Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain

Nam, Mina; Kwak, Jinsook; Seo, Seon Hee; Ko, Min Kyung; Lim, Eic Ju; Min, Seungjae; Cho, Yong Seo; Keum, Gyochang; Baek, Du-Jong; Lee, Jiyoun; Pae, Ae Nim

doi:10.1016/j.ejmech.2015.04.060

Cited by 14 publications

(5 citation statements)

References 38 publications

(21 reference statements)

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“…After installation of a Boc group to 10f , the intermediate 12 was hydrolyzed into the corresponding acid and then reacted with methyl( S )-4-(1-aminoethyl)benzoate to furnish the intermediate 13 . After removal of the Boc group, compound 13 was reacted with 4-fluorobenzoyl chloride, m -trifluoromethylbenzaldehyde, or p -trifluoromethylbenzyl bromide followed by ester hydrolysis to afford the desired products 26 , 27 , and 28 , respectively. , At the same time, 10f was subjected to a Sandmeyer iodination reaction and then underwent a Sonogashira cross-coupling reaction with different alkynes to furnish the intermediates 14a–d . The desired compounds 29–32 were prepared from 14a–d by successive ester hydrolysis, HATU coupling reaction, and ester hydrolysis.…”

Section: Results and Discussionmentioning

confidence: 99%

“…After removal of the Boc group, compound 13 was reacted with 4fluorobenzoyl chloride, m-trifluoromethylbenzaldehyde, or ptrifluoromethylbenzyl bromide followed by ester hydrolysis to afford the desired products 26, 27, and 28, respectively. 33,34 At the same time, 10f was subjected to a Sandmeyer iodination In Vitro Functional Studies. The calcium flux assay is a universal functional assay for rapidly screening GPCR ligands.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Scaffold Hopping Strategy to Identify Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy

Wang

Yang

et al. 2022

J. Med. Chem.

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Cancer cells can effectively suppress the natural immune response in humans, and prostaglandin E2 (PGE2) is a key mediator in the development of tumor cell resistance to immunotherapy. As a major contributor to PGE2-elicited immunosuppressive activity, the EP4 receptor promotes tumor development and progression in the tumor microenvironment, and the development of selective and potent EP4 receptor antagonists should have promising potential for tumor immunotherapy. Aiming at improving the drug-like properties, a series of 4,7-dihydro-5H-thieno[2,3-c]pyran derivatives were designed and synthesized through a scaffold hopping strategy. The most promising compound 47 exhibited good EP4 antagonistic activity and excellent subtype selectivity, as well as favorable drug-like properties. It effectively suppressed the expression of multiple immunosuppression-related genes in macrophages. Meanwhile, oral administration of compound 47, alone or in combination with anti-PD-1 antibody, significantly enhanced the antitumor immune response and inhibited tumor growth in the mouse CT26 colon carcinoma model.

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Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Scaffold Hopping Strategy to Identify Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy

Wang

Yang

et al. 2022

J. Med. Chem.

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“…Truini et al [80] propose testing and ultimately using NAC for the treatment of pain. Similarly, Nam et al [81] found specific antagonists of metabotropic glutamate receptors to mediate analgesia in rodent test subjects.…”

Section: How Do Pharmacological Interventions Take Advantage Of Pamentioning

confidence: 98%

Transmission pathways and mediators as the basis for clinical pharmacology of pain

Kirkpatrick

McEntire

Smith

et al. 2016

Expert Review of Clinical Pharmacology

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Introduction Mediators in pain transmission are the targets of a multitude of different analgesic pharmaceuticals. This review explores the most significant mediators of pain transmission as well as the pharmaceuticals that act on them. Areas Covered The review explores many of the key mediators of pain transmission. In doing so, this review uncovers important areas for further research. It also highlights agents with potential for producing novel analgesics, probes important interactions between pain transmission pathways that could contribute to synergistic analgesia, and emphasizes transmission factors that participate in transforming acute injury into chronic pain. Expert Commentary This review examines current pain research, particularly in the context of identifying novel analgesics, highlighting interactions between analgesic transmission pathways, and discussing factors that may contribute to the development of chronic pain after an acute injury.

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“…Neuropathic pain can be brought on by a variety of stimulation that damage the nerves in the peripheral and central nervous system, but the clinical symptoms of the pain are consistent throughout the several neuropathic syndromes and reasons (Baron, 2006;Kim et al, 2016). Recent studies on the causes of neuropathic pain have revealed that a nerve injury causes significant modifications in the neurological system, setting it apart from other kinds of chronic pain that are characterized by an unbroken nociceptive system (nociceptive pain) (Nam et al, 2015). Furthermore, whereas nociceptive pain can be effectively treated with nociceptive medicines, neuropathic pain requires other therapy.…”

Section: Neuropathic Painmentioning

confidence: 99%

Neuropathy; its profile and experimental nerve injury neuropathic pain models: A Review

Kumar

2023

Preprint

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Neuropathy is a terrible disorder that has a wide range of aetiologies. Drug-Induced Neuropathy, which happens whenever a chemical agent damages the peripheral nerve system, has been linked here to iatrogenic creation of some drugs. It is potentially permanent and causes sensory impairments and paresthesia that typically affects the hands, feet, and stockings; motor participation is uncommon. It might appear suddenly or over time, and the long-term outlook varies. The wide range of chronic pain conditions experienced by people has been some of the main obstacles to developing new, more effective medications for the treatment of neuropathic pain. Animal models can be used to examine various neuropathic pain aetiologies and symptoms. Several models investigate the peripheral processes of neuropathic pain, whereas some even investigate the central mechanisms. such as drug induce models like vincristine, cisplatin, bortezomib, or thalidomide, etc., and surgical models like sciatic nerve chronic constriction injury (CCI), sciatic nerve ligation through spinal nerve ligation (SNL), sciatic nerve damage caused by a laser, SNI (spared nerve injury), etc. The more popular animal models relying on peripheral nerve ligatures are explained. In contrast to chronic sciatic nerve contraction, which results in behavioral symptoms of less reliable stressful neuropathies, (SNI) spared nerve injury generates behavioral irregularities which are more feasible over a longer period. This review summarizes the latest methods models as well as clinical ideas concerning this mechanism. Every strongest current information on neuropathy is discussed, along with several popular laboratory models for causing neuropathy.

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Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain

Cited by 14 publications

References 38 publications

Scaffold Hopping Strategy to Identify Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy

Scaffold Hopping Strategy to Identify Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy

Transmission pathways and mediators as the basis for clinical pharmacology of pain

Neuropathy; its profile and experimental nerve injury neuropathic pain models: A Review

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