a-methylated derivatives of 2-arachidonyl glycerol: Synthesis, CB1 receptor activity and enzymatic stability

Teija Parkkari; Ari M.P. Koskinen; Mikko Myllymäki; Juha R. Savinainen; Susanna M. Saario; Joel A. Castillo-Melendez; Jarmo T. Laitinen; Tapio Nevalainen; Tomi Järvinen

doi:10.1016/j.bmcl.2006.01.101

a-methylated derivatives of 2-arachidonyl glycerol: Synthesis, CB1 receptor activity and enzymatic stability

Teija Parkkari, Ari M.P. Koskinen, Mikko Myllymäki, Juha R. Savinainen, Susanna M. Saario, Joel A. Castillo-Melendez, Jarmo T. Laitinen, Tapio Nevalainen, Tomi Järvinen

Tutkimustuotos: Lehtiartikkeli › Article › Scientific › vertaisarvioitu

5 Sitaatiot (Scopus)

186 Lataukset (Pure)

Abstrakti

a-Methylated analogues of the endogenous cannabinoid, 2-arachidonoyl glycerol (2-AG), were synthesized aiming to the improved enzymatic stability of 2-AG. In addition, the CB1 activity properties of fluoro derivatives of 2-AG were studied. The CB1 receptor activity was determined by the [35S]GTPcS binding assay, and the enzymatic stability of a-methylated analogues was determined in rat cerebellar membranes. The results indicate that even if the a-methylated 2-AG derivatives are slightly weaker CB1 receptor agonists than 2-AG, they are clearly more stable than 2-AG. In addition, the results showed that the replacement of the hydroxyl group(s) of 2-AG by fluorine does not improve the CB1 activity of 2-AG.

Alkuperäiskieli	Englanti
Sivut	2437-2440
Julkaisu	Bioorganic and Medicinal Chemistry Letters
Numero	16
DOI - pysyväislinkit	https://doi.org/10.1016/j.bmcl.2006.01.101
Tila	Julkaistu - 2006
OKM-julkaisutyyppi	A1 Julkaistu artikkeli, soviteltu

Tutkimusalat

2 AG
cannabinoidi
CB1 reseptor
enzymatic stability
stereoselective synthesis

Pääsy asiakirjaan

10.1016/j.bmcl.2006.01.101

ms126Accepted author manuscript, 148 KB

SFX-saatavuus

Koko teksti

Siteeraa tätä

Parkkari, T., Koskinen, A. M. P., Myllymäki, M., Savinainen, J. R., Saario, S. M., Castillo-Melendez, J. A., Laitinen, J. T., Nevalainen, T., & Järvinen, T. (2006). a-methylated derivatives of 2-arachidonyl glycerol: Synthesis, CB1 receptor activity and enzymatic stability. Bioorganic and Medicinal Chemistry Letters, (16), 2437-2440. https://doi.org/10.1016/j.bmcl.2006.01.101

@article{92dff427c6d848788a7d0d24148a64d4,

title = "a-methylated derivatives of 2-arachidonyl glycerol: Synthesis, CB1 receptor activity and enzymatic stability",

abstract = "a-Methylated analogues of the endogenous cannabinoid, 2-arachidonoyl glycerol (2-AG), were synthesized aiming to the improved enzymatic stability of 2-AG. In addition, the CB1 activity properties of fluoro derivatives of 2-AG were studied. The CB1 receptor activity was determined by the [35S]GTPcS binding assay, and the enzymatic stability of a-methylated analogues was determined in rat cerebellar membranes. The results indicate that even if the a-methylated 2-AG derivatives are slightly weaker CB1 receptor agonists than 2-AG, they are clearly more stable than 2-AG. In addition, the results showed that the replacement of the hydroxyl group(s) of 2-AG by fluorine does not improve the CB1 activity of 2-AG.",

keywords = "2 AG, cannabinoidi, CB1 reseptor, enzymatic stability, stereoselective synthesis, 2 AG, cannabinoidi, CB1 reseptor, enzymatic stability, stereoselective synthesis, 2 AG, cannabinoidi, CB1 reseptor, enzymatic stability, stereoselective synthesis",

author = "Teija Parkkari and Koskinen, {Ari M.P.} and Mikko Myllym{\"a}ki and Savinainen, {Juha R.} and Saario, {Susanna M.} and Castillo-Melendez, {Joel A.} and Laitinen, {Jarmo T.} and Tapio Nevalainen and Tomi J{\"a}rvinen",

year = "2006",

doi = "10.1016/j.bmcl.2006.01.101",

language = "English",

pages = "2437--2440",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "16",

}

TY - JOUR

T1 - a-methylated derivatives of 2-arachidonyl glycerol: Synthesis, CB1 receptor activity and enzymatic stability

AU - Parkkari, Teija

AU - Koskinen, Ari M.P.

AU - Myllymäki, Mikko

AU - Savinainen, Juha R.

AU - Saario, Susanna M.

AU - Castillo-Melendez, Joel A.

AU - Laitinen, Jarmo T.

AU - Nevalainen, Tapio

AU - Järvinen, Tomi

PY - 2006

Y1 - 2006

N2 - a-Methylated analogues of the endogenous cannabinoid, 2-arachidonoyl glycerol (2-AG), were synthesized aiming to the improved enzymatic stability of 2-AG. In addition, the CB1 activity properties of fluoro derivatives of 2-AG were studied. The CB1 receptor activity was determined by the [35S]GTPcS binding assay, and the enzymatic stability of a-methylated analogues was determined in rat cerebellar membranes. The results indicate that even if the a-methylated 2-AG derivatives are slightly weaker CB1 receptor agonists than 2-AG, they are clearly more stable than 2-AG. In addition, the results showed that the replacement of the hydroxyl group(s) of 2-AG by fluorine does not improve the CB1 activity of 2-AG.

AB - a-Methylated analogues of the endogenous cannabinoid, 2-arachidonoyl glycerol (2-AG), were synthesized aiming to the improved enzymatic stability of 2-AG. In addition, the CB1 activity properties of fluoro derivatives of 2-AG were studied. The CB1 receptor activity was determined by the [35S]GTPcS binding assay, and the enzymatic stability of a-methylated analogues was determined in rat cerebellar membranes. The results indicate that even if the a-methylated 2-AG derivatives are slightly weaker CB1 receptor agonists than 2-AG, they are clearly more stable than 2-AG. In addition, the results showed that the replacement of the hydroxyl group(s) of 2-AG by fluorine does not improve the CB1 activity of 2-AG.

KW - 2 AG

KW - cannabinoidi

KW - CB1 reseptor

KW - enzymatic stability

KW - stereoselective synthesis

KW - 2 AG

KW - cannabinoidi

KW - CB1 reseptor

KW - enzymatic stability

KW - stereoselective synthesis

KW - 2 AG

KW - cannabinoidi

KW - CB1 reseptor

KW - enzymatic stability

KW - stereoselective synthesis

U2 - 10.1016/j.bmcl.2006.01.101

DO - 10.1016/j.bmcl.2006.01.101

M3 - Article

SP - 2437

EP - 2440

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 16

ER -

a-methylated derivatives of 2-arachidonyl glycerol: Synthesis, CB1 receptor activity and enzymatic stability

Abstrakti

Tutkimusalat

Pääsy asiakirjaan

SFX-saatavuus

Sormenjälki

Siteeraa tätä