利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

87 条记录 (耗时 0.025 秒)

    PRO-DRUGS OF NSAIAS WITH VERY HIGH SKIN AND MEMBRANES PENETRATION RATES AND THEIR NEW MEDICINAL USES
    6.
    发明公开
    PRO-DRUGS OF NSAIAS WITH VERY HIGH SKIN AND MEMBRANES PENETRATION RATES AND THEIR NEW MEDICINAL USES 审中-公开
    NSAIDs的前体药物具有很高的皮肤和膜的普及率及新医疗用途

    公开(公告)号：EP2170826A1

    公开(公告)日：2010-04-07

    申请号：EP07825791.2

    申请日：2007-06-04

    申请人： Techfields Inc ,  Yu, Chongxi

    发明人： YU, Chongxi ,  XU, Lina

    IPC分类号： C07D209/32 ,  C07D231/12 ,  C07D471/08 ,  C07D487/08 ,  C07D213/74 ,  C07D215/10 ,  C07D217/12 ,  A61K31/44 ,  A61P29/00 ,  A61P3/00

    CPC分类号： C07D513/04 ,  C07D205/04 ,  C07D211/22 ,  C07D295/088 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D487/04 ,  C07D491/052

    摘要： The novel positively charged pro-drugs of NSAIAs in the general formulas (1, 2a, 2b, 2c, or 2d) 'Structure 1, 2a, 2b, 2c, or 2d' were designed and synthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) 'Structure 1, 2a, 2b, 2c, or 2d' indicated above can be prepared from metal salts, organic base salts, or immobilized base salts of NSAIAs with suitable halide compounds. The positively charged amino groups in the pro-drugs in this invention largely increase the solubility of the drugs in water and will bond to the negative charge on the phosphate head group of membrane. Thus, the local concentration of the outside of the membrane or skin will be very high and will facilitate the passage of these pro-drugs from a region of high concentration to a region of low concentration. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the pro-drug. When the molecules of membrane move, the membrane may 'crack' a little bit due to the bonding of the pro-drug. This will let the pro- drug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. W hen the amino group is not protonated, the bonding between the amino group of the pro-drug and the phosphate head group of the membrane will disassociate, and the pro-drug will enter the membrane completely. When the amino group of the pro-drug flips to the other side of the membrane and thus becomes protonated, then the pro-drug is pulled into the cytosol, a semi- liquid concentrated aqueous solution or suspension. These pro-drugs can be used for treating and preventing diabetes (type I or/and type II), abnormal blood glucose and lipid levels, stroke, heart attack, and other heart and vascular diseases Alzheimer's diseases, Parkinson's diseases and other neurodegenerative diseases, psoriasis, discoid lupus erythematosus, systemic lupus erythematosus (SLE), autoimmune hepatitis, multiple sclerosis (MS), and other autoimmune diseases, amyotrophic lateral sclerosis (ALS), oculopharyngeal muscular dystrophy ( OPMD), and other muscle disorders, inflamed hemorrhoids, cryptitis, other inflammatory conditions of the anorectum, and pruritus ani, prostatitis, prostatocystitis, varicose veins, autoimmune liver inflammation, autoimmune kidney inflammation, vein inflammation and other inflammations, skin cancers, breast cancer, colon-rectum cancer, oral cancer, and other cancers, scars, abnormal vascular skin lesions, birthmarks, moles (nevi), skin tags, aging spots (liver spots), and other skin disorders. These pro-drugs can be administered transdermally without the help of skin penetration enhancers.

    HYDRAZINE DERIVATIVES
    9.
    发明授权
    HYDRAZINE DERIVATIVES 失效
    HYDRAZINDERIVATE

    公开(公告)号：EP0993442B1

    公开(公告)日：2003-04-23

    申请号：EP98937498.8

    申请日：1998-06-18

    申请人： F. HOFFMANN-LA ROCHE AG

    发明人： BROADHURST, Michael John ,  JOHNSON, William, Henry ,  WALTER, Daryl, Simon

    IPC分类号： C07C311/49 ,  A61K31/18 ,  C07C259/06 ,  C07C281/02 ,  C07C281/06 ,  C07D209/32 ,  C07D209/48 ,  C07D211/58 ,  C07D211/98 ,  C07D213/42 ,  C07D213/56

    CPC分类号： C07D207/325 ,  C07C243/28 ,  C07C243/32 ,  C07C259/06 ,  C07C311/49 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D209/14 ,  C07D209/48 ,  C07D211/38 ,  C07D211/58 ,  C07D213/42 ,  C07D213/56 ,  C07D213/77 ,  C07D215/38 ,  C07D231/12 ,  C07D233/56 ,  C07D233/76 ,  C07D239/26 ,  C07D239/42 ,  C07D249/08 ,  C07D263/22 ,  C07D275/02 ,  C07D277/30 ,  C07D277/56 ,  C07D277/82 ,  C07D279/02 ,  C07D305/06 ,  C07D307/52 ,  C07D307/68 ,  C07D307/81 ,  C07D309/06 ,  C07D309/14 ,  C07D309/30 ,  C07D317/28 ,  C07D333/34 ,  C07D333/38 ,  C07D335/02 ,  Y10S514/837 ,  Y10S514/861 ,  Y10S514/863 ,  Y10S514/885 ,  Y10S514/903

    摘要： Hydrazine derivatives of formula (I) wherein Y signifies CO or SO2; R1 signifies lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2 signifies lower alkyl, halo-lower alkyl, aryl-lower alkyl, aryl-lower alkenyl or aryl when Y signifies SO¿2? and signifies lower alkyl, halo-lower alkyl, lower alkoxy, lower alkoxycarbonyl, acyl, lower cycloalkyl, aryl, aryl-lower alkyl, aryl-lower alkoxy or NR?5R6¿ when Y signifies CO; and R3 signifies hydrogen, lower alkyl optionally substituted by cyano, amino, hydroxy, lower alkoxy, lower alkoxycarbonly, heterocyclyl or heterocyclylcarbonyl, lower alkenyl, lower alkynyl, lower cycloalkyl, lower cycloalkyl- lower alkyl, aryl-lower alkyl, aryl-lower alkenyl, aryl or heterocyclyl; or R?2 and R3¿ together form the residue of a 5-, 6- or 7- membered cyclic amide, cyclic imide, cyclic sulphonamide or cyclic urethane group; R4 signifies lower alkyl, hydroxy-lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkly-lower alkyl or a grouping of the formula X-aryl, X-heteroaryl or -(CH¿2?)1-2-CH=CR?7R8¿; X signifies a spacer group; R?5 and R6¿ each individually signify hydrogen, lower alkyl or aryl-lower alkyl; and R?7 and R8¿ together represent a lower alkylene group in which one methylene group is optionally replaced by a hetero atom; and their pharmaceutically acceptable salts inhibit not only the release of tumour necrosis factor (TNF-α) and transforming growth factor (TGF-α) from cells, but also keratinocyte proliferation. They are useful as medicaments, especially for the treatment of inflammation, fever, haemorrhage, sepsis, rheumatoid arthritis, osteoarthritis, multiple sclerosis or psoriasis.

    摘要翻译： 甲酰亚胺Y的肼衍生物是CO或SO 2; R1是低级烷基，低级烯基，低级环烷基，低级环烷基 - 低级烷基，芳基或芳基 - 低级烷基; 当Y为SO2时，R2为低级烷基，卤代低级烷基，芳基 - 低级烷基，芳基 - 低级烯基或芳基，为低级烷基，卤代低级烷基，低级烷氧基，低级烷氧基羰基，酰基，低级环烷基，芳基， 当Y为CO时，低级烷基，芳基 - 低级烷氧基或NR5R6; 低级烯基，低级炔基，低级环烷基，低级环烷基 - 低级烷基，芳基 - 低级烷基，芳基 - 低级烯基，芳基 - 低级烷基，低级烷氧基，低级烷氧基，低级烷氧基， ，芳基或杂环基; 或R 2和R 3一起形成5-，6-或7-元环酰胺，环状酰亚胺，环状磺酰胺或环状氨基甲酸酯基团的残基; R4是低级烷基，羟基 - 低级烷基，低级烯基，低级环烷基，低级环烷基 - 低级烷基或式X-基，X-杂芳基或 - （CH2）1-2-CH = CR7R8基团; X是间隔基; R5和R6各自独立地为氢，低级烷基或芳基 - 低级烷基; 并且R 7和R 8一起代表一个亚甲基任选被杂原子取代的低级亚烷基; 并且其药学上可接受的盐不仅抑制肿瘤坏死因子（TNF-α）和转化生长因子（TGF-α）从细胞的释放，而且抑制角质形成细胞增殖。 它们可用作药物，特别是用于治疗炎症，发烧，出血，败血症，类风湿性关节炎，骨关节炎，多发性硬化或牛皮癣。