36716-69-5Relevant articles and documents
A convenient chemical-microbial method for developing fluorinated pharmaceuticals
Bright, Tara V.,Dalton, Fay,Elder, Victoria L.,Murphy, Cormac D.,O'Connor, Neil K.,Sandford, Graham
, p. 1135 - 1142 (2013)
A significant proportion of pharmaceuticals are fluorinated and selecting the site of fluorine incorporation can be an important beneficial part a drug development process. Here we describe initial experiments aimed at the development of a general method of selecting optimum sites on pro-drug molecules for fluorination, so that metabolic stability may be improved. Several model biphenyl derivatives were transformed by the fungus Cunninghamella elegans and the bacterium Streptomyces griseus, both of which contain cytochromes P450 that mimic oxidation processes in vivo, so that the site of oxidation could be determined. Subsequently, fluorinated biphenyl derivatives were synthesised using appropriate Suzuki-Miyaura coupling reactions, positioning the fluorine atom at the pre-determined site of microbial oxidation; the fluorinated biphenyl derivatives were incubated with the microorganisms and the degree of oxidation assessed. Biphenyl-4-carboxylic acid was transformed completely to 4′-hydroxybiphenyl-4-carboxylic acid by C. elegans but, in contrast, the 4′-fluoro-analogue remained untransformed exemplifying the microbial oxidation-chemical fluorination concept. 2′-Fluoro- and 3′-fluoro-biphenyl-4-carboxylic acid were also transformed, but more slowly than the non-fluorinated biphenyl carboxylic acid derivative. Thus, it is possible to design compounds in an iterative fashion with a longer metabolic half-life by identifying the sites that are most easily oxidised by in vitro methods and subsequent fluorination without recourse to extensive animal studies.
TRIAZOLOPYRIDINE ETHER DERIVATIVES AND THEIR USE IN NEUROLOGICAL AND PYSCHIATRIC DISORDERS
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Page/Page column 64, (2015/04/15)
The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds modulate the mGluR2 receptor and may be useful for the treatment of various disorders of the central nervous system.
Overcoming hERG activity in the discovery of a series of 4-azetidinyl-1-aryl-cyclohexanes as CCR2 antagonists
Zhang, Xuqing,Hufnagel, Heather,Markotan, Thomas,Lanter, James,Cai, Chaozhong,Hou, Cuifen,Singer, Monica,Opas, Evan,McKenney, Sandra,Crysler, Carl,Johnson, Dana,Sui, Zhihua
supporting information; experimental part, p. 5577 - 5582 (2011/10/09)
A series of 4-azetidinyl-1-aryl-cyclohexanes as potent CCR2 antagonists with high selectivity over activity for the hERG potassium channel is discovered through divergent SARs of CCR2 and hERG.
THIENOPYRIMIDINE AS CDC7 KINASE INHIBITORS
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Page/Page column 259, (2010/09/18)
The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer
OXOPIPERIDINE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
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Page/Page column 32, (2010/11/27)
The present invention relates to compounds of formula (I) as defined herein that are melanocortin receptor agonists, to the preparation thereof and to the therapeutic use thereof in the treatment or prevention of a condition selected from obesity, diabetes and sexual dysfunctions that can affect both sexes, in the treatment of cardiovascular diseases, and also in anti-inflammatory uses or in the treatment of alcohol dependency.
Development of a presynaptic 5-HT1A antagonist.
Mattson, Ronald J,Catt, John D,Sloan, Charles P,Gao,Carter, Richard B,Gentile, Anthony,Mahle, Cathy D,Matos, F Fatima,McGovern, Rachel,VanderMaelen, Cam P,Yocca, Frank D
, p. 285 - 288 (2007/10/03)
A new 5-HT(1A) silent antagonist 14 (5-HT(1A) IC(50)=2.2 nM) antagonizes the effects of agonists on reciprocal forepaw treading behavior, on neuronal firing in the rat dorsal raphe, and on 5-HT(1A) release in the raphe and hippocampus. While 14 alone was inactive in the social interaction paradigm, it completely reversed the social interaction activity of the serotonergic compounds (buspirone, 1, and 2).
Cyclohexylamine derivatives as subtype selective nmda receptor antagonists
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, (2008/06/13)
Described are cyclohexylamine derivatives of Formula (I), Formula (II) or Formula (III) and their pharmaceutically acceptable salts thereof. The compounds are antagonists of NMDA receptor channel complexes useful for treating cerebral vascular disorders such as, for example, cerebral ischemia, cardiac arrest, stroke, and Parkinson''s disease. The substituents are described in the specification. 1
Spiro and dispiro 1,2,4-trioxolane antimalarials
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, (2008/06/13)
A means and method for treating malaria using a spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl or spiropiperidyl ring on the other side of the trioxolane group, whereby the spirocyclohexyl ring is preferably functionalized or substituted at the 4-position or a spiropiperidyl ring that is functionalized or substituted at the nitrogen atom. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites.
Piperazinyl-cyclohexanes and cyclohexenes
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, (2008/06/13)
Novel non-dopaminergic antiischemic compounds have Formula I: wherein R=R1 and is independently H, C1-4 alky C1-4 alkoxy, C1-4 trihaloalkyl or halogen, or R and R1 may be taken together to form an -O(CH2)mO- (m=1 or 2); X=a 3-indolyl, phenyl, naphthalenyl or 2-benzothiazolyl residue; n=0, 1, 2 or 3; R2=R3 and is independently H or C1-4 alkyl; and R4=phenyl, 2-thienyl, 2-quinolinyl, 4-pyridinyl or substituted phenyl.
Alpha 1a adrenergic receptor antagonists
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, (2008/06/13)
This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.