Central nervous system activity

The methoxy derivative 536, prepared from the aminoquinolone, was transformed into 537. Selective hydrolysis of 537 gave 538 which was treated with COCI2 followed by MeONH2 HCl to afford 539 that was cyclized upon treatment with PhI(OCOCF3)2 to give 540. Deprotection with K2CO3 afforded 541 which had central nervous system activity (95WOP9504056) (Scheme 91). 

Derivatives 82 (R=cycloalkyl) proved to be central nervous system stimulants, whereas 3-alkyl analogs were claimed as vasodepressant or hypotensive agents with some residual central nervous system activity [139, 154]. 

Jamieson DD, Duffield PH, Cheng D, Duffield AM. (1989). Comparison of the central nervous system activity of the aqueous and lipid extract of kava (Piper methysticum). Arch Int Pharmacodyn Ther. Sept.-Oct. 301 66-80. 

Teissier E, Fennrich S, Strazielle N, Daval JL, Ray D, et al. 1998. Drug metabolism in in vitro organotypic and cellular models of mammalian central nervous system activities of membrane-bound epoxide hydrolase and NADPH-cytochrome P-450 (c) reductase. Neurotoxicology 19 347-355. 

Clonidine and other imidazoline compounds have also been shown to reduce muscle spasms by their central nervous system activity. Tizanidine is perhaps the most thoroughly studied clonidine analog. It is an agonist at a2-adrenergic receptors, but reduces spasticity at doses that result in significantly less hypotension than clonidine. 

The direct condensation of unsaturated oxazolones with tryptamine in hydrochloric acid is an important and interesting case that deserves special attention. The reaction occurs via in situ hydrolysis of the oxazolone to a keto acid followed by a Pictet-Spengler-like reaction with tryptamine. This protocol affords a tetrahydro-p-carboline wherein the oxazolone is the synthetic equivalent of an arylacetalde-hyde. The reaction has been extended to substituted tryptamines 500 thus, allowing access to 1,3,4-trisubstituted tetrahydro-p-carbolines 501 as shown in Scheme 7.159. Some of these compounds have shown promising central nervous system activity. 

Eleutherococcus senticosus (Rupr. ex Maxim.) Maxim. Ci Wu Jia (Siberian ginseng) (bark, root) Eleutherosides, beta-sitosterol glucoside, 1-sesamen, syringareinol.7-33 Central nervous system activating and antistress action. 

Radiolabelled compounds for the histamine H3 receptor have been proven to be of great value in pharmacological and biochemical research. Some iodinated and tritiated compounds haven become standard research tools. In contrast, the development of PET or SPECT ligands has been proven to be troublesome. So far there has been no radiolabelled compound which is taken up into the brain in reasonable amounts to allow for PET or SPECT studies of the H3 receptor in the brain. The search for new radiolabelled compounds is still going on however, as is research to find out why these radiolabelled compounds do not enter the brain as opposed to their non-radiolabelled equivalents. One can detect pharmacological effects which can only be caused by central nervous system activity of these non-radiolabelled compounds. In view of the... 

The first identified cannabinoid receptor subtype, CB was cloned and demonstrated to have an amino acid sequence consistent with a tertiary structure typical of the seven transmembrane-spanning proteins that are coupled to G proteins. In addition to being found in the central nervous system, mRNA for CB has also been identified in testes. The central nervous system responses to cannabinoid compounds are believed to be mediated exclusively by CB, inasmuch as CB2 transcripts could not be found in brain tissue by either Northern analysis or in situ hybridization studies. CBj transduces signals in response to central-nervous-system-active constituents of C. sativa as well as synthetic bicyclic and tricyclic cannabinoid analogs, aminoalkylindole, and eicosanoid cannabimimetic compounds. CB is coupled to G, to inhibit adenylate cyclase activity and to a pertussis-sensitive G protein to regulate Ca2+ currents. 

The chemical formula referred to in claim 1 is also known as amitriptyline, and its chemical structure is given in Figure 8.13, along with the chemical structure of imipramineused as an antidepressant and additional prior art compounds having central nervous system activity from which the method of claim 1 was deemed obvious. 

The preliminary biological studies on isolated Heimia alkaloids did not confirm any central nervous system activity in rats (4). Later biological... 

Ensrud KE, Blackwell T, Mangione CM, Bowman PJ, Bauer DC, Schwartz A, Hanlon JT, Nevitt MC, Whooley MA. Central nervous system active medications and risk for fractures in older women. Arch Intern Med 2003 163 949-57. 

Efficient preparation of dicarboxylic acid 1275 <2001J(P1)1039> was the starting point of the novel, convenient synthesis of a known, central nervous system active 8-chloro-4//,6//-pyrrolo[l,2- r][4,IJbenzoxazepine 1276 (Equation 281). In the two-step synthesis the dicarboxylic acid 1275 was reduced to the diol, then this was treated with silica gel. Silica is acidic enough to promote elimination of water under mild conditions. In this way, compound 1276 could be prepared conveniently while the known methods (use of P2O5 or other strong acid) initiate serious side reactions of the pyrrole moiety. 

Said SI, Berisha HI, Pakbaz H (1995) Al-methyl-D-aspartate receptors outside the central nervous system activation causes acute lung injury that is mediated by nitric oxide synthesis and prevented by vasoactive intestinal peptide. Neuroscience 65 943-946. 

Lee CM, Michaels RJ, Zaugg HE, Dren AT, Plotnikoff NP, Young PR (1977) Cannabinoids. Synthesis and central nervous system activity of 8-substituted 10-hydroxy-5,5-dimethyl-5H-[ l]benzopyrano[4,3-c]pyridine and derivatives. J Med Chem 20 1508-1511... 

Matsumoto K, Stark P, Meister RG (1977b) Synthesis and central nervous system activities of some B-ring homocannabinoid derivatives and related lactones. J Med Chem 20 25-30... 

CNS Predicted central nervous system activity on a —2 (inactive) to 2 (active) scale... 

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