89180-90-5Relevant academic research and scientific papers
2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG
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Paragraph 00825, (2016/07/05)
The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.
NITROGEN CONTAINING HETEROCYCLIC COMPOUNDS USEFUL AS M3-RECEPTOR MODULATORS
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Page/Page column 94, (2010/11/30)
A compound of formula (I): Formula (I) having M3 receptor- antagonist activity or having both muscarinic receptor antagonist and ss2-agonist activity; a composition comprising such a compound; the use of such a compound in therapy (such as asthma or COPD)
Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites
Glenn, Matthew P.,Chang, Sung-Youn,Hornéy, Carrie,Rivas, Kasey,Yokoyama, Kohei,Pusateri, Erin E.,Fletcher, Steven,Cummings, Christopher G.,Buckner, Frederick S.,Pendyala, Prakash R.,Chakrabarti, Debopam,Sebti, Sa?d M.,Gelb, Michael,Van Voorhis, Wesley C.,Hamilton, Andrew D.
, p. 5710 - 5727 (2007/10/03)
Third world nations require immediate access to inexpensive therapeutics to counter the high mortality inflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapies based on this recently validated antimalarial target. This novel series of compounds represents the first Plasmodium falciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitors displaying excellent in vitro activity (IC50 50 100 nM). Initial studies of absorption, metabolism, and oral bioavailability are reported.
COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA AND CANCER
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, (2008/06/13)
Formula (I): Where R1 is an optionally substituted C3-C12 hydrocarbyl group (preferably a cyclic alkyl group), an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R is a C(O)yR' group (preferably forming an optionally substituted C2-C5 acyl group), or a S(O)xR' group, where y is 0 or 1 and x is 0, 1 or 2 and R' is H or an optionally substituted C1-C12 alkyl group, or R' is an optionally substituted C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R5, R6, R7, R8, R9 and R10 are each independently selected from H, an optionally substituted C1-C12 hydrocarbyl group, including a C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group, or R5 and R6, R7 and R8 or R9 and R10 together form a keto (C=O) group; RN is H, an optionally substituted C1-C12 hydrocarbyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group, or an optionally substituted heteroaromatic group; A is Formula (II): a Formula (III): group, or a Formula (IV) or Formula (V) group, where Z is N, O or S; Ra is H, a C1-C12 optionally substituted hydrocarbyl group or an optionally substituted aromatic group; n is from 0 to 3; and pharmaceutically acceptable salts thereof. Compounds according to the invention are useful in one or more aspects to inhibit farnesyl transferase, or to treat malaria, neoplasia, a hyperproliferative disease state or arthritis, including rheumaroid arthritis or osteoarthritis.
Structurally simple farnesyltransferase inhibitors arrest the growth of malaria parasites
Glenn, Matthew P.,Chang, Sung-Youn,Hucke, Oliver,Verlinde, Christophe L. M. J.,Rivas, Kasey,Horney, Carrie,Yokoyama, Kohei,Buckner, Frederick S.,Pendyala, Prakash R.,Chakrabarti, Debopam,Gelb, Michael,Van Voorhis, Wesley C.,Sebti, Said M.,Hamilton, Andrew D.
, p. 4903 - 4906 (2007/10/03)
(Chemical Equation Presented) Antimalarial compounds: Structurally simple acyclic inhibitors of protein farnesyltransferase (active-site model shown) from the malaria parasite Plasmodium falciparum may allow third world countries access to an effective and inexpensive antimalarial therapy to counter the estimated half billion infections that occur annually.
