping peaks when a single chiral capillary column is used, were separated with a cross-linked polycyanoethyl vinyl siloxane-l-Val-tert.-butylamide capillary colu...

The macroscopic and microscopic protonations of DTPA-GlucA2 (DTPA-bis(glucamide)) have been investigated using potentiometry, 1H and 13C NMR. The protonation behavior appears to be similar to that of the corresponding bis(alkylamides), showing that it is not affected by the presence of the polyh...

This study shows that the cyclization of l-DMDP thioureas to bicyclic l-DMDP isothioureas improved α-l-rhamnosidase inhibition which was further enhanced by increasing the length of the alkyl chain. The addition of a long alkyl chain, such as decyl or dodecyl, to the nitrogen led to the product...