C2-substituted quinazolinone derivatives exhibit A1 and/or A2A adenosine receptor affinities in the low micromolar range

化学 腺苷A2A受体 腺苷受体 腺苷 立体化学 受体 神经保护 喹啉酮 药理学 生物化学 兴奋剂 生物
作者
Lianie Pieterse,Mietha M. Van der Walt,Gisella Terre’Blanche
出处
期刊:Bioorganic & Medicinal Chemistry Letters [Elsevier BV]
卷期号:30 (16): 127274-127274 被引量:9
标识
DOI:10.1016/j.bmcl.2020.127274
摘要

Antagonists of the adenosine receptors (A1 and A2A subtypes) are widely researched as potential drug candidates for their role in Parkinson’s disease-related cognitive deficits (A1 subtype), motor dysfunction (A2A subtype) and to exhibit neuroprotective properties (A2A subtype). Previously the benzo-α-pyrone based derivative, 3-phenyl-1H-2-benzopyran-1-one, was found to display both A1 and A2A adenosine receptor affinity in the low micromolar range. Prompted by this, the α-pyrone core was structurally modified to explore related benzoxazinone and quinazolinone homologues previously unknown as adenosine receptor antagonists. Overall, the C2-substituted quinazolinone analogues displayed superior A1 and A2A adenosine receptor affinity over their C2-substituted benzoxazinone homologues. The benzoxazinones were devoid of A2A adenosine receptor binding, with only two compounds displaying A1 adenosine receptor affinity. In turn, the quinazolinones displayed varying degrees of affinity (low micromolar range) towards the A1 and A2A adenosine receptor subtypes. The highest A1 adenosine receptor affinity and selectivity were favoured by methyl para-substitution of phenyl ring B (A1Ki = 2.50 μM). On the other hand, 3,4-dimethoxy substitution of phenyl ring B afforded the best A2A adenosine receptor binding (A2AKi = 2.81 μM) among the quinazolinones investigated. In conclusion, the quinazolinones are ideal lead compounds for further structural optimization to gain improved adenosine receptor affinity, which may find therapeutic relevance in Parkinson’s disease-associated cognitive deficits and motor dysfunctions as well as exerting neuroprotective properties.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
青炀完成签到,获得积分10
2秒前
Jasper应助redisni采纳,获得10
2秒前
wangsiheng发布了新的文献求助10
3秒前
zh123完成签到,获得积分10
3秒前
5秒前
壮观的夏云完成签到,获得积分10
10秒前
10秒前
11秒前
可怜的游戏完成签到,获得积分10
12秒前
13秒前
17秒前
悦耳梦松发布了新的文献求助10
17秒前
我不是霍建华完成签到,获得积分10
18秒前
19秒前
19秒前
21秒前
桐桐应助火焰向上采纳,获得10
22秒前
24秒前
给我个二硫碘化钾完成签到,获得积分10
25秒前
迷路的晓旋完成签到,获得积分10
25秒前
wangsiheng完成签到,获得积分20
25秒前
zho发布了新的文献求助10
27秒前
28秒前
完美的鹤完成签到,获得积分10
29秒前
陈宇华发布了新的文献求助10
29秒前
conny完成签到,获得积分10
31秒前
32秒前
33秒前
超级柜子完成签到,获得积分10
33秒前
牛牛牛应助科研鸟采纳,获得10
34秒前
派先生完成签到,获得积分10
35秒前
悦耳梦松完成签到 ,获得积分10
36秒前
36秒前
欢呼的渊思完成签到,获得积分10
37秒前
1111111111111发布了新的文献求助10
38秒前
今夕是何年完成签到,获得积分10
39秒前
小鹿呀完成签到,获得积分10
40秒前
wy1693207859发布了新的文献求助10
41秒前
小立碗藓发布了新的文献求助10
41秒前
饱满的小霜完成签到,获得积分20
45秒前
高分求助中
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3963838
求助须知:如何正确求助?哪些是违规求助? 3509707
关于积分的说明 11148502
捐赠科研通 3243521
什么是DOI,文献DOI怎么找? 1792088
邀请新用户注册赠送积分活动 873506
科研通“疑难数据库(出版商)”最低求助积分说明 803808