120737-78-2Relevant articles and documents
Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents
Blackmore, Timothy R.,Jacobson, Jonathan,Jarman, Kate E.,Lewin, Sharon R.,Nguyen, William,Purcell, Damian F.,Sabroux, Helene Jousset,Sleebs, Brad E.
, (2020/04/08)
A persistent latent reservoir of virus in CD4+ T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC50s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents.
Thiazolidine derivatives or salts thereof as an active ingredient an inhibitor Pim
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Paragraph 0657; 0659, (2018/10/19)
PROBLEM TO BE SOLVED: To provide compounds which have excellent Pim inhibitory action and are useful as pharmaceuticals.SOLUTION: A compound is a thiazolidine derivative represented by the general formula (1) in the figure, or a salt thereof. (In the formula, X represents O or S; Rrepresents a hydrogen atom or a Calkyl group; Z, Z, Z, Z, Zand Zeach independently represent CH or N; Y represents an optionally substituted, divalent Caromatic hydrocarbon group or the like; Am represents a disubstituted amino group, or an optionally substituted, nitrogen-containing saturated heterocyclic group; and Rand Reach independently represent a hydrogen atom, a halogen atom, an alkyl group or the like.)
METHODS OF USING DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE)POLYMERASE (PARP)
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Page/Page column 167, (2011/11/01)
Provided herein are methods of treating cancer comprising administering a topoisomerase inhibitor, temozolomide, or a platin in combination with a Compound of Formula (I) or Formula (II), where the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein.
DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
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Page/Page column 86, (2010/03/02)
A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
1,4-DISUBSTITUTED PIPERAZINE AND 1,4-DISUBSTITUTED AZEPANE AS 11 -BETA-HYDROXYSTEROID DEHYDROGENASE 1 INHIBITORS
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Page/Page column 31, (2010/11/29)
Compounds of formula (I): wherein variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are described.
Process for the preparation of quinoline antibacterial compounds
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, (2008/06/13)
A process for preparing substituted 7-(piperazin-1-yl)-4-oxo-1,4-dihydro-3-quinoline carboxylic acid derivative antibacterial agents by reacting a carbamate protected piperazine derivative with a 7-halo-4-oxo-1,4-dihydro-quinoline carboxylic acid derivati
N-aryl-piperazinealkanamides useful for improving sleep
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, (2008/06/13)
A method of improving sleep in warm-blooded animals suffering from sleep disorders, which method comprises the administration of particular N-aryl-piperazinealkanamide derivatives and compositions containing the same. Novel N-aryl-piperazinealkanamide derivatives.