4-isoxazolecarboxamide derivatives
    1.
    发明授权
    4-isoxazolecarboxamide derivatives 失效
    4-异恶唑甲酰胺衍生物

    公开(公告)号:US5001124A

    公开(公告)日:1991-03-19

    申请号:US474430

    申请日:1990-02-02

    摘要: This invention is directed to compounds of the formula (I): ##STR1## wherein R.sup.1 is --OR.sup.4 (where R.sup.4 is hydrogen, lower alkyl, lower hydroxyalkyl, phenyl, phenyl-lower-alkyl, or --(CH.sub.2).sub.n Y where n is an integer from 1 to 4 and Y is morpholino, -SR.sup.5, --C(O)OR.sup.5, --C(O)N(R.sup.6).sub.2, --N(R.sup.6).sub.2, or --N.sup.+ (R.sup.6).sub.3 X.sup.-, in which R.sup.5 is lower alkyl, each R.sup.6 is independently selected from hydrogen or lower alkyl, and X is halogen)or --SR.sup.7 (where R.sup.7 is lower alkyl, phenyl-lower-alkyl, or --(CH.sub.2).sub.n W where W is --N(R.sup.6).sub.2 or --N.sup.+ (R.sup.6).sub.3 X.sup.-, and n, R.sup.6 and X are as previously defined);R.sup.2 is lower alkyl, phenyl or phenyl-lower-alkyl;R.sup.3 is halo, hydroxy, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or --C(O)OR.sup.5 where R.sup.5 is as previously defined; andZ is a bond, 2,5-thienyl or 2,5-furanyl; or a pharmaceutically acceptable salt thereof. These compounds are useful in treating inflammation, autoimmune disease or allograft rejection in mammals.

    Benzopyridazinone and pyridopyridazinone compounds
    3.
    发明授权
    Benzopyridazinone and pyridopyridazinone compounds 失效
    苯并哒嗪酮和吡啶并哒嗪酮化合物

    公开(公告)号:US5716954A

    公开(公告)日:1998-02-10

    申请号:US369041

    申请日:1995-01-05

    摘要: Benzo or pyridopyridazinones and pyridazinthiones of the formula ##STR1## wherein: X and Y are nitrogen or carbon, provided that at least one is carbon, and Z is oxygen or sulfur; R.sup.1 is hydrogen, lower alkyl, aryl, aralkyl, heterocyclo, heterocyclo lower-alkyl, heteroaryl, or heteroaralkyl; R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently selected from hydrogen, lower alkyl, halo, carboxy, alkoxycarbonyl, carbamoyl, lower-alkyl carbonyl, halocarbonyl, thiomethyl, trifluoromethyl, cyano or nitro; or a pharmaceutically acceptable ester, ether or salt thereof, have been found to be useful as an anti-inflammatory, antasthmatic, immunosuppressive, anti-allograft rejection, anti-graft-vs-host rejection, autoimmune disease or analgetic agent(s).

    摘要翻译: 苯甲酸或吡啶并哒嗪酮和式哒嗪类化合物其中:X和Y是氮或碳,条件是至少一个是碳,Z是氧或硫; R 1是氢,低级烷基,芳基,芳烷基,杂环基,杂环低级烷基,杂芳基或杂芳烷基; R 2,R 3,R 4,R 5和R 6独立地选自氢,低级烷基,卤素,羧基,烷氧基羰基,氨基甲酰基,低级烷基羰基,卤代羰基,硫代甲基,三氟甲基,氰基或硝基。 或其药学上可接受的酯,醚或其盐可用作抗炎,抗哮喘,免疫抑制,抗同种异体移植物排斥,抗移植物抗宿主排斥反应,自身免疫疾病或止痛剂。

    Optionally substituted pyrido[2,3-d]pyridine-2,4(1H,3H)-diones and
pyrido[2,]pyrimidine-2(1H,3H)-ones
    4.
    发明授权
    Optionally substituted pyrido[2,3-d]pyridine-2,4(1H,3H)-diones and pyrido[2,]pyrimidine-2(1H,3H)-ones 失效
    取代吡啶并[2,3-d]吡啶-2,4(1H,3H) - 二酮和吡啶并[2,3-d]嘧啶-2(1H,3H) - 酮

    公开(公告)号:US5264437A

    公开(公告)日:1993-11-23

    申请号:US855179

    申请日:1992-03-20

    CPC分类号: C07D471/04 A61K31/505

    摘要: The present invention relates to optionally substituted pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones or optionally substituted pyrido[2,3-d]pyrimidine-2(1H,3H)-ones, i.e., compounds of Formula I: ##STR1## wherein: Y is --CH.sub.2 -- or --C(O)--;R.sup.1 is hydrogen or --(CH.sub.2).sub.n --R.sup.7, wherein:R.sup.7 is aryl or heteroaryl, andn is 1 or 2,provided that when Y is --C(O)--, R.sup.7 is heteroaryl; andR.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are hydrogen, or one is selected from lower alkyl, halo, carboxy, methoxycarbonyl, carbamoyl, methylcarbamoyl, di-methylcarbamoyl, methylcarbonyl, methylthio, methylsulfinyl, methylsulfonyl, hydroxymethyl, amino, trifluoromethyl, cyano or nitro; orR.sup.2, R.sup.3, R.sup.4 and R.sup.5 are independently selected from hydrogen, lower alkyl, nitro, chloro, fluoro, methoxycarbonyl or methylcarbonyl, provided at least one is hydrogen, and R.sup.6 is hydrogen;or a pharmaceutically acceptable ester, ether or salt thereof.

    摘要翻译: 本发明涉及任选取代的吡啶并[2,3-d]嘧啶-2,4(1H,3H) - 二酮或任选取代的吡啶并[2,3-d]嘧啶-2(1H,3H) - 酮,即 式I的化合物:其中:Y是-CH 2 - 或-C(O) - ; R 1是氢或 - (CH 2)n -R 7,其中:R 7是芳基或杂芳基,n是1或2,条件是当Y是-C(O) - 时,R 7是杂芳基; 并且R 2,R 3,R 4,R 5和R 6是氢,或者选自低级烷基,卤素,羧基,甲氧基羰基,氨基甲酰基,甲基氨基甲酰基,二 - 甲基氨基甲酰基,甲基羰基,甲硫基,甲基亚磺酰基,甲磺酰基,羟甲基,氨基, 或硝基; 或R 2,R 3,R 4和R 5独立地选自氢,低级烷基,硝基,氯,氟,甲氧基羰基或甲基羰基,条件是至少一个是氢,并且R 6是氢; 或其药学上可接受的酯,醚或其盐。

    Immunomodulation with novel pharmaceutical compositions
    5.
    发明授权
    Immunomodulation with novel pharmaceutical compositions 失效
    用新型药物组合物进行免疫调节

    公开(公告)号:US07388112B2

    公开(公告)日:2008-06-17

    申请号:US11171228

    申请日:2005-07-01

    摘要: The synthesis and use of a novel class of tumor necrosis factor (TNFα) inhibitors and immunomodulators are provided. Examples are those having the structures: wherein a, b and c are integers from 0 to 12, X equals NH or CHNH2, R1 and R2 each is a hydrogen or a C1 to C20 aliphatic; aliphatic amine; an alicyclic; aromatic; heterocycle; and halogenated forms thereof; and wherein, a, b and c are integers from 0 to 12; R1, R2, R3, and R4 each is a hydrogen or a C1 to C20; aliphatic amine; an alicyclic; aromatic; a heterocycle; and halogenated forms thereof.

    摘要翻译: 提供新型肿瘤坏死因子(TNFalpha)抑制剂和免疫调节剂的合成和使用。 实例是具有以下结构的那些:其中a,b和c是0至12的整数,X等于NH或CHNH 2,R 1和R 2, / SUB>各自为氢或C 1至C 20脂族基; 脂肪胺; 脂环族 芳香; 杂环 及其卤化形式; 并且其中a,b和c为0-12的整数; R 1,R 2,R 3和R 4各自为氢或C 1 -C 4烷基, 1至C 20; 脂肪胺; 脂环族 芳香; 杂环 及其卤化形式。

    Immunomodulation with novel pharmaceutical compositions
    6.
    发明授权
    Immunomodulation with novel pharmaceutical compositions 失效
    用新型药物组合物进行免疫调节

    公开(公告)号:US06919483B2

    公开(公告)日:2005-07-19

    申请号:US10443743

    申请日:2003-05-23

    摘要: The synthesis and use of a novel class of tumor necrosis factor (TNFα) inhibitors and immunomodulators are provided. These compounds have pharmacological applications as well as uses in assays relating to TNFα and other involved cytokines. As pharmaceuticals, these compounds are used to treat inflammatory, infectious, autoimmune or other proliferative diseases and conditions related to the unwanted presence or activity of TNFα and/or one or more other involved cytokines, alone or in combination with other agents. Examples of compounds of the present invention are those having the structures as shown below: wherein, a, b and c may be the same or different and are integers from 0 to 12, X equals NH or CHNH2, R1 and R2 can be the same or different and equal to a hydrogen or a straight or branched C1 to C20 saturated or unsaturated aliphatic; aliphatic amine; an alicyclic; single or multi-ring aromatic; a single or multi-ring aromatic heterocycle; a single or multi-ring saturated heterocycle and the halogenated forms thereof; and wherein, a, b and c may be the same or different and are integers from 0 to 12; R1, R2, R3, and R4 can be the same or different and equal to a hydrogen or a straight or branched C1 to C20 saturated or unsaturated aliphatic; aliphatic amine; an alicyclic; single or multi-ring aromatic; a single or multi-ring aromatic heterocycle; a single or multi-ring saturated heterocycle and the halogenated forms thereof.

    摘要翻译: 提供新型肿瘤坏死因子(TNFalpha)抑制剂和免疫调节剂的合成和使用。 这些化合物具有药理学应用以及与TNFα和其他涉及细胞因子相关的测定中的应用。 作为药物,这些化合物用于单独或与其它药剂组合治疗与TNFα和/或一种或多种其它涉及的细胞因子的不期望的存在或活性有关的炎性,感染性,自身免疫性或其它增殖性疾病和病症。 本发明化合物的实例是具有以下结构的那些:其中a,b和c可以相同或不同,为0-12的整数,X等于NH或CHNH 2 R 1和R 2可以相同或不同,并且等于氢或直链或支链C 1至C 1 - 20个饱和或不饱和脂肪族; 脂肪胺; 脂环族 单环或多环芳香族; 单环或多环芳族杂环; 单环或多环饱和杂环及其卤化形式; 并且其中a,b和c可以相同或不同,为0至12的整数; R 1,R 2,R 3和R 4可以相同或不同,并且等于 氢或直链或支链C 1至C 20饱和或不饱和脂族基; 脂肪胺; 脂环族 单环或多环芳香族; 单环或多环芳族杂环; 单环或多环饱和杂环及其卤化形式。

    4-isoxazolecarboxamide derivatives
    7.
    发明授权
    4-isoxazolecarboxamide derivatives 失效
    4-异恶唑甲酰胺衍生物

    公开(公告)号:US5328907A

    公开(公告)日:1994-07-12

    申请号:US818185

    申请日:1992-01-08

    摘要: This invention is directed to compounds of the formula (I): ##STR1## wherein R.sup.1 is --OR.sup.4 (where R.sup.4 is hydrogen, lower alkyl, lower hydroxyalkyl, phenyl, phenyl-lower-alkyl, or --(CH.sub.2).sub.n Y where n is an integer from 1 to 4 and Y is morpholino, --SR.sup.5, --C(O)OR.sup.5, --C(O)N(R.sup.6).sub.2, --N(R.sup.6).sub.2, or --N.sup.+ (R.sup.6).sub.3 X.sup.-, in which R.sup.5 is lower alkyl, each R.sup.6 is independently selected from hydrogen or lower alkyl, and X is halogen)or --SR.sup.7 (where R.sup.7 is lower alkyl, phenyl-lower-alkyl, or --(CH.sub.2).sub.n W whereW is --N(R.sup.6).sub.2 or --N.sup.+ (R.sup.6).sub.3 X.sup.-, and n, R.sup.6 and X are as previously defined);R.sup.2 is lower alkyl, phenyl or phenyl-lower-alkyl;R.sup.3 is halo, hydroxy, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or --C(O)OR.sup.5 where R.sup.5 is as previously defined; andZ is a bond, 2,5-thienyl or 2,5-furanyl;or a pharmaceutically acceptable salt thereof. These compounds are useful in treating inflammation, autoimmune disease or allograft rejection in mammals.

    摘要翻译: 本发明涉及式(I)的化合物:其中R 1是-OR 4(其中R 4是氢,低级烷基,低级羟烷基,苯基,苯基 - 低级烷基或 - (CH 2)n Y 其中n是1至4的整数,Y是吗啉代,-SR 5,-C(O)OR 5,-C(O)N(R 6)2,-N(R 6)2或-N + ,其中R 5是低级烷基,每个R 6独立地选自氢或低级烷基,X是卤素)或-SR 7(其中R 7是低级烷基,苯基 - 低级 - 烷基或 - (CH 2)n W,其中W是-N (R6)2或-N +(R6)3X-,n,R6和X如前定义); R2是低级烷基,苯基或苯基 - 低级 - 烷基; R 3是卤素,羟基,低级烷基,低级烷氧基,低级卤代烷基,低级卤代烷氧基或-C(O)OR 5,其中R 5如前所定义; Z为键,2,5-噻吩基或2,5-呋喃基; 或其药学上可接受的盐。 这些化合物可用于治疗哺乳动物的炎症,自身免疫性疾病或同种异体移植排斥反应。

    4-isoxazolecarboxamide derivatives
    8.
    发明授权
    4-isoxazolecarboxamide derivatives 失效
    4-异恶唑甲酰胺衍生物

    公开(公告)号:US5108999A

    公开(公告)日:1992-04-28

    申请号:US631181

    申请日:1990-12-19

    IPC分类号: C07D261/18 C07D413/12

    CPC分类号: C07D413/10 C07D261/18

    摘要: This invention is directed to compounds of the formula (I): ##STR1## wherein R.sup.1 is --OR.sup.4 (where R.sup.4 is hydrogen, lower alkyl, lower hydroxyalkyl, phenyl, phenyl-lower-alkyl, or --(CH.sub.2).sub.n Y where n is an integer from 1 to 4 and Y is morpholino, --SR.sup.5, --C(O)OR.sup.5, --C(O)N(R.sup.6).sub.2, --N(R.sup.6).sub.2, or --N.sup.+ (R.sup.6).sub.3 X.sup.-, in which R.sup.5 is lower alkyl, each R.sup.6 is independently selected from hydrogen or lower alkyl, and X is halogen) or --SR.sup.7 (where R.sup.7 is lower alkyl, phenyl-lower-alkyl, or --(CH.sub.2).sub.n W where W is --N(R.sup.6).sub.2 or --N.sup.+ (R.sup.6).sub.3 X.sup.-, and n, R.sup.6 and X are as previously defined);R.sup.2 is lower alkyl, phenyl or phenyl-lower-alkyl;R.sup.3 is halo, hydroxy, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or --C(O)OR.sup.5 where R.sup.5 is as previously defined; andZ is a bond, 2,5-thienyl or 2,5-furanyl; or a pharmaceutically acceptable salt thereof. These compounds are useful in treating inflammation, autoimmune disease or allograft rejection in mammals.

    摘要翻译: 本发明涉及式(I)的化合物:其中R 1是-OR 4(其中R 4是氢,低级烷基,低级羟烷基,苯基,苯基 - 低级烷基或 - (CH 2)n Y 其中n是1至4的整数,Y是吗啉代,-SR 5,-C(O)OR 5,-C(O)N(R 6)2,-N(R 6)2或-N + ,其中R 5是低级烷基,每个R 6独立地选自氢或低级烷基,X是卤素)或-SR 7(其中R 7是低级烷基,苯基 - 低级 - 烷基或 - (CH 2)n W,其中W是 - N(R6)2或-N +(R6)3X-,n,R6和X如前定义); R2是低级烷基,苯基或苯基 - 低级 - 烷基; R 3是卤素,羟基,低级烷基,低级烷氧基,低级卤代烷基,低级卤代烷氧基或-C(O)OR 5,其中R 5如前所定义; Z为键,2,5-噻吩基或2,5-呋喃基; 或其药学上可接受的盐。 这些化合物可用于治疗哺乳动物的炎症,自身免疫性疾病或同种异体移植排斥反应。