Your browser doesn't support javascript.
loading
Synthesis and Assessment of Fused ß-Carboline Derivatives as Kappa Opioid Receptor Agonists.
Yadav, Veena D; Kumar, Lalan; Kumari, Poonam; Kumar, Sakesh; Singh, Maninder; Siddiqi, Mohammad I; Yadav, Prem N; Batra, Sanjay.
Afiliación
  • Yadav VD; Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • Kumar L; Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • Kumari P; Neuroscience and Ageing Biology Division, CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • Kumar S; Neuroscience and Ageing Biology Division, CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • Singh M; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, CSIR-HRDC) Campus Sector 19, Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India.
  • Siddiqi MI; Molecular and Structural Biology Division, CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • Yadav PN; Molecular and Structural Biology Division, CSIR-Central Drug Research Institute Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • Batra S; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, CSIR-HRDC) Campus Sector 19, Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India.
ChemMedChem ; 16(12): 1917-1926, 2021 06 17.
Article en En | MEDLINE | ID: mdl-33599108
The synthesis of 5-formyl-6-aryl-6H-indolo[3,2,1-de][1,5] naphthyridine-2-carboxylates by reaction between 1-formyl-9H-ß-carbolines and cinnamaldehydes in the presence of pyrrolidine in water with microwave irradiation is described. Pharmacophoric modification of the formyl group offered several new fused ß-carboline derivatives, which were investigated for their κ-opioid receptor (KOR) agonistic activity. Two compounds 4 a and 4 c produced appreciable agonist activity on KOR with EC50 values of 46±19 and 134±9 nM, respectively. Moreover, compound-induced KOR signaling studies suggested both compounds to be extremely G-protein-biased agonists. The analgesic effect of 4 a was validated by the increase in tail flick latency in mice in a time-dependent manner, which was completely blocked by the KOR-selective antagonist norBNI. Moreover, unlike U50488, an unbiased full KOR agonist, 4 a did not induce sedation. The docking of 4 a with the human KOR was studied to rationalize the result.
Asunto(s)
Palabras clave

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Dolor / Carbolinas / Receptores Opioides kappa / Analgésicos / Antagonistas de Narcóticos Límite: Animals / Humans / Male Idioma: En Revista: ChemMedChem Asunto de la revista: FARMACOLOGIA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: India

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Dolor / Carbolinas / Receptores Opioides kappa / Analgésicos / Antagonistas de Narcóticos Límite: Animals / Humans / Male Idioma: En Revista: ChemMedChem Asunto de la revista: FARMACOLOGIA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: India