公开(公告)号：WO9503303A3

公开(公告)日：1995-03-02

申请号：PCT/GB9401543

申请日：1994-07-15

Applicant: KOSM GERALD EMMANUEL ,  ISRAEL STATE ,  FISHER ABRAHAM ,  KARTON YISHAI ,  MARCIANO DANIELE ,  BARAK DOV ,  MESHULAM HAIM

Inventor： FISHER ABRAHAM ,  KARTON YISHAI ,  MARCIANO DANIELE ,  BARAK DOV ,  MESHULAM HAIM

IPC: C07D487/10 ,  A61K31/42 ,  A61K31/425 ,  A61K31/435 ,  A61K31/438 ,  A61P25/00 ,  A61P25/04 ,  A61P25/18 ,  A61P25/28 ,  C07D453/02 ,  C07D471/10 ,  C07D471/20 ,  C07D491/10 ,  C07D497/10 ,  C07D498/10 ,  C07D498/20 ,  C07D513/10

CPC classification number: C07D471/10 ,  C07D491/10 ,  C07D497/10 ,  C07D513/10

Abstract: The invention relates to spiro compounds having central and peripheral nervous system activity, for example muscarinic agonist activity, having formulae (I, II, III, IV, V, VI, VII, VIII and IX) and their pharmaceutically acceptable salts, quaternary compounds which are structurally derived from said compounds having a tertiary nitrogen atom, enantiomers and racemates, wherein ring A together with the spiro-carbon atom constitutes a bridged or unbridged ring containing one or two ring nitrogen atoms, and the value of each of the other symbols in the formulae is defined.

公开(公告)号：WO9422483A3

公开(公告)日：1994-12-22

申请号：PCT/GB9400669

申请日：1994-03-30

Applicant: KOSM GERALD EMMANUEL ,  DPHARM LTD ,  KOZAK ALEXANDER

Inventor： KOZAK ALEXANDER

IPC: C12P17/18 ,  A61K31/19 ,  A61K31/215 ,  A61K31/47 ,  A61K31/66 ,  A61K31/70 ,  A61K38/00 ,  A61K45/00 ,  A61K47/48 ,  A61P43/00 ,  C07F9/10 ,  C07F9/62 ,  C07F9/6558 ,  C07F9/6561

CPC classification number: C07F9/10 ,  A61K47/54 ,  A61K47/542 ,  A61K47/544

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a human related to supranormal intracellular enzyme (.e.g. phospholipase and/or esterase) activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound accumulates selectively within cells having such supranormal intracellular enzyme activity. Exemplary conjugates are esters of the carboxylic function in the formula, with e.g. heptanoyl-sn-3-glycerophosphoryl-choline or octanoyl-sn-3-glycerophosphoryl-choline.

Abstract translation: 本发明涉及药学上可接受的前体药物，其是药理学活性化合物和细胞内运输佐剂的共价缀合物，其特征在于存在对细胞内酶活性具有断裂敏感性的共价键。 前药可用于治疗与超细胞内酶（“磷脂酶和/或酯酶”）活动相关的人的病症或疾病的技术，由此在将其施用于具有这种病症或疾病的人时，该结合被破坏 响应于这种活性，并且药理活性化合物选择性地在具有这种超常规细胞内酶活性的细胞内积累。 共轭物是式中羧基官能团的酯， 庚酰基-sn-3-甘油磷酰胆碱或辛酰基-sn-3-甘油磷酰胆碱。