63200-97-5Relevant articles and documents
EP300/CREBBP INHIBITOR
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Paragraph 0514; 0516, (2020/05/30)
The present invention provides a compound having excellent histone acetyltransferase inhibitory activity against EP300 and/or CREBBP, or a pharmacologically acceptable salt thereof. The compound is represented by the following formula (1) or a pharmacologically acceptable salt thereof: wherein ring Q1, ring Q2, R1, R2, R3 and R4 respectively have the same meanings as defined in the specification.
CARBAMIC ACID COMPOUNDS COMPRISING AN ESTER OR KETONE LINKAGE AS HDAC INHIBITORS
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Page 150; 81, (2008/06/13)
This invention pertains to certain carbamic acid compounds of the formula (I), which inhibit HDAC (histone deacetylase) activity: wherein: J is a linking functional group and is independently: -O-C(=O)- or -C(=O)-O- or - C(=O)-; Cy is a cyclyl group and is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is a cyclyl leader group, and is independently a divalent bidentate group obtained by removing two hydrogen atoms from a ring carbon atom of a saturated monocyclic hydrocarbon having from 4 to 7 ring atoms, or by removing two hydrogen atoms from a ring carbon atom of saturated monocyclic heterocyclic compound having from 4 to 7 ring atoms including 1 nitrogen ring atom or 1 oxygen ring atom; and is optionally substituted; Q2 is an acid leader group, and is independently: C1-8alkylene; and is optionally substituted; or: Q2 is an acid leader group, and is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC,and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.
Novel 1-Phenylcycloalkanecarboxylic Acid Derivatives Are Potent and Selective ?1 Ligands
Calderon, Silvia N.,Izenwasser, Sari,Heller, Brett,Gutkind, J. Silvio,Mattson, Mariena V.,et al.
, p. 2285 - 2291 (2007/10/02)
Carbetapentane (1, 2-ethyl 1-phenyl-1-cyclopentanecarboxylate) binds with high affinity to ? sites and is a potent antitussive, anticonvulsant, and spasmolytic agent.However, carbetapentane interacts at muscarinic binding sites as well, and it is not clear whether either of these receptor systems is involved in the mechanism(s) of action(s) of this drug.In an attempt to determine whether these psychoactivities can be attributed to interaction at ? sites, a series of carbetapentane analogs were prepared.Phenyl ring substitution; contraction expansion, and replacement with a methyl group of the cyclopentyl ring; replacement of the carboxylate function with an amide, methyl ether, and methylamine; and replacement of the N,N-diethyl substituent with a morpholino or piperidino moiety were investigated.All of these novel analogs were evaluated for binding to ?1 and ?2 sites, and comparison of binding at muscarinic m1 and m2 and PCP (1-(1-phenylcyclohexyl)piperidine) receptors was performed.All of the compounds were selective for ?1 over ?2 sites, with the three most selective analogs being compounds 34 (65-fold), 35 (78-fold), and 39 (51-fold).None of the compounds were active at PCP sites, and chemical modification including (1) replacing the ester function, (2) replacing the cyclopentyl ring with a smaller ring system (cyclopropyl) or a methyl group, and (3) replacing the diethylamino moiety with a morpholino group resulted in >220-fold selectivity over muscarinic receptor binding.Therefore, several of these novel compounds are potent, ?1-selective ligands which can now be investigated as potential antitussive, anticonvulsant, and antiischemic agents.These studies may reveal whether ?1 sites play a role in the pharmacological actions of these drugs.
