150807-88-8

The Wnt signaling pathway is a critical developmental pathway which operates through control of cellular functions such as proliferation and differentiation. Aberrant Wnt signaling has been linked to the formation and metastasis of tumors. Porcupine, a member of the membrane-bound O-acyltransferase family of proteins, is an important component of the Wnt pathway. Porcupine catalyzes the palmitoylation of Wnt proteins, a process needed for their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from a known porcupine inhibitor class. The leading compound 59 demonstrated subnanomolar inhibition of Wnt signaling in a paracrine cellular assay. Compound 59 also showed excellent chemical, plasma and liver microsomal stabilities. Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.

The present invention relates to compositions and methods for modulating the Wnt signaling pathway, using compounds having Formula (1) and (3): wherein A, B, Y and Z all represent rings, and R1, R2, R3 are as defined herein.

The present invention relates to compounds of formulae 1 and 2 and methods for modulating the Wnt signaling pathway using these compounds, wherein A1, A2, B, Y and Z all represent rings.

The object of the invention is to provide new compounds which can be used for the treatment of diseases, in particular cardiovascular and haematological diseases. The present invention describes compounds which act as specific HIF-prolyl-4-hydroxylase inhibitors and which, because of this specific in vivo action mechanism, induce HIF target genes, such as erythropoietin, and the thus produced biological processes, such as erythropoiesis, after parenteral or oral administration. The present invention relates to compounds having the general formula (I), in which A stands for CH or N, R1 stands for a substituent selected from the group formed by (C1-C6)-alkyl, trifluoromethyl, halogen, cyano, nitro, hydroxy, (C1-C6)-alkoxy, amino, (C1-C6)-alkoxycarbonyl, hydroxycarbonyl and C(=O)-NH-R4; R2 stands for a substituent selected from the group formed by halogen, cyano, nitro, (C1-C6)-alkyl, trifluoromethyl, hydroxy, (C1-C6)-alkoxy, trifluoromethoxy, amino, hydroxycarbonyl and C(=O)-NH-R8; m equals 0, 1 or 2; n equals 0, 1, 2 or 3, it being possible for these meanings to be the same or different when R1 or R2 occurs multiple times; and R3 stands for hydrogen, (C1-C6)-alkyl or (C3-C7)-cycloalkyl. The invention also relates to the salts, solvates, and salt solvates of these compounds.

Imidacloprid is the first chloronicotinyl insecticide and is currently the largest-selling insecticide worldwide. As a project to find its variants of different insecticidal spectra, derivatives substituted with methyl, trifluoromethyl, and methoxy-carbonyl at the fifth position on the pyridine ring of imidacloprid were prepared. Copyright Taylor & Francis Group, LLC.

Disclosed are preferred processes for preparing a 2-halo-5-halomethylpyridine compound. The preferred processes involve cyclocondensing a 2-halo-2-halomethyl aldehyde or ketone of the formula (II) STR1 to form a 2-halo-2-halomethylpyridine compound of the formula (III) STR2 wherein X is Cl or Br, Y is a cyano group or an aminocarbonyl group, and R, R1, R2 and R3 are, independently, H or an organic radical which does not interfere with the cyclocondensation.