公开(公告)号：US5310916A

公开(公告)日：1994-05-10

申请号：US572410

申请日：1990-08-24

申请人： Kenneth A. Jacobson ,  Gary L. Stiles ,  Daniel L. Boring

发明人： Kenneth A. Jacobson ,  Gary L. Stiles ,  Daniel L. Boring

IPC分类号： C07D473/06 ,  C07H19/16 ,  C07D331/00 ,  A61K31/505 ,  A61K31/52

CPC分类号： C07D473/06 ,  C07H19/16

摘要： Trifunctional agents useful as inhibitors of A.sub.1 -Adenosine receptors may be formulated into pharmaceutical compositions. These agents are represented by formula (I): ##STR1## wherein X is CH or N, R is an isothiocyanate group, an amino group or --NHCO.sub.2 C(CH.sub.3).sub.3 and R.sup.1 is hydrogen, carboxyl, lower alkoxycarbonyl, aminocarbonyl, ##STR2## lower alkyl, optionally substituted with: --OH, --COOH, lower ester of COOH, carboxamide, NHCOCH.sub.3, NHCOCH.sub.2 Br, halo, dimethylamino, triethylammonium, NHCONH.sub.2, SO.sub.2 NH.sub.2, --SO.sub.3 H, or a reporter group, particularly a spectroscopic reporter group such as a fluorescent dye, photoaffinity probe, or spin label probe, coupled through an amide, sulfonamide, amine or thiourea linkage, biotinylamino- (optionally containing an .epsilon.-aminocaproyl spacer chain or similar spacer chain) or; R.sup.1 is CONH--R.sup.2 or NHCSNH--R.sup.2, wherein R.sup.2 is lower alkyl, optionally substituted with: --OH, --COOH, lower ester of COOH, carboxamide, NHCOCH.sub.3, NHCOCH.sub.2 Br, halo, dimethylamino, triethylammonium, NHCONH.sub.2, SO.sub.2 NH.sub.2, --SO.sub.3 H, or a reporter group, particularly a spectroscopic reporter group such as a fluorescent dye, photoaffinity probe, or spin label probe, coupled through an amide, sulfonamide, amine, or thiourea linkage, biotinylamino- (optionally containing an .epsilon.-aminocaproyl spacer chain or similar spacer chain).

摘要翻译： 可用作A1-腺苷受体抑制剂的功能剂可以配制成药物组合物。 这些试剂由式（I）表示：其中X是CH或N，R是异硫氰酸酯基，氨基或-NHCO 2 C（CH 3）3，R 1是氢，羧基，低级烷氧基羰基 ，氨基羰基，低级烷基，任选被：-OH，-COOH，COOH的低级酯，羧酰胺，NHCOCH 3，NHCOCH 2 Br，卤素，二甲基氨基，三乙基铵，NHCONH 2，SO 2 NH 2，-SO 3 H或报道基团取代， 通过酰胺，磺酰胺，胺或硫脲键偶联的荧光染料，光亲和探针或自旋标记探针的光谱报告基团，生物素基氨基 - （任选地含有ε-氨基己酰基间隔链或类似的间隔链） R 1是CONH-R 2或NHCSNH-R 2，其中R 2是低级烷基，任选地被以下基团取代：-OH，-COOH，COOH的低级酯，甲酰胺，NHCOCH 3，NHCOCH 2 Br，卤素，二甲基氨基，三乙基铵，NHCONH 2，SO 2 NH 2，-SO 3 H， 或报告基团，特别是通过酰胺，磺酰胺，胺或硫脲键偶联的荧光染料，光亲和探针或自旋标记探针的光谱报道基团，生物素基氨基 - （任选地含有ε-氨基己酰基间隔链或类似物 间隔链）。

公开(公告)号：US5298508A

公开(公告)日：1994-03-29

申请号：US837105

申请日：1992-02-18

申请人： Kenneth A. Jacobson ,  Gary Stiles

发明人： Kenneth A. Jacobson ,  Gary Stiles

IPC分类号： C07D473/06 ,  C07H19/16 ,  A61K31/52 ,  A01N43/90 ,  C07D473/34

CPC分类号： C07H19/16 ,  C07D473/06

摘要： Irreversible ligands for adenosine receptors are derived from agonist and antagonist functionalized congeners which contain electrophilic acylating and alkylating groups for reaction at nucleophilic residues of adenosine receptors. The ligands are based on 8-aryl-substituted xanthines as antagonists and on N.sup.6 -substituted adenosine as agonists, wherein the electrophlic group may be, for example, isothiocyanate and N-hydroxysuccinimide esters.

摘要翻译： 腺苷受体的不可逆配体衍生自激动剂和拮抗剂官能化同系物，其含有用于腺苷受体亲核残基反应的亲电子酰化和烷基化基团。 配体基于作为拮抗剂的8-芳基取代的黄嘌呤和作为激动剂的N6-取代的腺苷，其中该亲电基团可以是例如异硫氰酸酯和N-羟基琥珀酰亚胺酯。

公开(公告)号：US5280015A

公开(公告)日：1994-01-18

申请号：US577528

申请日：1990-09-05

申请人： Kenneth A. Jacobson ,  R. Tyler McCabe ,  Phil Skolnick

发明人： Kenneth A. Jacobson ,  R. Tyler McCabe ,  Phil Skolnick

IPC分类号： C07H19/16 ,  A61K31/70 ,  C07H19/167

CPC分类号： A61K31/70 ,  C07H19/16

摘要： The present invention is directed to compounds useful as probes for characterizing and studying the adenosine A.sub.2 receptor. The present invention is also directed to methods of treating central nervous system disorders and cardiovascular disorders which include treating hypertension and thrombosis by administering said compounds.

摘要翻译： 本发明涉及可用作表征和研究腺苷A2受体的探针的化合物。 本发明还涉及治疗中枢神经系统疾病和心血管疾病的方法，其包括通过施用所述化合物治疗高血压和血栓形成。

公开(公告)号：US4696932A

公开(公告)日：1987-09-29

申请号：US717616

申请日：1985-03-29

申请人： Kenneth A. Jacobson ,  John W. Daly ,  Kenneth L. Kirk

发明人： Kenneth A. Jacobson ,  John W. Daly ,  Kenneth L. Kirk

IPC分类号： A61K38/00 ,  C07D473/06 ,  C07D473/08 ,  C07D519/00 ,  C07K5/06 ,  C07K5/065 ,  A61K31/52

CPC分类号： C07D473/06 ,  C07D473/08 ,  C07K5/06026 ,  C07K5/06078 ,  A61K38/00

摘要： Certain functionalized cogeners of 1,3-dialkylxanthine exhibit high potency and selectivity as antagonists for A.sub.1 - and A.sub.2 -adenosine receptors and are suitable for attachment to probes, drug carriers, or solid supports. These derivatives are characterized by the presence of a phenyl at the 8 position para-substituted with a functionalized chain to provide high water solubility and high receptor affinity. Some of these analogs, containing a distal amino- or carboxylic-functionalized chain, are suitable for synthesis of amino acid conjugates. The compounds of this invention are suitable for use as antiallergenic, antiasthmatic, or cardiotonic drugs, central nervous system stimulants, and diuretics.

摘要翻译： 某些功能化的1,3-二烷基黄嘌呤的同系物作为A1-和A2-腺苷受体的拮抗剂显示出高的效力和选择性，并且适于附着于探针，药物载体或固体支持物。 这些衍生物的特征在于在被官能化链对位取代的8位上存在苯基以提供高水溶性和高受体亲和力。 含有远端氨基或羧基官能化链的这些类似物中的一些适用于合成氨基酸缀合物。 本发明的化合物适合用作抗过敏，抗哮喘或强心药物，中枢神经系统兴奋剂和利尿剂。