63200-97-5

Upstream product

• 43050-28-8 1-(4-methoxyphenyl)-1-cyclopentanecarboxylic acid 

Downstream Products

• 1072809-94-9 C₁₄H₁₉NO₃ 

Relevant academic research and scientific papers

EP300/CREBBP INHIBITOR

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.

Synthesis of β-, γ-, and δ-lactams via Pd(II)-catalyzed C-H activation reactions

Pd(II)-catalyzed intramolecular amination of sp2 and sp3 C-H bonds are developed using a combination of CuCl2 and AgOAc as the oxidant. The reaction protocol tolerates the presence of a double bond in the substrates. This catalytic reaction provides practical access to a wide range of β-, γ-, and δ-lactams. Copyright

CARBAMIC ACID COMPOUNDS COMPRISING AN ESTER OR KETONE LINKAGE AS HDAC INHIBITORS

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 (4-Phenylpiperidinyl)- and (4-Phenylpiperazinyl)alkyl-Spaced Esters of 1-Phenylcyclopentanecarboxylic Acids as Potent ?-Selective Compounds

A series of novel 4-phenylpiperidinyl and (4-phenylpiperazinyl)alkyl 1-1-phenylcyclopentanecarboxylates was synthesized and evaluated for affinity at ?1 and ?2 sites by inhibition of -(+)-pentazocine (PENT) and -1,3-di(2-tolyl)guanidine (DTG) binding in guinea pig brain. The phenylpiperidines were more potent ? ligands than the corresponding piperazines. Structural modifications varying the optimal spatial distance between the piperidine nitrogen and ester functions led to the identification of the propyl compound 24 (PENT Ki = 0.50 nM; DTG Ki = 1.17 nM) and the butyl derivative 32 (PENT Ki = 0.51 nM; DTG Ki = 0.69 nM) as novel high-affinity ?-selective agents. An ethylene spacer was optimum with para-substituted analogs. A notable finding was the discovery of 2-(4-phenylpiperidinyl)ethyl 1-(4-nitrophenyl)cyclopentanecarboxylate hydrochloride (15) (RLH-033), which demonstrated potent affinity for the PENT-defined ? site with a Ki of 50 pM, selectivity for ?1 over muscarinic M1 (>17600-fold), M2 (>34200-fold), dopamine D1 (>58000-fold), and D2 (>7000-fold) receptors, and inactivity at phenylcyclidine, NMDA, and opioid receptors. RLH-033 is a valuable tool which will aid further in understanding the biology of the ? recognition site. Information from this research has further defined the topography of the ? recognition site, which may provide an explanation for the diverse structures which bind with relatively high affinity.

Novel 1-Phenylcycloalkanecarboxylic Acid Derivatives Are Potent and Selective ?1 Ligands

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.