4897-25-0Relevant articles and documents
Rational design of novel immunosuppressive drugs: Analogues of azathioprine lacking the 6-mercaptopurine substituent retain or have enhanced immunosuppressive effects
Crawford, Duncan J. K.,Maddocks, John L.,Jones, D. Neville,Szawlowski, Paul
, p. 2690 - 2695 (1996)
Clinical use of the immunosuppressive drug azathioprine is limited by potentially serious toxic effects related to depression of bone marrow function. The immunosuppressive and toxic properties of azathioprine are regarded as being properties of the cytotoxicity of its metabolite, 6- mercaptopurine (6-MP). However, azathioprine has an immunosuppressive effect additional to that attributable to 6-MP alone, and we propose that this is associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic immunosuppressants by replacing the 6-MP component of azathioprine with nontoxic thiols. We have synthesized and tested in vitro 24 such analogues, with two being further tested in vivo. In the human mixed lymphocyte reaction, virtually all compounds showed some degree of activity, 10 compounds being more active than azathioprine. In vivo, two compounds were more effective than azathioprine at prolonging graft survival in mice. In an oral toxicity study in male CD1 mice at doses equivalent to those at which azathioprine caused severe bone marrow depression both analogues had no toxic effects. Our results show that the immunosuppressive effects and bone marrow toxicity of azathioprine are not a consequence of release of 6-MP alone, and with appropriate modification can be separated, an approach which may lead to less toxic immunosuppressive drugs.
4,5-DIAMINOIMIDAZOLES AS NOVEL DEVELOPER-TYPE OXIDATION DYE PRECURSORS
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Paragraph 0277-0280, (2017/10/22)
An agent for oxidative changing of the color of keratin fibers, in particular human hair, includes, in a cosmetic support, as a developer-type oxidation dye precursor, at least one compound of formula (I) as further defined herein.
HETEROCYCLO-SUBSTITUTED IMIDAZOPYRAZINE PROTEIN TYROSINE KINASE INHIBITORS
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Page/Page column 39-40, (2009/06/27)
Novel heterocyclo-substituted imidazopyrazines and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic disorders.
ortho-Substituted azoles as selective and dual inhibitors of VEGF receptors 1 and 2
Kiselyov, Alexander S.,Piatnitski, Evgueni L.,Samet, Alexander V.,Kisliy, Victor P.,Semenov, Victor V.
, p. 1369 - 1375 (2007/10/03)
We have developed a series of novel potent ortho-substituted azole derivatives active against kinases VEGFR-1 and VEGFR-2. Both specific and dual ATP-competitive inhibitors of VEGFR-2 were identified. Kinase activity and selectivity could be controlled by varying the arylamido substituents at the azole ring. The most specific molecule (17) displayed >10-fold selectivity for VEGFR-2 over VEGFR-1. Compound activities in enzymatic and cell-based assays were in the range of activities for reported clinical and development candidates (IC50 30 × 10-5 cm/min) is indicative of their potential for intestinal absorption upon oral administration.
Hetaryl imidazoles: A novel dual inhibitors of VEGF receptors I and II
Kiselyov, Alexander S.,Semenova, Marina,Semenov, Victor V.
, p. 1440 - 1444 (2007/10/03)
A novel potent derivatives of hetaryl imidazoles were described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display VEGFR-2 inhibitory activity reaching IC50 100 nM in both enzymatic and cellular assays. The compounds also inhibit the related tyrosine kinase, VEGFR-1. By controlling the substitution pattern on the 5-carboxamido functionality, both dual and specific VEGFR-2 thiazoles were identified.
A New and Unequivocal Method for Establishing the Position of N-Glycosylation of Unsymmetrically C-Substituted Imidazoles
Benson, Timothy J.,Robinson, Brian
, p. 211 - 214 (2007/10/02)
N-Substitution of an unsymmetrically C-substituted imidazole can give rise to a pair of structurally isomeric derivatives and to differentiate between such related compounds can be difficult.Two methods, one spectroscopic and one chemical, for ascertaining the orientation of such N-substitutions are described, with particular application to the establishment of the direction of N-ribosidation of a series of halogeno nitroimidazoles.
NITROIMIDAZOLES. PART V. CHLORONITROIMIDAZOLES FROM DINITROIMIDAZOLES. A REINVESTIGATION
Suwinski, Jerzy,Salwinska, Ewa,Watras, Jan,Widel, Maria
, p. 1261 - 1272 (2007/10/02)
5(4)-Chloro-4(5)-nitroimidazole and 2-chloro-4(5)-nitroimidazole or their N-methyl derivatives have been synthesized in at least two independent routes.In contrast to some former reports it has been established that from 2,4(or 5)-dinitroimidazoles only 2-chloro-4(or 5)-nitroimidazoles are obtained.In 4,5-dinitroimidazoles only a nitro group in the 5-position is replaced by a chlorine atom.Structures of the obtained compounds have been confirmed by analyses of physico-chemical data.
