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Chemical compound
AM-251
1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N -(1-piperidyl)pyrazole-3-carboxamide
CAS Number PubChem CID ECHA InfoCard 100.162.062 Formula C 22 H 21 Cl 2 I N 4 O Molar mass 555.24 g·mol−1 3D model (JSmol )
O=C(NN1CCCCC1)c4nn(c2ccc(Cl)cc2Cl)c(c3ccc(I)cc3)c4C
InChI=1S/C22H21Cl2IN4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-7-16(23)13-18(19)24)21(14)15-5-8-17(25)9-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)
Y Key:BUZAJRPLUGXRAB-UHFFFAOYSA-N
Y
(verify)
AM-251 is an inverse agonist at the CB1 cannabinoid receptor. AM-251 is structurally very close to rimonabant ; both are biarylpyrazole cannabinoid receptor antagonists . In AM-251, the p -chloro group attached to the phenyl substituent at C-5 of the pyrazole ring is replaced with a p -iodo group. The resulting compound exhibits slightly better binding affinity for the CB1 receptor (with a Ki value of 7.5 nM) than rimonabant, which has a Ki value of 11.5 nM, AM-251 is, however, about two-fold more selective for the CB1 receptor when compared to rimonabant.[ 1] Like rimonabant, it is additionally a μ-opioid receptor antagonist[ 2] that attenuates analgesic effects.[ 3]
AM251 has shown an in vitro antimelanoma activity against pancreatic and colon cancer cells.[ 4]
^ Lan R, Liu Q, Fan P, Lin S, Fernando SR, McCallion D, et al. (February 1999). "Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists". Journal of Medicinal Chemistry . 42 (4): 769–776. doi :10.1021/jm980363y . PMID 10052983 .
^ Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL (October 2012). "AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid/cannabinoid interaction studies" . Neuropharmacology . 63 (5): 905–915. doi :10.1016/j.neuropharm.2012.06.046 . PMC 3408547 . PMID 22771770 .
^ Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL (October 2012). "AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid/cannabinoid interaction studies" . Neuropharmacology . 63 (5): 905–915. doi :10.1016/j.neuropharm.2012.06.046 . PMC 3408547 . PMID 22771770 .
^ Carpi S, Fogli S, Romanini A, Pellegrino M, Adinolfi B, Podestà A, et al. (August 2015). "AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells" (PDF) . Anti-Cancer Drugs . 26 (7): 754–762. doi :10.1097/CAD.0000000000000246 . hdl :11568/750318 . PMID 25974027 . S2CID 205526223 . Archived (PDF) from the original on July 2, 2021.
Phytocannabinoids (comparison )
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Classical cannabinoids (dibenzopyrans) Non-classical cannabinoids Adamantoylindoles Benzimidazoles Benzoylindoles Cyclohexylphenols Eicosanoids Indazole-3- carboxamides Indole-3-carboxamides Indole-3-carboxylates Naphthoylindazoles Naphthoylindoles Naphthoylpyrroles Naphthylmethylindenes Naphthylmethylindoles Phenylacetylindoles Pyrazolecarboxamides Tetramethylcyclo- propanoylindazoles Tetramethylcyclo- propanoylindoles Others
Allosteric CBR Tooltip Cannabinoid receptor ligands Endocannabinoid enhancers (inactivation inhibitors) Anticannabinoids (antagonists/inverse agonists/antibodies)
Receptor (ligands )
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Agonists
2-AG
2-AGE (noladin ether)
3,3'-Diindolylmethane
4-O-Methylhonokiol
α-Amyrin · β-Amyrin
A-796,260
A-834,735
A-836,339
AM-1172
AM-1221
AM-1235
AM-1241
AM-2232
Anandamide
AZ-11713908
Cannabinol
Caryophyllene
CB-13
CBS-0550
CP 55,940
GW-405,833 (L-768,242)
GW-842,166X
HU-308
JTE 7-31
JWH-007
JWH-015
JWH-018
JWH-73
JWH-133
L-759,633
L-759,656
Lenabasum (anabasum)
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MDA-19
Nabitan
NADA
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PF-03550096
S-444,823
SER-601
Serinolamide A
UR-144
Tedalinab
THC (dronabinol)
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NAGly (GPR18 )
GPR55
GPR119
Transporter (modulators )
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Enzyme (modulators )
Others
Others: 2-PG (directly potentiates activity of 2-AG at CB1 receptor)
ARN-272 (FAAH-like anandamide transporter inhibitor)