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 -