Norman Consulting, 18 Pink Lane, Burnham, Bucks, SL1 8JW,
Expert Opin Ther Pat. 2012 Nov;22(11):1377-83. doi: 10.1517/13543776.2012.718761. Epub 2012 Aug 23.
These two patent applications each claim combination formulations comprising a single dual-acting muscarinic antagonist/beta 2 agonist (MABA), as a free base or salt, with a second class of drug and the use of these formulations for the treatment of asthma and COPD. The two specified compounds are close analogues of each other and were originally disclosed in the same patent application. They are, respectively, 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)-N-cyclopentyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b]{1,4] oxazin-8-yl)ethylamino)ethyl)propanamide and N-butyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][l,4]oxazin-8-yl)ethylamino)ethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide.
这两项专利申请分别要求包含单一双重作用毒蕈碱拮抗剂/β2 激动剂（MABA）的组合配方的药物，其可以是游离碱或盐的形式，与第二药物类别联合使用，用于治疗哮喘和 COPD。这两种特定的化合物彼此非常相似，最初在同一项专利申请中披露。它们分别是 3-(2-氯-3-((4-(2-乙基噻唑-4-羰基)-1-氧杂-4,9-二氮杂螺[5.5]十一烷-9-基)甲基)苯乙氧基)-N-环戊基-N-(2-(2-(5-羟基-3-氧代-3,4-二氢-2H-苯并[b]{1,4}恶嗪-8-基)乙氨基)乙基)丙酰胺和 N-丁基-N-(2-(2-(5-羟基-3-氧代-3,4-二氢-2H-苯并[b][1,4]恶嗪-8-基)乙氨基)乙基)-3-(3-(2-(4-(2-异丙基噻唑-4-羰基)-1-氧杂-4,9-二氮杂螺[5.5]十一烷-9-基)乙基)苯乙氧基)丙酰胺。
