75098-42-9Relevant articles and documents
HETEROCYCLIC COMPOUNDS USEFUL AS PDK1 INHIBITORS
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Page/Page column 88; 90, (2016/10/08)
The present invention provides compounds useful as inhibitors of PDK1. The present invention also provides compositions thereof, and methods of treating PDK1-mediated diseases.
PROCESSES FOR THE SYNTHESIS OF SUBSTITUTED UREA COMPOUNDS
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Page/Page column 41; 42, (2015/10/05)
The present invention concerns a process for preparing a compound having the Formula A; or a pharmaceutically acceptable salt or derivative thereof, or for preparing a substituted urea compound of Formula IIa, or a pharmaceutically acceptable salt or ester thereof, (Formula IIa) the process comprising the reaction of an imidazolyl intermediate of Formula IIa', with a carbamoyl halide of the formula: R1R2NC(=O)Hal, wherein Hal represents Cl, F, I or Br, wherein the intermediate of Formula IIa' is prepared by oxidation of the derivative of R5 and R6, R6-C(=O)CH2R5 to form a glyoxal intermediate R6-C(=O)(C=O)R5, which is subjected to treatment with ammonium hydroxide and an aldehyde R8CHO to provide the intermediate of Formula IIa', and wherein the compound substituents are as defined herein.
Targeting carnitine biosynthesis: Discovery of new inhibitors against γ-butyrobetaine hydroxylase
Tars, Kaspars,Leitans, Janis,Kazaks, Andris,Zelencova, Diana,Liepinsh, Edgars,Kuka, Janis,Makrecka, Marina,Lola, Daina,Andrianovs, Viktors,Gustina, Daina,Grinberga, Solveiga,Liepinsh, Edvards,Kalvinsh, Ivars,Dambrova, Maija,Loza, Einars,Pugovics, Osvalds
, p. 2213 - 2236 (2014/04/17)
γ-Butyrobetaine hydroxylase (BBOX) catalyzes the conversion of gamma butyrobetaine (GBB) to l-carnitine, which is involved in the generation of metabolic energy from long-chain fatty acids. BBOX inhibitor 3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propanoate (
UREA COMPOUNDS AND THEIR USE AS ENZYME INHIBITORS
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Page/Page column 30; 31, (2014/02/16)
A compound having the following structure: or a pharmaceutically acceptable salt or derivative thereof. The compound may be used in the treatment or prevention of a disorder selected from appetite regulation, obesity, metabolic disorders, cachexia, anorexia, pain, inflammation, neurotoxicity, neurotrauma, stroke, multiple sclerosis, spinal cord injury, Parkinson's disease, levodopa-induced dyskinesia, Huntington's disease, Gilles de la Tourette's syndrome, tardive dyskinesia, dystonia, amyotrophic lateral sclerosis, Alzheimer's disease, epilepsy, schizophrenia, anxiety, depression, insomnia, nausea, emesis, alcohol disorders, drug addictions such as opiates, nicotine, cocaine, alcohol and psychostimulants, hypertension, circulatory shock, myocardial reperfusion injury, atherosclerosis, asthma, glaucoma, retinopathy, cancer, inflammatory bowel disease, acute and chronic liver disease such as hepatitis and liver cirrhosis, arthritis and osteoporosis.
Selective κ-opioid agonists: Synthesis and structure-activity relationships of piperidines incorporating an oxo-containing acyl group
Giardina,Clarke,Dondio,Petrone,Sbacchi,Vecchietti
, p. 3482 - 3491 (2007/10/02)
This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2- (aminomethyl)piperidine derivatives, using κ-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their κ-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]- 1-[(5,6,7,8-tetrahydro-5-oxo-2-naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 μmol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective κ-agonists, has a reduced propensity to cause a number of κ-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 μmol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.
