Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: Synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet)

Wada, Naohisa; Fujii, H.; Koyano, Koji; Hirayama, Shigeto; Iwai, Takashi; Nemoto, Toru; Nagase, Hiroshi

doi:10.1016/j.bmcl.2012.10.023

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…SYK‐385 also showed the highest selectivity for the MOR over the KOR among all the reported MOR‐selective nonpeptide ligands. In contrast, compounds with a bulky substituent ( i ‐butyl or benzyl group) on the 17‐nitrogen had very low affinities for the opioid receptors .…”

Section: Synthesis Of Double‐capped Triplet Drugs With Morphinan Skelmentioning

confidence: 94%

Synthesis of Novel Triplets with a 1,3,5‐Trioxazatriquinane Skeleton and Their Pharmacologies for Opioid Receptors

Nagase

Kutsumura

2015

Archiv der Pharmazie

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We designed and synthesized novel triplet molecules with 1,3,5-trioxazatriquinane skeletons. One class comprises double-capped triplets with a morphinan skeleton; the other class comprises simple phenol derivatives with phenethylamine moieties. One compound with m-phenolic hydroxyl group, called SYK-146, is a highly selective, potent agonist for the κ receptor, with activity nearly equivalent to that of U-50488H. The o-phenolic isomer of SYK-146, called SYK-524, showed potent but non-selective agonistic activity for the opioid receptors. We also added several simple phenol derivatives to a library of compounds that target opioid receptors, and they showed high hit rates for the receptor. This library might also be expected to show high hit rates for other receptors.

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Section: Synthesis Of Double‐capped Triplet Drugs With Morphinan Skelmentioning

confidence: 94%

Synthesis of Novel Triplets with a 1,3,5‐Trioxazatriquinane Skeleton and Their Pharmacologies for Opioid Receptors

Nagase

Kutsumura

2015

Archiv der Pharmazie

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“…12 It is interesting that SYK-385 exhibited the highest selectivity for the MOR over the KOR among the reported MOR selective nonpeptide ligands. 12 Although these results predicted that the 1,3,5-trioxazatriquinane derivatives would exert novel pharmacological profiles, all the above-mentioned derivatives contained large morphinan units.…”

mentioning

confidence: 99%

“…The antinociception induced by KNT-93 and KNT-123 was 54- and 5-fold more potent, respectively, than that of morphine. , 4,5-Epoxymorphinan derivative SYK-134 (Figure ) with the 1,3,5-trioxazatriquinane moiety, which was synthesized as an analog of KNT-93 and -123, showed agonistic activity selective to the KOR, while another derivative SYK-385 (Figure ) was a selective MOR agonist . It is interesting that SYK-385 exhibited the highest selectivity for the MOR over the KOR among the reported MOR selective nonpeptide ligands .…”

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confidence: 99%

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confidence: 99%

“…According to the previously reported method, , we prepared compounds 1a – c (R = m -OH), 8a – d , and 11a , b . The synthesis of compounds 1a – c (R = m -OH) commenced with m -methoxyacetophenone ( 2 ).…”

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confidence: 99%

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Synthesis and Pharmacology of a Novel κ Opioid Receptor (KOR) Agonist with a 1,3,5-Trioxazatriquinane Skeleton

Hirayama

Wada

Nemoto

et al. 2014

ACS Med. Chem. Lett.

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We designed and synthesized the 1,3,5-trioxazatriquinane derivatives with m-hydroxyphenyl groups. These compounds include the phenethylamine structure within them, which is a common structure observed in morphinan derivatives like morphine. Among the synthesized compounds, (−)-8c with two m-hydroxyphenyl groups selectively bound and exerted full agonist activity toward the κ opioid receptor (KOR). Subcutaneously administered (−)-8c exhibited significant antinociceptive effects via the KOR in a dose-dependent manner. These results suggest the emergence of a novel class of KOR agonist.

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Asymmetric Synthesis of N‐Fused 1,3‐Oxazolidines via Pd‐Catalyzed Decarboxylative (3+2) Cycloaddition

et al. 2020

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Efficient synthesis of optically active Nfused 1,3-oxazolidines containing quaternary and tertiary stereocenters was achieved via Pd-catalyzed asymmetric (3 + 2) cycloadditions of sulfamatederived cyclic imines and vinylethylene carbonates. Using a chiral phosphoramidite ligand, the cycloadditions proceeded effectively providing sulfamidate-fused 1,3-oxazolidines in high yields (up to 96%) with stereoselectivities (up to 25:1 dr; > 99% ee). Additionally, the scale-up reaction and further transformations of the product were also achieved demonstrating the synthetic utility toward the construction of useful heterocycles such as chiral oxazoline bearing a quaternary stereocenter.Scheme 2. Gram-scale synthesis of sulfamidate-fused 1,3-oxazolidine 3 a and its further applications.

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Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: Synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet)

Cited by 7 publications

References 18 publications

Synthesis of Novel Triplets with a 1,3,5‐Trioxazatriquinane Skeleton and Their Pharmacologies for Opioid Receptors

Synthesis of Novel Triplets with a 1,3,5‐Trioxazatriquinane Skeleton and Their Pharmacologies for Opioid Receptors

Synthesis and Pharmacology of a Novel κ Opioid Receptor (KOR) Agonist with a 1,3,5-Trioxazatriquinane Skeleton

Asymmetric Synthesis of N‐Fused 1,3‐Oxazolidines via Pd‐Catalyzed Decarboxylative (3+2) Cycloaddition

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