A new route for isoquinolines catalyzed by palladium

Cho, Chan Sik; Patel, Daksha

doi:10.1016/j.molcata.2006.07.011

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…Cyclization of the bromoaldehyde ( 64 ) with 65 affords the isoquinoline ( 66 ), which undergoes PtO 2 -catalyzed hydrogenation to provide 67 (Scheme ). The dicarboxylate ( 67 ) cyclizes with the amine in 62 to form 68 after deprotection of the Boc group. Methylation of the amine in 68 affords the cereblon ligand ( 28 ).…”

Section: Chemistrymentioning

confidence: 99%

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Discovery of ARD-1676 as a Highly Potent and Orally Efficacious AR PROTAC Degrader with a Broad Activity against AR Mutants for the Treatment of AR + Human Prostate Cancer

Xiang,

Zhao,

Han

et al. 2023

J. Med. Chem.

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We report herein the discovery and extensive characterization of ARD-1676, a highly potent and orally efficacious PROTAC degrader of the androgen receptor (AR). ARD-1676 was designed using a new class of AR ligands and a novel cereblon ligand. It has DC50 values of 0.1 and 1.1 nM in AR+ VCaP and LNCaP cell lines, respectively, and IC50 values of 11.5 and 2.8 nM in VCaP and LNCaP cell lines, respectively. ARD-1676 effectively induces degradation of a broad panel of clinically relevant AR mutants. ARD-1676 has an oral bioavailability of 67, 44, 31, and 99% in mice, rats, dogs, and monkeys, respectively. Oral administration of ARD-1676 effectively reduces the level of AR protein in the VCaP tumor tissue in mice and inhibits tumor growth in the VCaP mouse xenograft tumor model without any sign of toxicity. ARD-1676 is a highly promising development candidate for the treatment of AR+ human prostate cancer.

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Section: Chemistrymentioning

confidence: 99%

“…The title compound was synthesized in a 75% yield from the intermediate 2-(tert-butyl)-6,7-dimethyl 3,4dihydroisoquinoline-2,6,7(1H)-tricarboxylate42 following the procedure used for the 5-membered ring tricyclic cereblon ligand. UPLC− MS: 1.0 min, purity > 95%, MS [M + H] + ; found, 314.15, calcd, 314.11.…”

mentioning

confidence: 99%

Discovery of ARD-1676 as a Highly Potent and Orally Efficacious AR PROTAC Degrader with a Broad Activity against AR Mutants for the Treatment of AR + Human Prostate Cancer

Xiang,

Zhao,

Han

et al. 2023

J. Med. Chem.

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show abstract

“…4.1.5. Ethyl 1,3,4,5,6,7,8, 14.29, 22.48, 25.06, 25.20, 26.16, 26.25, 26.78, 64.33, 100.49, 131.34, 158.39, 168.57, 171.94 3,4,5,6,7,8,9,10,11,12,13-dodecahydro-3-oxocyclododeca[c] 13.80, 20.99, 21.79, 22.10, 22.72, 23.99, 24.21, 24.53, 24.59, 24.94, 25.00, 63.93, 99.97, 132.37, 157.27, 168.66, 171.22 3,4,5,6,7-hexahydro-3-oxo-6-phenylisobenzofuran-1-carboxylate (2h) Oil; diastereoisomeric mixture; 1 H NMR (CDCl 3 ) d 1.30 (t, J = 7.0 Hz, 3/2H), 1.31 (t, J = 7.0 Hz, 3/2H), 1.76-1.90 (m, 1H), 2.09-2.13 (m, 1H), 2.30-2.54 (m, 3H), 2.67-2.75 (m, 1H), 2.90-3.00 (m, 1H), 4.28 (q, J = 7.0 Hz, 2H), 5.28-5.30 (m, 1H), 7.20-7.27 (m, 3H), 7.32-7.36 (m, 2H); 13 …”

Section: General Procedures For Palladium-catalyzed Carbonylative Cyclmentioning

confidence: 99%

“…As part of our continuing studies directed towards transition metal-catalyzed cyclization reactions, we recently reported on the synthesis of several cyclic compounds using such a palladium-catalyzed cyclization protocol. Among them, several aldehydes such as b-bromovinyl aldehydes, 2-bromobenzaldehydes and 3-bromopyridine-4-carbaldehydes were found to be coupled and cyclized with suitably functionalized alkenes in the presence of a palladium catalyst to give benzenes, naphthalenes and isoquinolines, respectively, via tandem Heck and aldol reactions [2][3][4]. It is also reported by us that indazoles and pyrazoles can be synthesized by palladium-catalyzed intramolecular carbon-nitrogen bond forming reaction of 2-bromobenzaldehydes and b-bromovinyl aldehydes with arylhydrazines [5,6].…”

Section: Introductionmentioning

confidence: 99%