356790-62-0Relevant academic research and scientific papers
NOVEL IL-2/IL-15 RECEPTOR ANTAGONIST COMPOUNDS AND USES THEREOF FOR THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES OR GRAFT REJECTION
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, (2015/12/17)
Novel IL-2/IL-15 Receptor antagonist compounds and uses thereof for the treatment of autoimmune and inflammatory diseases or graft rejection Novel IL-2/IL-15 Receptor antagonist compounds and uses thereof for the treatment of autoimmune and inflammatory diseases or graft rejection. The invention relates to a compound of general formula (1) wherein X represents O, S or NR 4, wherein R4 is alkyl; A is selected from S, SO, SO2, NH and O; Y represents (CR5R6)n or (CR5 R6 O)n, wherein R5 and R6 identical or different are H or alkyl and n represents an integer from 1 to 15; R1 represents a 5 to 10 membered aromatic or non-aromatic mono-or bicyclic, 1 optionally bridged ring, R2 is C1-C4 alkyl; R3 is H or alkyl; p is 0 or 1; or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of the interactions of IL-2/15 to IL-2/15Rβand hence useful in the treatment of an autoimmune or an inflammatory diseases and graft rejection.
COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS
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, (2014/03/22)
Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound selectively inhibits a parasitic IMPDH versus a host IMPDH. Also disclosed are pharmaceutical compositions comprising one or more compounds of the invention. Related methods of treating various parasitic and bacterial infections in mammals are disclosed. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.
Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum
Johnson, Corey R.,Gorla, Suresh Kumar,Kavitha, Mandapati,Zhang, Minjia,Liu, Xiaoping,Striepen, Boris,Mead, Jan R.,Cuny, Gregory D.,Hedstrom, Lizbeth
, p. 1004 - 1007 (2013/03/13)
Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5′-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1- phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented.
Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening
Agrawal, Madhavi,Kharkar, Prashant,Moghe, Sonali,Mahajan, Tushar,Deka, Vaishali,Thakkar, Chandni,Nair, Amrutha,Mehta, Chirag,Bose, Julie,Kulkarni-Almeida, Asha,Bhedi, Dilip,Vishwakarma, Ram A.
, p. 5740 - 5743 (2013/10/01)
With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl- phthalazinone acetamide (7114863) increased glucose uptake (EC50 of 0.07 ± 0.02 μM) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-γ agonist activity thus making it a very interesting scaffold.
