152148-79-3Relevant articles and documents
Reduction of the nitro group to amine by hydroiodic acid to synthesize o-aminophenol derivatives as putative degradative markers of neuromelanin
Wakamatsu, Kazumasa,Tanaka, Hitomi,Tabuchi, Keisuke,Ojika, Makoto,Zucca, Fabio A.,Zecca, Luigi,Ito, Shosuke
, p. 8039 - 8050 (2014/07/08)
Neuromelanin (NM) is produced in dopaminergic neurons of the substantia nigra (SN) and in noradrenergic neurons of the locus coeruleus (LC). The synthesis of NM in those neurons is a component of brain aging and there is the evidence that this pigment can be involved in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. NM is believed to derive from the oxidative polymerization of dopamine (DA) or norepinephrine (NE) with the participation of cysteine, dolichols and proteins. However, there are still unknown aspects in the chemical structure of NM from SN (SN-NM) and LC (LC-NM). In this study, we designed a new method to synthesize o-aminophenol compounds as putative degradation products of catecholamines and their metabolites which may be incorporated into NM. Those compounds are aminohydroxyphenylethylamine (AHPEA) isomers, aminohydroxyphenylacetic acid (AHPAA) isomers and aminohydroxyethylbenzene (AHEB) isomers, which are expected to arise from DA or NE, 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylmandelic acid (DOMA) and 3,4-dihydroxyphenylethanol (DOPE) or 3,4- dihydroxyphenylethyleneglycol (DOPEG), respectively. These o-aminophenol compounds were synthesized by the nitration of phenol derivatives followed by reduction with hydroiodic acid (HI), and they could be identified by HPLC in HI hydrolysates of SN-NM and LC-NM. This degradative approach by HI hydrolysis allows the identification of catecholic precursors unique to SN-NM and LC-NM, which are present in catecholaminergic neurons.
A novel and potent VLA-4 antagonist based on trans-4-substituted cyclohexanecarboxylic acid
Muro, Fumihito,Iimura, Shin,Yoneda, Yoshiyuki,Chiba, Jun,Watanabe, Toshiyuki,Setoguchi, Masaki,Takayama, Gensuke,Yokoyama, Mika,Takashi, Tohru,Nakayama, Atsushi,Machinaga, Nobuo
scheme or table, p. 1232 - 1243 (2009/08/15)
During the course of our study, it was revealed that the poor pharmacokinetic properties of a series of benzoic acid derivatives such as 1 should be attributed to the diphenylurea moiety. Thus, we replaced the diphenylurea moiety in 1 with a 2-(2-methylphenylamino)benzoxazole moiety which mimics the diphenylurea structure. However, this modification resulted in a significant decrease (3, IC50 = 19 nM) in VLA-4 inhibitory activity compared to 1 (IC50 = 1.6 nM). To address this discrepancy, we worked on optimization of the carboxylic acid moiety in compound 3. As a result, our efforts have led to the discovery of trans-4-substituted cyclohexanecarboxylic acid derivative 11b (IC50 = 2.8 nM) as a novel and potent VLA-4 antagonist. In addition, compound 11b exhibited favorable pharmacokinetic properties (CL = 3.3 ml/min/kg, F = 51%) in rats.
VLA-4 INHIBITORS
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, (2008/06/13)
The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
Chemical compounds
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, (2008/06/13)
Compound of formula (I) wherein: A is a bicyclic heteroaryl, optionally substituted with one or more substituents; B is linker group connecting group A to group D and comprising a 3 or 4 atom linker where each atom is independently selected from carbon, oxygen, nitrogen and sulphur and is optionally subsituted with one or more C1-6alkyl groups or two of such adjacent alkyl substituents may form a ring; C is aryl or a mono or bicyclic heteroaryl, each of which can be optionally substituted; D is an aryl or heteroaryl, both of which are optionally substituted R1is hydrogen, C1-5alkyl, C1-3alkanoyl or C1-3alkoxycarbonyl; R2to R5are each independently selected from hydrogen, C1-6alkyl, aryl and heteroaryl containing up to 2 heteroatoms chosen from oxygen, sulphur and nitrogen, the aryl and heteroaryl optionally substituted with C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-6alkylamino, C1-4alkylC1-6alkyoxyl, C1-6alkylaminoC1-6alkyl, nitro, cyano, halogeno, trifluoromethyl, hydroxy, (CH2)pOH where p is 1 or 2, —CO2Ra, and —CONRaRb, where Raand Rbare independently selected from hydrogen and C1-6alkyl or two of R2to R5can be taken together to form a 3 to 7 membered ring; R6is an acidic functional group; r and s are each independently 0 or 1 with the proviso that r and s cannot both be 0; or a pharmaceutically acceptable salt or in vivo hydrolysable derivative thereof.
Structure-activity studies for a novel series of N-(arylethyl)-N- (1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamines possessing dual 5- HT uptake inhibiting and α2-antagonistic activities
Meyer, Michael D.,Hancock, Arthur A.,Tietje, Karin,Sippy, Kevin B.,Prasad, Rajnandan,Stout, David M.,Arendsen, David L.,Donner, B. Greg,Carroll, William A.
, p. 1049 - 1062 (2007/10/03)
In search of an α2-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the α2-receptor (K(i) = 6.71 nM) and
