小分子

小分子（英语：small molecule）是一个有机化学概念。一般将分子量小于900道尔顿的有机化合物分子称为小分子^[1]。小分子的直径以纳米计。目前大部分药物都是小分子类药物，蛋白质、核酸等生物大分子的基本组成单位（如氨基酸、核糖核苷酸、脱氧核苷酸）也是小分子。

小分子药物一般是抑制剂，通过干扰蛋白间相互作用起效^[2]。

药理学

目前大部分的药物都是小分子药物^[3] 。小分子的分子量上限一般设在900道尔顿。这是因为900道尔顿以下的分子在人体内能较快速地扩散进入细胞，到达作用靶点^[1]^[4]。根据里宾斯基五规则，口服给药的小分子药物的分子量最好能低于500道尔顿，否则损耗率会出现明显上升^[5]^[6]。

参见

参考资料

↑ ^1.0 ^1.1 Macielag MJ. Chemical properties of antibacterials and their uniqueness. Dougherty TJ, Pucci MJ (编). Antibiotic Discovery and Development. 2012: 801–2. ISBN 978-1-4614-1400-1. The majority of [oral] drugs from the general reference set have molecular weights below 550. In contrast the molecular-weight distribution of oral antibacterial agents is bimodal: 340–450 Da but with another group in the 700–900 molecular weight range.
↑ Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nature Reviews Drug Discovery. April 2004, 3 (4): 301–17. PMID 15060526. doi:10.1038/nrd1343.
↑ Samanen J. Chapter 5.2 How do SMDs differ from biomolecular drugs?. Ganellin CR, Jefferis R, Roberts SM (编). Introduction to Biological and Small Molecule Drug Research and Development: theory and case studies Kindle. New York: Academic Press. 2013: 161–203. ISBN 978-0-12-397176-0. doi:10.1016/B978-0-12-397176-0.00005-4. Table 5.13: Route of Administration: Small Molecules: oral administration usually possible; Biomolecules: Usually administered parenterally
↑ Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002, 45 (12): 2615–23. PMID 12036371. doi:10.1021/jm020017n.
↑ Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies. 2004, 1 (4): 337–341. PMID 24981612. doi:10.1016/j.ddtec.2004.11.007.
↑ Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews Drug Discovery. 2007, 6 (11): 881–90. PMID 17971784. doi:10.1038/nrd2445.

[Dougherty_Pucci_2012-1] 1.0 ^1.1 Macielag MJ. Chemical properties of antibacterials and their uniqueness. Dougherty TJ, Pucci MJ (编). Antibiotic Discovery and Development. 2012: 801–2. ISBN 978-1-4614-1400-1. The majority of [oral] drugs from the general reference set have molecular weights below 550. In contrast the molecular-weight distribution of oral antibacterial agents is bimodal: 340–450 Da but with another group in the 700–900 molecular weight range.

[pmid15060526-2] Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nature Reviews Drug Discovery. April 2004, 3 (4): 301–17. PMID 15060526. doi:10.1038/nrd1343.

[Ganellin_2013-3] Samanen J. Chapter 5.2 How do SMDs differ from biomolecular drugs?. Ganellin CR, Jefferis R, Roberts SM (编). Introduction to Biological and Small Molecule Drug Research and Development: theory and case studies Kindle. New York: Academic Press. 2013: 161–203. ISBN 978-0-12-397176-0. doi:10.1016/B978-0-12-397176-0.00005-4. Table 5.13: Route of Administration: Small Molecules: oral administration usually possible; Biomolecules: Usually administered parenterally

[pmid12036371-4] Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002, 45 (12): 2615–23. PMID 12036371. doi:10.1021/jm020017n.

[5] Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies. 2004, 1 (4): 337–341. PMID 24981612. doi:10.1016/j.ddtec.2004.11.007.

[pmid17971784-6] Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews Drug Discovery. 2007, 6 (11): 881–90. PMID 17971784. doi:10.1038/nrd2445.

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