Synthesis and analgesic activity of amines combining diazaadamantane and monoterpene fragments. / Ponomarev, Konstantin; Morozova, Ekaterina; Pavlova, Alla et al.
In: Medicinal Chemistry, Vol. 13, No. 8, 01.12.2017, p. 773-779.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Synthesis and analgesic activity of amines combining diazaadamantane and monoterpene fragments
AU - Ponomarev, Konstantin
AU - Morozova, Ekaterina
AU - Pavlova, Alla
AU - Suslov, Evgeniy
AU - Korchagina, Dina
AU - Nefedov, Andrej
AU - Tolstikova, Tat'yana
AU - Volcho, Konstantin
AU - Salakhutdinov, Nariman
N1 - Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Background: It was found earlier that compounds combining diazaadamantane and monoterpene moieties possessed promising analgesic activity along with low acute toxicity and the lack of ulcerogenic activity. Objective: In this paper, new structural analogues of the most active compounds were synthesized and evaluated for their analgesic activity. Methods: Their structures were confirmed by various analytical methods, such as 1H and13C NMR, HRMS. All of them were evaluated for analgesic activity at a dose of 20 mg/kg or less using acetic acid-induced writhing test and hot plate test. Results: Some compounds showed analgesic activity in acetic acid-induced writhing test. One of the synthesized compounds demonstrated high analgesic activity in both tests with 46% effect in acetic acid-induced writhing test and 89% effect in hot plate test. Both structural fragments of this compound did not possess any analgesic effect at a dose of 20 mg/kg. Conclusion: Structure-activity relationships indicated that the most active compound combines fragments of (–)-myrtenal and 6-amino-5,7-dimethyl-1,3-diazaadamantane. Both parts of the molecule are important for demonstrating analgesic activity.
AB - Background: It was found earlier that compounds combining diazaadamantane and monoterpene moieties possessed promising analgesic activity along with low acute toxicity and the lack of ulcerogenic activity. Objective: In this paper, new structural analogues of the most active compounds were synthesized and evaluated for their analgesic activity. Methods: Their structures were confirmed by various analytical methods, such as 1H and13C NMR, HRMS. All of them were evaluated for analgesic activity at a dose of 20 mg/kg or less using acetic acid-induced writhing test and hot plate test. Results: Some compounds showed analgesic activity in acetic acid-induced writhing test. One of the synthesized compounds demonstrated high analgesic activity in both tests with 46% effect in acetic acid-induced writhing test and 89% effect in hot plate test. Both structural fragments of this compound did not possess any analgesic effect at a dose of 20 mg/kg. Conclusion: Structure-activity relationships indicated that the most active compound combines fragments of (–)-myrtenal and 6-amino-5,7-dimethyl-1,3-diazaadamantane. Both parts of the molecule are important for demonstrating analgesic activity.
KW - Acetic acid-induced writhing test
KW - Adamantane
KW - Analgesic activity
KW - Azaadamantane
KW - Heterocyclic compounds
KW - Hot plate test
KW - Monoterpene
KW - Administration, Oral
KW - Monoterpenes/administration & dosage
KW - Pain/chemically induced
KW - Adamantane/administration & dosage
KW - Structure-Activity Relationship
KW - Amines/administration & dosage
KW - Dose-Response Relationship, Drug
KW - Acetic Acid
KW - Analgesics/administration & dosage
KW - Animals
KW - Mice
KW - Molecular Structure
KW - Pain Measurement
KW - azaadamantane
KW - PEPTIDASE-IV INHIBITOR
KW - adamantane
KW - analgesic activity
KW - DERIVATIVES
KW - POTENT
KW - acetic acid-induced writhing test
KW - hot plate test
KW - heterocyclic compounds
UR - http://www.scopus.com/inward/record.url?scp=85029551777&partnerID=8YFLogxK
U2 - 10.2174/1573406413666170525124316
DO - 10.2174/1573406413666170525124316
M3 - Article
C2 - 28545384
AN - SCOPUS:85029551777
VL - 13
SP - 773
EP - 779
JO - Medicinal Chemistry
JF - Medicinal Chemistry
SN - 1573-4064
IS - 8
ER -
ID: 9409327