Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)
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چکیده
منابع مشابه
Methyl 3-(2-chlorophenyl)-2-(1H-indol-3-ylmethyl)-5-[1-(4-methoxyphenyl)-4-oxo-3-phenylazetidin-2-yl]-4-nitropyrrolidine-2-carboxylate
In the mol-ecule of the title compound, C(37)H(33)ClN(4)O(6), the four-membered β-lactam ring is essentially planar and is oriented at dihedral angles of 30.0 (1), 76.3 (1) and 30.9 (1)° with respect to the methoxy-phenyl ring, the phenyl ring and the indole unit, respectively. The pyrrolidine ring adopts a twist conformation. Intra-molecular C-H⋯Cl and C-H⋯O hydrogen bonds result in the format...
متن کاملSYNTHESIS OF 8-HYDROXY-6-METHOXY- 3-UNDECYLISOCOUMARIN AND 2-HY DROXY - 4-METHOXY-6-(2-OXOTRIDECYL) BENZOIC ACID
Straightforward conversion of (+)-6,8-dimethoxy-3,4-dihydro-3- undecylisocoumarin (3) to the title isocoumarin was carried out. Hydrolytic ring opening of (3) afforded the hydroxy acid (4) which was immediately oxidized to keto acid (5) using chromic acid, Cyclodehydration of (5) afforded the 6,8- dimethoxy-3-undecylisocoumarin (6) which on selective demethylation of 8- methoxy group furni...
متن کاملsynthesis of 8-hydroxy-6-methoxy- 3-undecylisocoumarin and 2-hy droxy - 4-methoxy-6-(2-oxotridecyl) benzoic acid
straightforward conversion of (+)-6,8-dimethoxy-3,4-dihydro-3- undecylisocoumarin (3) to the title isocoumarin was carried out. hydrolytic ring opening of (3) afforded the hydroxy acid (4) which was immediately oxidized to keto acid (5) using chromic acid, cyclodehydration of (5) afforded the 6,8- dimethoxy-3-undecylisocoumarin (6) which on selective demethylation of 8- methoxy group furnished ...
متن کامل2-Methyl-3-(2-methylphenyl)-7-nitroquinazolin-4(3H)-one
In the title methaqua-lone analogue, C(16)H(13)N(3)O(3), the 2-tolyl group is almost orthogonal [dihedral angle = 85.20 (5)°] to the fused ring system (r.m.s. deviation of fitted non-H atoms = 0.029 Å). In the crystal, twofold symmetry generates two-mol-ecule aggregates linked by C-H⋯O and π-π inter-actions [ring centroid-centroid distance = 3.4967 (6) Å].
متن کاملSynthesis and Antibacterial Evaluation of (S,Z)-4-methyl-2-(4-oxo-5- ((5-substituted phenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl) Pentanoic Acids
The resistance of antimicrobials has become a global hazard with the irrational use of antibiotics. Infection of drug-resistance bacteria seriously threatens human health. Currently there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of (S,Z)-4-methyl-2-(4-oxo-5-((5-substitutedphenylfuran-2-yl) methy...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2017
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.7b01375