JDTic

JDTic
IUPAC ime
	(3R)-7-hydroxy- N-((1S)-1[(3R,4R)-4- (3-hydroxyphenyl)- 3,4-dimethylpiperidin- 1-yl]methyl 2-methylpropyl)- 1,2,3,4-tetrahydroisoquinoline- 3-carboxamide
Identifikatori
CAS broj	361444-66-8 ; 785835-79-2 (hidrohlorid)
PubChem	CID 9956146
Sinonimi	JDTic
Hemijski podaci
Formula	C28H39N3O3
Molarna masa	465.626 g/mol
	SMILES C[C@H]1CN(CC[C@@]1(C)C2=CC(=CC=C2)O)C[C@H](C(C)C)NC(=O)[C@H]3CC4=C(CN3)C=C(C=C4)O; ;

JDTic je lek, koji je visoko selektivni κ-opioidni antagonist. On blokira taj receptor bez vršenja uticaja na μ- ili δ- opioidne receptore.^[1] On je derivat 4-fenilpiperidina, koji je u nekoj meri strukturno srodan sa analgeticima kao što su meperidin i ketobemidon, i bliže sa mi opioidnim antagonistom alvimopanom. On se strukturno razlikuje od drugih kapa antagonist,a kao što je norbinaltorfimin.^[2]^[3]

On ima veoma dugo vreme dejstva, sa efektima na životinjama primetnim do nekoliko nedelja nakon administracije jedne doze,^[4] mada njegovo vezivanje za kapa opioidni receptor nije nepovratno i njegovi dugotrajno dejstvo je umesto toga uzrokovano promenama aktivnosti c-Jun N-terminalne kinaze.^[5] Iz životinjska ispitivanja proizilazi da on može da proizvede antidepresantske i anksioloitičke efekte,^[6] kao i da može da ima primenu u lečenju adikcije na kokain i morfin.^[7]^[8]

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Norbinaltorfimin

Reference

^ Thomas, J. B.; Atkinson, R. N.; Rothman, R. B.; Fix, S. E.; Mascarella, S. W.; Vinson, N. A.; Xu, H.; Dersch, C. M.; Lu, Y.; Cantrell, B. E.; Zimmerman, D. M.; Carroll, F. I. (2001). „Identification of the first trans-(3R,4R)- dimethyl-4-(3-hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity”. Journal of Medicinal Chemistry. 44 (17): 2687—90. PMID 11495579. doi:10.1021/jm015521r.
^ Thomas, J. B.; Atkinson, R. N.; Vinson, N. A.; Catanzaro, J. L.; Perretta, C. L.; Fix, S. E.; Mascarella, S. W.; Rothman, R. B.; Xu, H.; Dersch, C. M.; Cantrell, B. E.; Zimmerman, D. M.; Carroll, F. I. (2003). „Identification of (3R)-7-hydroxy-N-((1S)-1-(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl-1-piperidinylmethyl-2-methylpropyl)-1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide as a novel potent and selective opioid kappa receptor antagonist”. Journal of Medicinal Chemistry. 46 (14): 3127—37. PMID 12825951. doi:10.1021/jm030094y.
^ Cai, T. B.; Zou, Z.; Thomas, J. B.; Brieaddy, L.; Navarro, H. A.; Carroll, F. I. (2008). „Synthesis and in vitro opioid receptor functional antagonism of analogues of the selective kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinylmethyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic)”. Journal of Medicinal Chemistry. 51 (6): 1849—60. PMID 18307295. doi:10.1021/jm701344b.
^ Carroll, I.; Thomas, J. B.; Dykstra, L. A.; Granger, A. L.; Allen, R. M.; Howard, J. L.; Pollard, G. T.; Aceto, M. D.; Harris, L. S. (2004). „Pharmacological properties of JDTic: A novel kappa-opioid receptor antagonist”. European Journal of Pharmacology. 501 (1–3): 111—119. PMID 15464069. doi:10.1016/j.ejphar.2004.08.028.
^ Bruchas, M. R.; Yang, T.; Schreiber, S.; Defino, M.; Kwan, S. C.; Li, S.; Chavkin, C. (2007). „Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase”. The Journal of Biological Chemistry. 282 (41): 29803—11. PMC 2096775 . PMID 17702750. doi:10.1074/jbc.M705540200 .
^ Knoll, A. T.; Meloni, E. G.; Thomas, J. B.; Carroll, F. I.; Carlezon Jr, W. A. (2007). „Anxiolytic-like effects of kappa-opioid receptor antagonists in models of unlearned and learned fear in rats”. The Journal of Pharmacology and Experimental Therapeutics. 323 (3): 838—45. PMID 17823306. S2CID 28128824. doi:10.1124/jpet.107.127415.
^ Beardsley, P. M.; Howard, J. L.; Shelton, K. L.; Carroll, F. I. (2005). „Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats”. Psychopharmacology. 183 (1): 118—26. PMID 16184376. S2CID 31140425. doi:10.1007/s00213-005-0167-4.
^ Carroll, F. I.; Harris, L. S.; Aceto, M. D. (2005). „Effects of JDTic, a selective kappa-opioid receptor antagonist, on the development and expression of physical dependence on morphine using a rat continuous-infusion model”. European Journal of Pharmacology. 524 (1–3): 89—94. PMID 16236279. doi:10.1016/j.ejphar.2005.09.013.

Spoljašnje veze

Molimo Vas, obratite pažnju na važno upozorenje
u vezi sa temama iz oblasti medicine (zdravlja).

[1] Thomas, J. B.; Atkinson, R. N.; Rothman, R. B.; Fix, S. E.; Mascarella, S. W.; Vinson, N. A.; Xu, H.; Dersch, C. M.; Lu, Y.; Cantrell, B. E.; Zimmerman, D. M.; Carroll, F. I. (2001). „Identification of the first trans-(3R,4R)- dimethyl-4-(3-hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity”. Journal of Medicinal Chemistry. 44 (17): 2687—90. PMID 11495579. doi:10.1021/jm015521r.

[2] Thomas, J. B.; Atkinson, R. N.; Vinson, N. A.; Catanzaro, J. L.; Perretta, C. L.; Fix, S. E.; Mascarella, S. W.; Rothman, R. B.; Xu, H.; Dersch, C. M.; Cantrell, B. E.; Zimmerman, D. M.; Carroll, F. I. (2003). „Identification of (3R)-7-hydroxy-N-((1S)-1-(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl-1-piperidinylmethyl-2-methylpropyl)-1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide as a novel potent and selective opioid kappa receptor antagonist”. Journal of Medicinal Chemistry. 46 (14): 3127—37. PMID 12825951. doi:10.1021/jm030094y.

[3] Cai, T. B.; Zou, Z.; Thomas, J. B.; Brieaddy, L.; Navarro, H. A.; Carroll, F. I. (2008). „Synthesis and in vitro opioid receptor functional antagonism of analogues of the selective kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinylmethyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic)”. Journal of Medicinal Chemistry. 51 (6): 1849—60. PMID 18307295. doi:10.1021/jm701344b.

[4] Carroll, I.; Thomas, J. B.; Dykstra, L. A.; Granger, A. L.; Allen, R. M.; Howard, J. L.; Pollard, G. T.; Aceto, M. D.; Harris, L. S. (2004). „Pharmacological properties of JDTic: A novel kappa-opioid receptor antagonist”. European Journal of Pharmacology. 501 (1–3): 111—119. PMID 15464069. doi:10.1016/j.ejphar.2004.08.028.

[5] Bruchas, M. R.; Yang, T.; Schreiber, S.; Defino, M.; Kwan, S. C.; Li, S.; Chavkin, C. (2007). „Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase”. The Journal of Biological Chemistry. 282 (41): 29803—11. PMC 2096775 . PMID 17702750. doi:10.1074/jbc.M705540200 .

[6] Knoll, A. T.; Meloni, E. G.; Thomas, J. B.; Carroll, F. I.; Carlezon Jr, W. A. (2007). „Anxiolytic-like effects of kappa-opioid receptor antagonists in models of unlearned and learned fear in rats”. The Journal of Pharmacology and Experimental Therapeutics. 323 (3): 838—45. PMID 17823306. S2CID 28128824. doi:10.1124/jpet.107.127415.

[7] Beardsley, P. M.; Howard, J. L.; Shelton, K. L.; Carroll, F. I. (2005). „Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats”. Psychopharmacology. 183 (1): 118—26. PMID 16184376. S2CID 31140425. doi:10.1007/s00213-005-0167-4.

[8] Carroll, F. I.; Harris, L. S.; Aceto, M. D. (2005). „Effects of JDTic, a selective kappa-opioid receptor antagonist, on the development and expression of physical dependence on morphine using a rat continuous-infusion model”. European Journal of Pharmacology. 524 (1–3): 89—94. PMID 16236279. doi:10.1016/j.ejphar.2005.09.013.

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Reference

Spoljašnje veze

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