- SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
-
The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 555
(2018/01/20)
-
- Dibenzo-epines: Effect of the basic side-chain on neuroleptic activity
-
Structure-activity relationships in a series of dibenzo[b,f][1,4]thiazepines and -oxazepines and dibenzo[b,e][1,4]diazepines having different basic substituents in the 11-position were studied with reference to their neuroleptic activity. A high degree of structure-specificity was found for the piperazinyl moiety as well as for the distances between the distal nitrogen atom of this group and the tricyclic ring system, which distances are probably of importance for receptor binding. It was shown that the N-oxides of the neuroleptic agents clotiapine, loxapine and clozapine were inactive in in vitro binding tests involving central dopaminergic receptors, and it is very likely therefore that the in vivo activity of these N-oxides in the rat is due to their enzymatic reduction to the active parent compounds. All derivatives having a basic side-chain other than N-alkylpiperazinyl were inactive neuroleptically, with the exception of the N-methyl-4-piperidyl derivative which showed relatively weak effects.
- Burki,Fischer,Hunziker,et al.
-
p. 479 - 485
(2007/10/05)
-
- Pyrazine derivatives
-
Pyrazine derivatives by the formula STR1 are disclosed. In the above formula, R1 and R2, which may be the same or different, each represents a hydrogen atom, a halogen atom, a hydroxy group, a lower alkoxy group, a phenyl lower alkoxy group, a phenoxy group, a mercapto group, a lower alkylthio group, a phenyl lower alkylthio group, a phenylthio group, an amino group, a substituted amino group, a lower alkyl group, a carbamoyl group or a sulfamoyl group; R3 represents a lower alkoxy group; R4, R5, and R6, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a phenyl lower alkyl group, or a phenyl group; and A represents a lower alkylene group; said R4 and A, said R5 and A, said R4 and R5, or said R5 and R6 may form a 5-membered or 6-membered nitrogen-containing heterocyclic ring which may further contain a hetero-atom together with nitrogen atom, and the pharmacologically acceptable non-toxic salts thereof. The compounds of this invention have a strong and selective antiematic activity and an effect of stimulating the gastric motility.
- -
-
-
- Pharmaceutical compositions and methods of inhibiting gastric acid secretion
-
Pharmaceutical compositions and methods of inhibiting gastric acid secretion by administering 1-(9-xanthenyl) amino-substituted-piperidines and pyrrolidines and new 1-(9-xanthenyl) amino-piperidine compounds.
- -
-
-