Tebaniciclina

Tebaniciclina
Nombre IUPAC
	5-([(2R)-azetidin- 2-il] metoxi)- 2-cloropiridina
General
Fórmula estructural
Fórmula molecular	C9H11N2ClO
Identificadores
Número CAS	198283-73-7
ChEMBL	CHEMBL430497
PubChem	9815575
UNII	9KX8NKV538
	SMILES C1CN[C@H]1COC2=CN=C(C=C2)Cl
	InChI InChI=InChI=1S/C9H11ClN2O/c10-9-2-1-8(5-12-9)13-6-7-3-4-11-7/h1-2,5,7,11H,3-4,6H2/t7-/m1/s1; Key: MKTAGSRKQIGEBH-SSDOTTSWSA-N
Propiedades físicas
Masa molar	198 649 g/mol
Riesgos
Riesgos principales	Perjudicial
	Valores en el SI y en condiciones estándar; (25 ℃ y 1 atm), salvo que se indique lo contrario.
	[editar datos en Wikidata]

La tebaniciclina (de nombre IUPAC 5-([(2R)-azetidin- 2-il] metoxi)- 2-cloropiridina)) es un compuesto heterocíclico que actúa como agonista parcial de los receptores nicotínicos de la acetilcolina y que fue sintetizado por los laboratorios Abbott dentro del contexto de la búsqueda de analgésicos análogos a la epibatidina^[2]^[3]^[4]^[5]^[6]^[7] pero sin el nivel de toxicidad de ésta. En comparación con ella, y pese a que la actividad analgésica es mayor dado que muestra más selectividad en su unión con los receptores neuronales del subtipo α4β2 [1], no superó la Fase II de su desarrollo como producto farmacéutico dado que producía serias complicaciones gastrointestinales.^[8]

En el intento de sintetizar análogos de la tebaniclina más selectivos y que minimicen los efectos secundarios, se ha tratado de aumentar su rigidez sustituyendo el enlace éter por aminas secundarias cíclicas. Dicha ciclación se lleva a cabo por medio de compuestos azoicos ya sea vía formación de puentes, de tiaminas bicíclicas fusionadas o de aminas spirobicíclicas.

Existen diferentes métodos para sintetizar la tebaniciclina, todos ellos publicados en diferentes medios de divulgación científica (Tethraedron,^[9] Med. Chem.,^[10] Drugs Fut,^[11] Abbott lab.^[12]).

Referencias

↑ Número CAS
↑ Donnelly-Roberts, DL; Puttfarcken, PS; Kuntzweiler, TA; Briggs, CA; Anderson, DJ; Campbell, JE; Piattoni-Kaplan, M; Mckenna, DG et al. (1998). "ABT-594 (R)-5-(2-azetidinylmethoxy)-2-chloropyridine: a novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization". The Journal of pharmacology and experimental therapeutics 285 (2): 777–86. PMID 9580626
↑ Bannon, AW; Decker, MW; Curzon, P; Buckley, MJ; Kim, DJ; Radek, RJ; Lynch, JK; Wasicak, JT et al. (1998). "ABT-594 (R)-5-(2-azetidinylmethoxy)-2-chloropyridine: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization". The Journal of pharmacology and experimental therapeutics 285 (2): 787–94. PMID 9580627
↑ Decker, MW; Bannon, AW; Buckley, MJ; Kim, DJ; Holladay, MW; Ryther, KB; Lin, NH; Wasicak, JT et al. (1998). "Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice". European journal of pharmacology 346 (1): 23–33. doi:10.1016/S0014-2999(98)00042-9. PMID 9617748
↑ Kesingland, AC; Gentry, CT; Panesar, MS; Bowes, MA; Vernier, JM; Cube, R; Walker, K; Urban, L (2000). "Analgesic profile of the nicotinic acetylcholine receptor agonists, (+)-epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain". Pain 86 (1-2): 113–8. doi:10.1016/S0304-3959(00)00233-5. PMID 10779668
↑ Sorbera LA, Revel L, Leeson PA, Castaner J. ABT-594. Drugs Future 2001; 26: 927-934.
↑ Lynch Jj, 3.; Wade, C.; Mikusa, J.; Decker, M.; Honore, P. (2005). "ABT-594 (a nicotinic acetylcholine agonist): anti-allodynia in a rat chemotherapy-induced pain model". European journal of pharmacology 509 (1): 43–48. doi:10.1016/j.ejphar.2004.12.034. PMID 15713428
↑ Jain, K. K. Curr. Opin. Inv. Drugs, 2004, 5, 76-81
↑ . Holladay, M.W.; Ryther, K.B.; Hsiao, C.-N.; Morton, H.E.; Lynch, J.K.; King, S.A.; Bai, H.; Dickman, D.A.; Arnold, W.; Efficient asymmetric synthesis of ABT-594; a potent, orally effective analgesic. Tetrahedron Asymmetry 1998, 9, 16, 2791
↑ Lin, N.-H.; Wasicak, J.T.; Holladay, M.W.; et al.; Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic
↑ Nickel, A.; Xiao, Y.; Krow, G.R.; Swan, S.A.; Cannon, K.; An alternative synthesis of 2-chloro-5-hydroxypyridine: A key component of the non-opioid analgesic agent ABT-594. Synth Commun 2000, 30, 22, 4093
↑ Wasicak, J.T.; Ehrlich, P.P.; Sullivan, J.P.; Ryther, K.B.; Or, Y.S.; Lin, N.-H.; Dart, M.J.; Bai, H.; Arneric, S.P.; Holladay, M.W.; Lynch, J.K. (Abbott Laboratories Inc.); 3-Pyridyl enantiomers and their use as analgesics. EP 0950057; JP 2001504857; WO es/10_7

Datos: Q76279183
Multimedia: Tebanicline / Q76279183

[1] Número CAS

[2] Donnelly-Roberts, DL; Puttfarcken, PS; Kuntzweiler, TA; Briggs, CA; Anderson, DJ; Campbell, JE; Piattoni-Kaplan, M; Mckenna, DG et al. (1998). "ABT-594 (R)-5-(2-azetidinylmethoxy)-2-chloropyridine: a novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization". The Journal of pharmacology and experimental therapeutics 285 (2): 777–86. PMID 9580626

[3] Bannon, AW; Decker, MW; Curzon, P; Buckley, MJ; Kim, DJ; Radek, RJ; Lynch, JK; Wasicak, JT et al. (1998). "ABT-594 (R)-5-(2-azetidinylmethoxy)-2-chloropyridine: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization". The Journal of pharmacology and experimental therapeutics 285 (2): 787–94. PMID 9580627

[4] Decker, MW; Bannon, AW; Buckley, MJ; Kim, DJ; Holladay, MW; Ryther, KB; Lin, NH; Wasicak, JT et al. (1998). "Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice". European journal of pharmacology 346 (1): 23–33. doi:10.1016/S0014-2999(98)00042-9. PMID 9617748

[5] Kesingland, AC; Gentry, CT; Panesar, MS; Bowes, MA; Vernier, JM; Cube, R; Walker, K; Urban, L (2000). "Analgesic profile of the nicotinic acetylcholine receptor agonists, (+)-epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain". Pain 86 (1-2): 113–8. doi:10.1016/S0304-3959(00)00233-5. PMID 10779668

[6] Sorbera LA, Revel L, Leeson PA, Castaner J. ABT-594. Drugs Future 2001; 26: 927-934.

[7] Lynch Jj, 3.; Wade, C.; Mikusa, J.; Decker, M.; Honore, P. (2005). "ABT-594 (a nicotinic acetylcholine agonist): anti-allodynia in a rat chemotherapy-induced pain model". European journal of pharmacology 509 (1): 43–48. doi:10.1016/j.ejphar.2004.12.034. PMID 15713428

[8] Jain, K. K. Curr. Opin. Inv. Drugs, 2004, 5, 76-81

[9] . Holladay, M.W.; Ryther, K.B.; Hsiao, C.-N.; Morton, H.E.; Lynch, J.K.; King, S.A.; Bai, H.; Dickman, D.A.; Arnold, W.; Efficient asymmetric synthesis of ABT-594; a potent, orally effective analgesic. Tetrahedron Asymmetry 1998, 9, 16, 2791

[10] Lin, N.-H.; Wasicak, J.T.; Holladay, M.W.; et al.; Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic

[11] Nickel, A.; Xiao, Y.; Krow, G.R.; Swan, S.A.; Cannon, K.; An alternative synthesis of 2-chloro-5-hydroxypyridine: A key component of the non-opioid analgesic agent ABT-594. Synth Commun 2000, 30, 22, 4093

[12] Wasicak, J.T.; Ehrlich, P.P.; Sullivan, J.P.; Ryther, K.B.; Or, Y.S.; Lin, N.-H.; Dart, M.J.; Bai, H.; Arneric, S.P.; Holladay, M.W.; Lynch, J.K. (Abbott Laboratories Inc.); 3-Pyridyl enantiomers and their use as analgesics. EP 0950057; JP 2001504857; WO es/10_7

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