Norman Consulting, 18 Pink Lane, Burnham, Buckinghamshire, SL1 8JW, UK.
Expert Opin Ther Pat. 2006 Sep;16(9):1321-6. doi: 10.1517/13543776.16.9.1321.
A series of 10 closely related patent applications define Theravance's approach to the development of long-acting M(3) selective antagonists for the treatment of chronic obstructive pulmonary disease. The applications illustrate a modular approach to the design of such agents, comprising a muscarinic pharmacophore attached to a second, less functionalised moiety via a variable length spacer incorporating heteroatoms. Eight of the applications utilise a a 4-piperidinylester of biphenylcarbamic acid as the muscarinic pharmacophore and two utilise 2,2-diphenyl-2-(S)-pyrrolidin-3-ylacetamide. The first group of eight applications encompasses the use of two tail groups and four different sets of linking groups, whereas the second uses two very different tail groups and different spacers.
一系列 10 项紧密相关的专利申请定义了 Theravance 公司开发长效 M(3)选择性拮抗剂治疗慢性阻塞性肺疾病的方法。这些申请展示了一种设计此类药物的模块化方法，包括通过包含杂原子的可变长度间隔物将毒蕈碱药效团连接到第二个功能较少的部分。八项申请使用联苯羰基双哌啶-4-基酯作为毒蕈碱药效团，两项申请使用 2,2-二苯基-2-(S)-吡咯烷-3-基乙酰胺。第一组八项申请包括使用两种尾部基团和四种不同的连接基团，而第二组使用两种非常不同的尾部基团和不同的间隔物。
