60547-98-0Relevant articles and documents
BLOCKING TOLL-LIKE RECEPTOR 9 SIGNALING WITH SMALL MOLECULE ANTAGONIST
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, (2017/10/13)
The present invention relates to small molecule4-(piperazin-1-yl)quinazolin-2-amino compounds with formula (I) useful for inhibiting signalling by certain toll-like receptors (TLRs), especially TLR9. Toll-like receptors (TLRs) are members of the larger family of evolutionarily conserved pattern recognition receptors which are critical first line of defence for self-nonself discrimination by the host immune response. Aberrant TLR9 activation is implicated in autoreactive inflammation in different autoimmune diseases. The invention depicts compounds with formula (I), composition and methods can be used in a number of clinical applications, including as pharmaceutical agents and methods for treating conditions involving unwanted immune activity due to TLR9 activation.
QUINAZOLINE DERIVATIVES
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Page/Page column 30, (2010/02/11)
The invention relates to the use of compounds of the formula I: wherein: ring C is a 5-6 membered heterocyclic moiety; Z is -O-, -S-, or -CH2-; R1 is hydrogen, C1-4alkyl, C1-4alkoxymethyl, di(C1-4)alkoxy)methyl, C1-4alkanoyl, trifluoromethyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, carboxy, C3-7cycloalkyl, C3-7-cycloalkylC1-3alkyl, or an optionally substituted group selected from phenyl, benzyl, phenylC2-4alkyl and a 5-6 membered heterocyclic group; n is an integer from 0 to 5; m is an integer from 0 to 3; R2 represents hydrogen, hydroxy, halgeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NR3R4 (wherein R3 and R4, which may be the same or different, each represents hydrogen or C1-3alkyl), or R5X1- (wherein X1 represents a direct bond, -CH2-, or a heteroatom linker group and R5 is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R5 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Synthesis and identification of the major metabolites of prazosin formed in dog and rat
Althuis,Hess
, p. 146 - 149 (2007/10/05)
The 6 O demethyl and 7 O demethyl analogues of the new antihypertensive drug prazosin [2 [4 (2 furoyl) piperazin 1 yl] 4 amino 6,7 dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate ten step reaction sequences starting from isovanillin and vanillin, respectively. The 6 O demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7 O demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2 (1 piperazinyl) 4 amino 6,7 dimethoxyquinazoline and 2,4 diamino 6,7 dimethoxyquinazoline, are also described. All four metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.
