- Identification of novel thiazolo[5,4-b]pyridine derivatives as potent phosphoinositide 3-kinase inhibitors
-
A series of novel 2-pyridyl, 4-morpholinyl substituted thiazolo[5,4-b]pyridine analogues have been designed and synthesized in this paper. These thiazolo[5,4-b]pyridines were efficiently prepared in seven steps from commercially available substances in mo
- Dong, Yi,Lin, Songwen,Tian, Hua,Xia, Liang,Xu, Heng,Zhang, Jingbo,Zhang, Kehui,Zhang, Yan
-
-
Read Online
- Substituted arylsulphonamides as inhibitors of perforin-mediated lysis
-
The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection.
- Spicer, Julie A.,Miller, Christian K.,O'Connor, Patrick D.,Jose, Jiney,Huttunen, Kristiina M.,Jaiswal, Jagdish K.,Denny, William A.,Akhlaghi, Hedieh,Browne, Kylie A.,Trapani, Joseph A.
-
p. 139 - 155
(2017/06/07)
-
- Benzenesulphonamide inhibitors of the cytolytic protein perforin
-
The pore-forming protein perforin is a key component of mammalian cell-mediated immunity and essential to the pathway that allows elimination of virus-infected and transformed cells. Perforin activity has also been implicated in certain auto-immune conditions and therapy-induced conditions such as allograft rejection and graft versus host disease. An inhibitor of perforin activity could be used as a highly specific immunosuppressive treatment for these conditions, with reduced side-effects compared to currently accepted therapies. Previously identified first-in-class inhibitors based on a 2-thioxoimidazolidin-4-one core show suboptimal physicochemical properties and toxicity toward the natural killer (NK) cells that secrete perforin in vivo. The current benzenesulphonamide-based series delivers a non-toxic bioisosteric replacement possessing improved solubility.
- Spicer, Julie A.,Miller, Christian K.,O'Connor, Patrick D.,Jose, Jiney,Huttunen, Kristiina M.,Jaiswal, Jagdish K.,Denny, William A.,Akhlaghi, Hedieh,Browne, Kylie A.,Trapani, Joseph A.
-
supporting information
p. 1050 - 1054
(2017/09/30)
-
- NOVEL PYRIDOPYRIMIDINE DERIVATIVES AND USE THEREOF
-
The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.
- -
-
Page/Page column 18
(2012/09/25)
-
- PYRIDOPYRIMIDINE DERIVATIVES AS PI3 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of PB kinases using pyridoprimidine derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of pyridopyrimidine derivatives.
- -
-
Page/Page column 51
(2009/04/25)
-
- QUINAZOLINE DERIVATIVES AS PI3 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of P13 kinases using quinazoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinazoline derivatives.
- -
-
Page/Page column 76-77
(2009/01/23)
-
- NAPHTHYRIDINE, DERIVATIVES AS P13 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of PB kinases using naphthyridine derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of naphthyridine derivatives.
- -
-
Page/Page column 75
(2009/01/24)
-
- QUINOXALINE DERIVATIVES AS PI3 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of PI3 kinases using quinoxaline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinoxaline derivatives.
- -
-
Page/Page column 87-88
(2009/01/20)
-