公开(公告)号：US5464852A

公开(公告)日：1995-11-07

申请号：US289113

申请日：1994-08-11

申请人： Richard P. Dunlap ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Lee H. Latimer ,  Chakrapani Subramanyam

发明人： Richard P. Dunlap ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Lee H. Latimer ,  Chakrapani Subramanyam

IPC分类号： C07D275/06 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07F9/6541 ,  A61K31/425 ,  A61K31/41 ,  C07D249/04

CPC分类号： C07D275/06 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07F9/6541

摘要： Compounds having the structural formula ##STR1## wherein L is N, O or SO.sub.n wherein n is 0, 1 or 2;L--R.sup.1 is a leaving group, H--L--R.sup.1 is the conjugate acid thereof and,when L is N, H--L--R.sup.1 has a pK.sub.a value less than or equal to 6, when L is O, H--L--R.sup.1 has a pK.sub.a value less than or equal to to 8, and when L is SO.sub.n, H--L--R.sup.1 has a pK.sub.a value less than or equal to 5;R.sup.2 is primary or secondary alkyl of two to four carbon atoms, primary alkylamino of one to three carbon atoms, primary alkylmethylamino of two to four carbon atoms, diethylamino or primary alkoxy of one to three carbon atoms; andR.sup.3 is from one to three of a variety of substituents at any or all of the 5-, 6- and 7-positions;or a pharmaceutically acceptable acid addition salt thereof if the compound has a basic functional group or a pharmaceutically acceptable base addition salt thereof if the compound has an acidic functional group,which inhibit the enzymatic activity of proteolytic enzymes, and processes for preparation thereof, method of use thereof in treatment of degenerative diseases and pharmaceutical compositions thereof are disclosed.

摘要翻译： 具有式I的结构式的化合物，其中L是N，O或SO，其中n是0,1或2; L-R1是离去基团，HL-R1是其共轭酸，当L为N时，HL-R1的pKa值小于或等于6，当L为O时，HL-R1的pKa值较小 在L为SOn时，HL-R1的pKa值小于等于5; R2是2至4个碳原子的伯或仲烷基，1至3个碳原子的伯烷基氨基，2至4个碳原子的伯烷基甲基氨基，1至3个碳原子的二乙氨基或伯烷氧基; 在任何或全部5-，6-和7-位上，R 3是1-3个各种取代基; 如果该化合物具有抑制蛋白水解酶的酶活性的酸性官能团，则该化合物具有碱性官能团或其药学上可接受的碱加成盐，或其药学上可接受的酸加成盐，及其制备方法， 公开了其在治疗退行性疾病中的用途及其药物组合物。

公开(公告)号：US5187173A

公开(公告)日：1993-02-16

申请号：US814741

申请日：1991-12-27

申请人： Ranjit C. Desai ,  John J. Court ,  Dennis J. Hlasta ,  Chakrapani Subramanyam

发明人： Ranjit C. Desai ,  John J. Court ,  Dennis J. Hlasta ,  Chakrapani Subramanyam

IPC分类号： A61K31/675 ,  A61K31/67 ,  A61P29/00 ,  C07D275/06 ,  C07D279/02 ,  C07F20060101 ,  C07F9/06 ,  C07F9/08 ,  C07F9/32 ,  C07F9/40 ,  C07F9/6541 ,  C07F9/6547 ,  C07F9/6558 ,  C07F9/6574

CPC分类号： C07F9/65583 ,  C07F9/6541 ,  C07F9/65742 ,  C07F9/65744

摘要： 4-R.sub.1 -R.sub.2 -R.sub.3 -2-Saccharinylmethyl, 4-R.sub.4 -4-R.sub.5 -6-R.sub.6 -4,5,6,7-tetrahydro-2-saccharinylmethyl and 4,7-C-4,5,6,7-tetrahydro-2-saccharinylmethyl phosphates, phosphonates and phosphinates of formulas I, II and IIA respectively herein, useful in the treatment of degenerative diseases, and compositions containing them, methods for using them to treat degenerative diseases, and processes for their preparation by reaction of the corresponding 2-halomethylsaccharins with a phosphate, phosphonate or phosphinic acid of formula III herein in the presence of an acid-acceptor.

公开(公告)号：US5128339A

公开(公告)日：1992-07-07

申请号：US782016

申请日：1991-10-24

申请人： Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Virendra Kumar ,  Chakrapani Subramanyam ,  Ranjit C. Desai ,  Dennis J. Hlasta ,  Manohar T. Saindane ,  Malcolm R. Bell ,  John J. Court

发明人： Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Virendra Kumar ,  Chakrapani Subramanyam ,  Ranjit C. Desai ,  Dennis J. Hlasta ,  Manohar T. Saindane ,  Malcolm R. Bell ,  John J. Court

IPC分类号： C07D275/06 ,  C07D417/04 ,  C07D417/12 ,  C07F9/6541

CPC分类号： C07D275/06 ,  C07D417/04 ,  C07D417/12 ,  C07F9/6541 ,  Y10S514/825 ,  Y10S514/851 ,  Y10S514/863

摘要： 4-R.sup.4 -R.sup.5 -2-Saccharinylmethyl aryl carboxylates, useful in the treatment of degenerative diseases, are prepared by reacting a 4-R.sup.4 -R.sup.5 -2-halomethylsaccharin with an arylcarboxylic acid in the presence of an acid-acceptor.

摘要翻译： 可用于治疗退行性疾病的4-R4-R5-2-糖基甲基芳基羧酸盐通过在酸 - 受体存在下使4-R 4 -R 5 - 2-卤代甲基糖精与芳基羧酸反应来制备。