- HETERO-HALO INHIBITORS OF HISTONE DEACETYLASE
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This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula I, II or any of Compounds 100-128 or any of those in Tables 2 or 3) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.
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- Exploring the 2- and 5-positions of the pyrazolo[4,3-d]pyrimidin-7-amino scaffold to target human A1 and A2A adenosine receptors
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A new series of 7-aminopyrazolo[4,3-d]pyrimidine derivatives (1-31) were synthesized to evaluate some structural modifications at the 2- and 5-positions aimed at shifting affinity towards the human (h) A2A adenosine receptor (AR) or both hA2A and hA1 ARs. The most active compounds were those featured by a 2-furyl or 5-methylfuran-2-yl moiety at position 5, combined with a benzyl or a substituted-benzyl group at position 2. Several of these derivatives (22-31) displayed nanomolar affinity for the hA2A AR (Ki = 3.62-57 nM) and slightly lower for the hA1 ARs, thus showing different degrees (3-22 fold) of hA2A versus hA1 selectivity. In particular, the 2-(2-methoxybenzyl)-5-(5-methylfuran-2-yl) derivative 25 possessed the highest hA2A and hA1 AR affinities (Ki = 3.62 nM and 18 nM, respectively) and behaved as potent antagonist at both these receptors (cAMP assays). Its 2-(2-hydroxybenzyl) analog 26 also showed a high affinity for the hA2A AR (Ki = 5.26 nM) and was 22-fold selective versus the hA1 subtype. Molecular docking investigations performed at the hA2A AR crystal structure and at a homology model of the hA1 AR allowed us to represent the hypothetical binding mode of our derivatives and to rationalize the observed SARs.
- Squarcialupi, Lucia,Falsini, Matteo,Catarzi, Daniela,Varano, Flavia,Betti, Marco,Varani, Katia,Vincenzi, Fabrizio,Dal Ben, Diego,Lambertucci, Catia,Volpini, Rosaria,Colotta, Vittoria
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p. 2794 - 2808
(2016/06/08)
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- NITROGEN CONTAINING HETEROARYL COMPOUNDS
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The invention is concerned with novel nitrogen-containing heteroaryl compounds of formula (I) wherein A1, A2, R1, R2, R3, R4, R5 and R6 are as defined in the descripti
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Page/Page column 52
(2012/01/03)
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- NITROGEN CONTAINING HETEROARYL COMPOUNDS
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The invention is concerned with novel nitrogen-containing heteroaryl compounds of formula (I) wherein A1, A2, (a), R1, R2, R3, R4, R5 and R6 are as defined in the desc
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Page/Page column 135
(2012/01/04)
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- 2-Phenylpyrazolo[4,3-d]pyrimidin-7-one as a new scaffold to obtain potent and selective human a3 adenosine receptor antagonists: new insights into the receptor-antagonist recognition
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A molecular simplification approach of previously reported 2-arylpyrazolo[3,4-c]quinolin-4-ones was applied to design 2-arylpyrazolo[4,3-d] pyrimidin-7-one derivatives as new human A3 adenosine receptor antagonists. Substituents with different
- Lenzi, Ombretta,Colotta, Vittoria,Catarzi, Daniela,Varano, Flavia,Poli, Daniela,Filacchioni, Guido,Varani, Katia,Vincenzi, Fabrizio,Borea, Pier Andrea,Paoletta, Silvia,Morizzo, Erika,Moro, Stefano
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experimental part
p. 7640 - 7652
(2010/08/03)
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- Enamines in heterocyclic synthesis: A route to 4-substituted pyrazoles and condensed pyrazoles
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The reaction of nitrile imines, generated in situ, from hydrazonoyl halides 3a-e with enamines 2a-c affords pyrazoles 8a-g. These pyrazoles have been used to prepare condensed pyrazoles.
- Hassaneen, Huwaida M. E.,Hassaneen, Hamdi M.,Elnagdi, Mohamed H.
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p. 1132 - 1136
(2007/10/03)
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