59756-83-1

Upstream product

• 130604-43-2 ethyl 3-(benzyloxyphenyl)acetate 
• 22446-38-4 ethyl 3-hydroxyphenylacetate 
• 100-39-0 benzyl bromide 
• 79-37-8 oxalyl dichloride 
• 1860-58-8 3-benzyloxyphenylacetic acid 
• 621-37-4 m-hydroxyphenylacetic acid 

Downstream Products

• 295320-27-3 N-(2,4-dichlorophenyl)-2-[3-(phenylmethoxy)phenyl}acetamide 
• 151841-47-3 (R)-6,7-dimethoxy-1-(3-hydroxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1316258-58-8 (S)-2,3-dimethoxy-9-hydroxyberbine 
• 1316259-19-4 (R)-1-(3-hydroxybenzyl)-6,7-methylenedioxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1316259-17-2 (S)-9-hydroxy-2,3-methylenedioxyberbine 
• 1316259-11-6 (R)-1-(3-hydroxybenzyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1316259-10-5 (S)-9-hydroxy-3-methoxyberbine 
• 1316259-15-0 (R)-1-(3-hydroxybenzyl)-2-methyl-6,7,8-trimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 1316259-14-9 (S)-9-hydroxy-1,2,3-trimethoxyberbine 
• 1316259-22-9 (R)-1-(3-hydroxybenzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1719-33-1 1-(3-hydroxybenzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1871-08-5 1-(3-benzyloxybenzyl)-7-benzyloxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1213254-30-8 (R)-1-(4-(1-(2-(3-(cyclopropylmethoxy)phenyl)propyl)-1H-1,2,3-triazol-5-yl)butyl)pyrimidine-2,4(1H,3H)-dione 
• 1213255-07-2 (S)-1-(4-(1-(2-(3-(cyclopropylmethoxy)phenyl)propyl)-1H-1,2,3-triazol-5-yl)butyl)pyrimidine-2,4(1H,3H)-dione 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of oxazolidone derivatives as highly potent N-acylethanolamine acid amidase (NAAA) inhibitors

N-Acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme that catalyzes the hydrolysis of endogenous fatty acid ethanolamides (FAEs), such as N-palmitoylethanolamide (PEA). PEA exhibits anti-inflammatory and analgesic activities by engaging peroxisome proliferator-activated receptor α (PPAR-α). Preventing PEA degradation by inhibition of NAAA has been proposed as a novel strategy for the treatment of inflammation and pain. In the present study, we reported the discovery of the oxazolidone derivative as a novel scaffold for NAAA inhibitors, and studied the structure-activity relationship (SAR) by modification of the side chain and terminal lipophilic substituents. The results showed that the link chain length of C5, straight and saturated linkages were the preferred shape patterns for NAAA inhibition. Several nanomolar NAAA inhibitors were described, including 2f, 3h, 3i and 3j with IC50 values of 270 nM, 150 nM, 100 nM and 190 nM, respectively. Enzymatic degradation studies suggested that 2f inhibited NAAA in a selective, noncompetitive and reversible pattern. Moreover, 2f showed high anti-inflammatory and analgesic activities after systemic and oral administration.

Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products

Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.

Enantioselective Oxidative Aerobic Dealkylation of N-Ethyl Benzylisoquinolines by Employing the Berberine Bridge Enzyme

N-Dealkylation methods are well described for organic chemistry and the reaction is known in nature and drug metabolism; however, to our knowledge, enantioselective N-dealkylation has not been yet reported. In this study, exclusively the (S)-enantiomers o

1,2,3-Triazole-containing uracil derivatives with excellent pharmacokinetics as a novel class of potent human deoxyuridine triphosphatase inhibitors

Deoxyuridine triphosphatase (dUTPase) has emerged as a potential target for drug development as a 5-fluorouracil-based combination chemotherapy. We describe the design and synthesis of a novel class of human dUTPase inhibitors, 1,2,3-triazole-containing u

Biocatalytic enantioselective oxidative C-C coupling by aerobic C-H activation

Bridging the gap: The berberine bridge enzyme (BBE) was employed for the first preparative oxidative biocatalytic C-C coupling that leads to a new intramolecular bond. This unique transformation requires O2 as sole stoichiometric oxidant and gives access to novel optically pure (S)-berbine 2 and (R)-1-benzyl-1,2,3,4-tetrahydroisoquinoline 1 alkaloid derivatives by kinetic resolution.

Biocatalytic organic synthesis of optically pure (S)-scoulerine and berbine and benzylisoquinoline alkaloids

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4-8 linear steps using either a Bischler-Napieralski cyclization or a C1-Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5-9 linear steps.

Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents

The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the β-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46 and 47 displayed the most potent antiproliferative activity of the series. β-Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells (IC50 = 0.8 nM) together with significant in vitro inhibition of tubulin polymerization and has been selected for further biochemical assessment. These novel β-lactam compounds are identified as potentially useful scaffolds for the further development of antitumor agents that target tubulin.

BETA-LACTAMASE INHIBITORS

Disclosed herein are alpha-aminoboronic acids and their derivatives which act as inhibitors of beta-lactamases. Also disclosed herein are pharmaceutical compositions comprising alpha-aminoboronic acids and methods of use thereof.

Selective estrogen receptor modulators with conformationally restricted side chains. Synthesis and structure-activity relationship of ERα-selective tetrahydroisoquinoline ligands

We disclose herein the discovery of estrogen receptor α (ERα) selective estrogen receptor modulators (SERMs) of the tetrahydroisoquinoline series that incorporate novel conformationally restricted side chains as replacement of the aminoethoxy residue typical of SERMs. Molecular modeling studies used in conjunction with the X-ray crystal structure of the ERα ligand binding domain (LBD) with raloxifene (7) suggested a diazadecaline moiety as a viable mimic of the SERM side chain. On the basis of this knowledge, the piperidinylethoxy moiety of our lead compound 60 was replaced by a diazadecaline subunit, providing the novel tetrahydroisoquinoline 29. In addition to exhibiting a binding affinity to ERα and antagonistic properties in the estrogen response element and MCF-7 assays similar to those of the parent compound 60, ligand 29 showed a reduced agonist behavior in the MCF-7 assay in the absence of 17β-estradiol. These data point toward the fact that 29 may have a potential for breast cancer prevention/treatment in vivo, a feature which is particularly attractive in the quest for safe alternatives to hormone replacement therapy. In a pharmacokinetic experiment carried out in rats, 29 displayed an interesting profile, with a bioavailability of 49%. We also disclose the X-ray crystal structure of 29 in complex with ERα-LBD, which reveals the preferred configurations of 29 at the two chiral centers and the details of its interactions with the receptor. Finally, our structure-activity relationship studies show that other analogues bearing constrained side chains retain potency and antagonist activity and that a 3-OH substituted phenyl D-ring increases the selectivity of a set of piperazinyl-containing ligands in favor of ERα over ERβ.

Compounds and methods for modulation of estrogen receptors

Compounds that modulate the estrogen receptor (ER) are disclosed, as well as pharmaceutical compositions containing the same. In a specific embodiment, the compounds are selective for ER-β over ER-α. Methods are disclosed for modulating ER-β in cell and/o