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    • 32. 发明授权
    • Method of treating diabetes with tissue-selective insulin analogs
    • 用组织选择性胰岛素类似物治疗糖尿病的方法
    • US5446020A
    • 1995-08-29
    • US81661
    • 1993-06-23
    • Robin J. AndyEric R. Larson
    • Robin J. AndyEric R. Larson
    • A61K38/00C07K14/62A61K37/26C07K7/00
    • C07K14/62A61K38/00Y10S514/866
    • Human insulin analogs are disclosed. These analogs are tissue-selective. Accordingly, pharmaceutical formulations containing the analogs of the invention provide superior clinical benefits as compared to human insulin when used in the treatment of patients suffering from diabetes. The analogs are modified at amino residue A12, A15 or A19, are different from the naturally occurring residue at said position, and are hepatoselective. Also disclosed are human insulin analogs modified at amino acid residues A12 or A14 or amino acid residues A10 and A13 different from naturally occurring residues or residues at said position or positions and are peripheral selective. DNA sequences and microorganisms comprising sequences coding for human insulin analogs are also provided. Processes for preparing the human insulin analogs are described.
    • 人胰岛素类似物被公开。 这些类似物是组织选择性的。 因此,当用于治疗患有糖尿病的患者时,与人胰岛素相比,含有本发明类似物的药物制剂提供了优异的临床益处。 类似物在氨基残基A12,A15或A19处被修饰,与所述位置处的天然存在的残基不同,并且是肝选择性的。 还公开了在氨基酸残基A12或A14处修饰的人胰岛素类似物或在所述位置或位置处与天然存在的残基或残基不同的氨基酸残基A10和A13,并且是周边选择性的。 还提供了包含编码人胰岛素类似物的序列的DNA序列和微生物。 描述了制备人胰岛素类似物的方法。
    • 34. 发明授权
    • Tissue-selective insulin analogs
    • 组织选择性胰岛素类似物
    • US5268453A
    • 1993-12-07
    • US918953
    • 1992-07-30
    • Robin J. AndyEric R. Larson
    • Robin J. AndyEric R. Larson
    • A61K38/00C07K14/62C07K7/00A61K37/26C12P21/06
    • C07K14/62A61K38/00Y10S514/866
    • Human insulin analogs are disclosed. These analogs are tissue-selective. Accordingly, pharmaceutical formulations containing the analogs of the invention provide superior clinical benefits as compared to human insulin when used in the treatment of patients suffering from diabetes. The analogs are modified at amino residue A12, A15 or A19, are different from the naturally occurring residue at said position, and are hepatoselective. Also disclosed are human insulin analogs modified at amino acid residues A12 or A14 or amino acid residues A10 and A13 different from naturally occurring residues or residues at said position or positions and are peripheral selective. DNA sequences and microorganisms comprising sequences coding for human insulin analogs are also provided. Processes for preparing the human insulin analogs are described.
    • 人胰岛素类似物被公开。 这些类似物是组织选择性的。 因此,当用于治疗患有糖尿病的患者时,与人胰岛素相比,含有本发明类似物的药物制剂提供了优异的临床益处。 类似物在氨基残基A12,A15或A19处被修饰,与所述位置处的天然存在的残基不同,并且是肝选择性的。 还公开了在氨基酸残基A12或A14处修饰的人胰岛素类似物或在所述位置或位置处与天然存在的残基或残基不同的氨基酸残基A10和A13,并且是周边选择性的。 还提供了包含编码人胰岛素类似物的序列的DNA序列和微生物。 描述了制备人胰岛素类似物的方法。
    • 38. 发明授权
    • Azacyclic-heterocyclic compounds as angiotension II receptor antagonists
    • 偶氮环杂环化合物作为血管紧张素II受体拮抗剂
    • US5789415A
    • 1998-08-04
    • US569133
    • 1996-01-11
    • Philip A. CarpinoEric R. LarsonBanavara L. Mylari
    • Philip A. CarpinoEric R. LarsonBanavara L. Mylari
    • A61K31/00C07D401/06C07D405/00C07D409/06C07D471/04A61K31/44A61K31/505C07D403/12C07D403/14
    • C07D401/06C07D409/06C07D471/04
    • Compounds of the formula ##STR1## wherein: Q is naphthyl, heterocyclic or heterobicyclic; R.sup.1 and R.sup.2, when taken separately, are hydrogen, hydroxy, alkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenyl, heterocyclic or heterobicyclic; R.sup.1 and R.sup.2, when taken together, form a carbocyclic, carbobicyclic, heterocyclic or heterobicyclic group; R.sup.3 is --(CH.sub.2).sub.n COR.sup.4, tetrazolyl, alkyltetrazolyl, triazolyl, alkyltriazolyl, --(CH.sub.2).sub.n CH.sub.2 OH, --SO.sub.2 R.sup.4, --SO.sub.2 NR.sup.5 R.sup.6 or --NHSO.sub.2 R.sup.7 ; R.sup.4 is hydrogen, hydroxy, --NR.sup.5 R.sup.6, --NHSO.sub.2 R.sup.7, alkoxy, alkylthio, --NR.sup.5 R.sup.6, --NHSO.sub.2 R.sup.7 or --OY; n is 0 to 5; Y is a pharmaceutically acceptable cation or a group hydrolyzable under physiological conditions; R.sup.5 and R.sup.6, when taken separately, are hydrogen, alkyl, --CONRR, --COOR or --CO(C.sub.6 H.sub.5); R.sup.5 and R.sup.6, when taken together, form an azacyclic ring; R.sup.7 is alkyl or phenyl; each R is hydrogen or alkyl and X is an azacyclic or azabicyclic group, inhibit angiotensin II in mammals and are useful in treating conditions such as hypertension, congestive heart failure and glaucoma and as the active ingredient in pharmaceutical compositions for treating such conditions.
    • PCT No.PCT / IB94 / 00187 Sec。 371日期1996年1月11日 102(e)日期1996年1月11日PCT 1994年7月1日PCT公布。 公开号WO95 / 02596 日期1995年1月26日化学式的化合物,其中:Q为萘基,杂环或杂双环; R1和R2分别为氢,羟基,烷基,烷硫基,烷基亚磺酰基,烷基磺酰基,苯基,杂环或杂双环; 当R1和R2一起形成碳环,碳双环,杂环或杂双环基团时; R3是 - (CH2)nCOR4,四唑基,烷基四唑基,三唑基,烷基三唑基, - (CH2)nCH2OH,-SO2R4,-SO2NR5R6或-NHSO2R7; R4是氢,羟基,-NR5R6,-NHSO2R7,烷氧基,烷硫基,-NR5R6,-NHSO2R7或-OY; n为0〜5; Y是药学上可接受的阳离子或在生理条件下可水解的基团; R5和R6分别为氢,烷基,-CONRR,-COOR或-CO(C6H5); 当R 5和R 6一起形成氮杂环时, R7是烷基或苯基; 每个R是氢或烷基,X是氮杂环或氮杂双环基,在哺乳动物中抑制血管紧张素II,并且可用于治疗诸如高血压,充血性心力衰竭和青光眼的病症,并且作为用于治疗这种病症的药物组合物中的活性成分。