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The present invention is directed to novel substituted aminopiperidines which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved. ”

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G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.

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Hydroxyallylpyridyl derivatives exhibited a peculiar thermal behavior likely ascribed to the weak acidity of the ‘picoline-type’ hydrogen atom on the C-1 carbon of the allyl residue, leading to allyl inversion products. The unprotected alcohol reacted as ‘vinylogous picoline’ carbon nucleophile with strongly activated heterocyclic counterparts. A mechanistic rationale for this unprecedented reactivity was proposed.

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The invention relates to new dihydrothienopyrimidinesulphoxides of formula 1, as well as pharmacologically acceptable salts thereof, wherein X is SO or SO2, but preferably SO, and wherein R3 denotes an optionally substituted, mono- or bicyclic, unsaturated, partially saturated or saturated heterocycle or an optionally substituted, mono- or bicyclic heteroaryl and wherein R1 and R2 have the meanings stated in claim 1, as well as pharmaceutical compositions which contain these compounds. These new dihydrothienopyrimidinesulphoxides are suitable for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system or cancers.

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Phosphine oxide of the formula selected from the group consisting of STR1 wherein X is H, alkylthio of 1-4 carbon atoms, or STR2 Y is H, alkyl of 1-4 carbon atoms, Cl, Br, or STR3 Z is H, alkyl of 1-4 carbon atoms, or STR4 at least one of X, Y, and Z in the formula in which all three symbols appear is STR5 Q is H or Br; each of A and A’ is selected independently from H and alkyl of 1-4 carbon atoms, or A and A’ taken jointly is CH=CH–CH=CH; each of D and D’ is selected independently from H and CN, or D and D’ taken jointly is CH=CH–CH=CH; and each R is selected independently from alkyl of 1-4 carbon atoms, cycloalkyl of 5-6 carbon atoms, benzyl, phenyl, tolyl, and chlorophenyl.

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Cyclic voltammetry and controlled-potential electrolysis have been employed to examine the electrochemical behavior of some mono- and dichlorinated pyrazines, quinoxalines, and pyridazines at carbon and mercury cathodes in either acetonitrile or dimethylformamide containing a tetraalkylammonium salt. Unsubstituted pyrazine and pyridazine each exhibit a single reduction wave, whereas unsubstituted quinoxaline shows three cathodic waves. For the chlorinated compounds, an additional wave is seen for the reduction of each carbon-chlorine bond. Depending on the potential of the cathode, bulk electrolyses of dichlorinated pyrazines or quinoxalines afford either the monochlorinated or fully dechlorinated product, whereas the monochlorinated analogues undergo reduction to the dechlorinated species. Electrolyses of chlorinated pyridazines give dark colored solutions, but the products (apparently polymeric) cannot be detected or identified by means of conventional GC, GC-MS, and HPLC techniques.

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For the first time, heterogeneous osmium tetroxide catalyzed asymmetric aminohydroxylation of olefins on polymer-supported ligands have been shown to proceed with comparable rate as in the case of homogeneous conditions.

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The present invention relates to compounds that are fast dissociating dopamine 2 receptor antagonists, processes for preparing these compounds, pharmaceutical compositions comprising these compounds as an active ingredient. The compounds find utility as medicines for treating or preventing central nervous system disorders, for example schizophrenia, by exerting an antipsychotic effect without motor side effects.

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Pd-catalyzed cross-coupling reactions of 3,6-dichloropyridazine (1) with benzyl, aryl, and alkyl organozinc compounds led to selective mono-substitution of one of the chlorine atoms. The subsequent cross-coupling of the resulting monochlorides with RZnCl afforded unsymmetrical 3,6-carbon-disubstituted pyridazines.

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The present disclosure describes compounds which are Akt kinase inhibitors useful for the treatment of cancer. The compounds disclosed herein are bivalent ligands capable of binding with both the kinase enzyme ATP binding domain and the kinase enzyme substrate binding domain.

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