公开(公告)号：US5036107A

公开(公告)日：1991-07-30

申请号：US437165

申请日：1989-11-16

申请人： Waclaw J. Rzeszotarski ,  Maria E. Guzewska ,  Daniel W. McPherson ,  Ciro J. Spagnuolo ,  Kenneth J. Natalie, Jr.

发明人： Waclaw J. Rzeszotarski ,  Maria E. Guzewska ,  Daniel W. McPherson ,  Ciro J. Spagnuolo ,  Kenneth J. Natalie, Jr.

IPC分类号： C07D295/104

CPC分类号： C07D295/104 ,  Y10S514/906 ,  Y10S514/929 ,  Y10S514/93 ,  Y10S514/935

摘要： 1-Phenyl-7-substituted-hept-5-yn-2-ones substituted with a C.sub.1 to C.sub.7 alkyl, C.sub.3 to C.sub.6 cycloalkyl, aryl, heteroaryl or heterocycloalkyl group at the 1-position and an amino, a dialkylamino, a piperidyl, a pyrrolidyl or a hexahydroazepinyl group at the 7-position are disclosed which may have one or two substituents in addition to the phenyl group at the 1-position and also may have a p-fluoro substituent on the phenyl group. The preferred compounds are, 1-cyclohexyl-1-phenyl-1-hydroxy-7-dimethylaminohept-5-yn-2-one, 1-cyclobutyl-1-phenyl-1-hydroxy-7-dimethylaminohept-5-yn-2-one and 1-cyclo-1-phenyl-1-hydroxy-7-ethylaminohept-5-yn-2-one.The compounds are highly specific M.sub.1 -AChR antagonists with relatively prolonged duration of activity. They are particularly useful in the treatment of neurogenic bladder disorders and may be administered orally or parenterally in conventional formulations containing optional conventional additives such as binders, surfactants, emulsifiers, flavorants, preservatives and the like.

摘要翻译： 被1-取代的C1-C7烷基，C3至C6环烷基，芳基，杂芳基或杂环烷基取代的1-苯基-7-取代的庚-5-炔-2-酮和一个氨基，二烷基氨基，哌啶基 ，公开了7-位上的吡咯烷基或六氢氮杂基，除了在1-位上的苯基之外，还可以具有一个或两个取代基，并且在苯基上也可以具有对氟取代基。 优选的化合物是1-环己基-1-苯基-1-羟基-7-二甲基氨基庚基-5-炔-2-酮，1-环丁基-1-苯基-1-羟基-7-二甲基氨基庚基-5-炔-2 - 酮和1-环-1-苯基-1-羟基-7-乙基氨基庚-5-酮-2-酮。 这些化合物是具有较长活性持续时间的高度特异性的M1-AChR拮抗剂。 它们在治疗神经性膀胱疾病中特别有用，并且可以在含有任选的常规添加剂如粘合剂，表面活性剂，乳化剂，调味剂，防腐剂等的常规制剂中口服或肠胃外给药。

公开(公告)号：US4874600A

公开(公告)日：1989-10-17

申请号：US853105

申请日：1986-04-17

申请人： Daniel W. McPherson ,  Joanna S. Fowler ,  Alfred P. Wolf

发明人： Daniel W. McPherson ,  Joanna S. Fowler ,  Alfred P. Wolf

IPC分类号： A61K51/04

CPC分类号： A61K51/0406 ,  A61K2123/00

摘要： The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael addition of potassium .sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the .sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%.

摘要翻译： 本发明涉及一种新的放射性标记成像剂，无载体添加的[1-11C]腐胺，以及使用这种非常纯的材料作为放射性示踪剂，具有用于成像脑肿瘤的正电子发射断层扫描。 本发明还涉及基于将11C标记的氰化钾向丙烯腈中迈克尔加成，然后还原11C-标记的二腈，合成无载体添加的[1-11C]腐胺。 新方法快速有效，并提供具有大于1.4百分点/毫摩尔的比活性的放射性示踪剂，纯度大于95％。

公开(公告)号：US5001160A

公开(公告)日：1991-03-19

申请号：US372009

申请日：1989-06-27

申请人： Daniel W. McPherson ,  John P. Carter

发明人： Daniel W. McPherson ,  John P. Carter

IPC分类号： A61K31/495 ,  A61K20060101 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/54 ,  A61P1/04 ,  A61P11/08 ,  A61P13/02 ,  A61P15/00 ,  C07D20060101 ,  C07D295/10 ,  C07D295/104 ,  C07D295/12 ,  C07D295/125 ,  C07D295/20 ,  C07D307/52 ,  C07D317/58 ,  C07D333/20 ,  C07D401/06 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D413/06 ,  C07D417/06

CPC分类号： C07D295/104 ,  C07D295/125 ,  C07D307/52 ,  C07D317/58 ,  C07D333/20 ,  C07C2101/04 ,  C07C2101/14

摘要： Compounds are disclosed having the formula: ##STR1## in which R.sub.1 is a C.sub.1 l to C.sub.12 alkyl, said alkyl being straight or branched chain, saturated or unsaturated, monosubstituted or unsubstituted, said substituents being selected from piperidine, pyrrolidine, morpholine, thiomorpholine or cycloalkyl of 3 to 7 carbons, a cycloalkyl of 3 to 9 carbons, a lower alkylcycloalkyl of 4 to 9 carbons, or a polycycloalkyl of 2 to 3 rings containing 7 to 12 carbons;R.sub.2 is hydrogen, phenyl, phenyl singly or multiply substituted with halogen, hydroxy, lower alkoxy, methylene dioxy, nitro, lower alkyl or trifluoromethyl, lower alkyl, said alkyl being branched chain or straight, saturated, unsaturated, or cyclic and substituted or unsubstituted, said substituents being selected from thienyl, pyrrolyl, pyridyl, furanyl, hydroxy, lower alkoxy, or acetoxyalkyl wherein the alkyl group has 1 to 3 carbons, phenyl, phenyl substituted with halogen, hydroxy, lower alkoxy, lower alkyl, nitro, methylene dioxy or trifluoromethyl,Ph is phenyl or phenyl para-substituted by halogen, lower alkyl, lower alkoxy or trifluoromethyl; and the pharmaceutically acceptable nontoxic salts thereof.Pharmaceutical compositions containing the compounds and methods for the treatment of neurogenic bladder disorders are also disclosed. In the preferred compound Ph is phenyl, R.sub.1 is cyclobutyl and R.sub.2 is benzyl.

摘要翻译： 公开了具有下式的化合物：其中R1是C1-C12烷基，所述烷基是直链或支链，饱和或不饱和的，单取代或未取代的，所述取代基选自哌啶，吡咯烷，吗啉，硫代吗啉或 3至7个碳原子的环烷基，3至9个碳原子的环烷基，4至9个碳原子的低级烷基环烷基或2至3个含7至12个碳环的多环烷基; R 2是氢，苯基，被卤素，羟基，低级烷氧基，亚甲基二氧基，硝基，低级烷基或三氟甲基单或多取代的苯基，低级烷基，所述烷基是支链或直链，饱和的，不饱和的或环状的和取代或未取代的 所述取代基选自噻吩基，吡咯基，吡啶基，呋喃基，羟基，低级烷氧基或乙酰氧基烷基，其中烷基具有1至3个碳，苯基，被卤素取代的苯基，羟基，低级烷氧基，低级烷基，硝基，亚甲基二氧基 或三氟甲基，Ph为苯基或被卤素，低级烷基，低级烷氧基或三氟甲基取代的苯基; 及其药学上可接受的无毒盐。 还公开了含有化合物的药物组合物和治疗神经源性膀胱疾病的方法。 在优选的化合物中，Ph是苯基，R1是环丁基，R2是苄基。