1987 Fiscal Year Final Research Report Summary
Developmental studies of hypotensive adenosine derivatives
| Project/Area Number |
61870083
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
MATSUDA Akira Fac. of Pharmaceutical Sci., Hokkaido Univ., 薬学部, 助教授 (90157313)
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| Co-Investigator(Kenkyū-buntansha) |
OKAJIMA Fumikazu Fac. of Pharmaceutical Sci., Hokkaido Univ., 薬学部, 助手 (30142748)
MURAYAMA Toshihiko Fac. of Pharmaceutical Sci., Hokkaido Univ., 薬学部, 助手 (90174317)
UEDA Tohru Fac. of Pharmaceutical Sci., Hokkaido Univ., 薬学部, 教授 (00001032)
NOMURA Akihiko Fa. of Engineering, Fukui Univ., 工学部, 教授 (10001041)
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| Project Period (FY) |
1986 – 1987
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| Keywords | 2-Alkynyladenosine / Adenosine / Nucleoside / Hypotensive activity / Spontaneous hypertensive rat / Palladium catalyst / クロスカップリング |
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| Research Abstract |
Adenosine plays an important role in initiating numerous metabolic actions in variety of cells. These include many pharmacological activities. However, adenosine itself and its analogs have known to be metabolically unstable due to their deamination by adenosine deaminase and phosphorylation by adenosine kinase. From these, externally added adenosine is of duration in its action. In order to circumvent these disadvantages, numerous analogs of adenosine have been synthesized. Recently, We have found a convenient procedure for the introduction of alkynyl groups at the base portion of purine nucleosides. During the course of these synthetic studies we have found some pharmacological activites including antiallergic and hypotensive activites shown by 2-alkynyladenosines.
A various type of alkynylpurine nucleosides were synthesized from corresponding halogenated purine nucleosides by a palladium-catalyzed cross-coupling reaction with terminal alkynes. Among the series of the alynylated purine nucleosides, only 2-alkynyladenosines had a hypotensive activity. However, adenosines having shorter alkyl side-chains in the alkynyl group at 2-position showed a potent hypotensive activity accompanied by a decrease in heart rate following intravenous administration in normal rats. Interestingly, some of the 2-alkynyladenosines having longer alkyl side-chains showed a potent hypotensive activity without exhibiting a heart rate decrease. The latter compounds still have a hypotensive activity in the spontaneously hypertensive rat (SHR).
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