N-Monomethylation

In contrast to what was observed for DOM-like activity, N-monomethylation of AMPH-like agents does not decrease their AMPH-like character. Meth-AMPH (i.e., N-monomethylamphetamine) is slightly more potent than amphetamine likewise, methcathinone (N-monomethylcathinone) is twice as potent as cathinone. N-methylation of DOM-like agents does not convert... 

A comprehensive, randomized, placebo-controlled trial of infused bolus L-arg and its enantiomer (D-arg) included healthy subjects, non-insulin dependent diabetics, hypertensive subjects, and normotensives with primary hypercholesterolemia [147]. A blood-pressure drop and an acute inhibition of ADP-induced aggregation in platelet-rich plasma were observed in all subjects after L-arg administration (<5 g). Both responses to L-arg infusion closely correlated in magnitude, were weaker in noninsulin dependent diabetics and hypercholesterolemics, and declined with increasing age. Notably, D-arg did not elicit any of the L-arg effects, which were reduced by some 70% when superimposed upon ongoing, nonselective NOS inhibition with infused L-N-monomethyl-arginine (L-NMMA). Since D-arg is not a NOS substrate, and L-NMMA is a substrate-competitive NOS inhibitor, the L-arg effects observed in this study were theorized to reflect a rise in vascular NO production by eNOS. In contrast, the inhibition of platelet aggregation observed in vitro after a 5 min L-arg infusion (160 mg total dose) into healthy subjects and patients with angiographic... 

O. 016 mole of the amine and then 3.6 g of formaldehyde (ca. 10 ml of formalin) and reflux for 5 hours. Cool to room temperature, add 7 ml concentrated HCI and evaporate in vacuum. The resulting oily dimethylamine can be purified by dissolving in 25 ml water, extracting with 2X25 ml CHCI3. Basify the aqueous layer with 2N NaOH and extract with 3X25 ml ether, and proceed as described above for the N-methylamines. This procedure should work for both phenethylamines and phenylisopropylamines, and should affect the trip similarly to N-monomethylation. 

L-NMMA=N -monomethyl-L-arginine L-NAME=N -monomethyl-L-arginine LTP=long-term potentia-... 

Ramagopal, M. W., and Leighton, H. J. (1989). Effects of N -monomethyl-L-arginine on field stimulation-induced decreases in cytosolic Ca levels and relaxation in the rat anococcygeus muscle. Eur. J. Pharmacol. 174, 297-299. 

Toda, N., and Okamura, T. (1990a). Modification of L-N -monomethyl arginine (L-NMMA) of the response to nerve stimulation in isolated dog mesenteric and cerebral arteries. Jpn. J. Pharmacol. 52, 170-173. 

Bergmann, L., Kroncke, K.-D., Suschek, C., Kolb, H., and Kolb-Bachofern, V. (1992). Cytotoxic action of lL-1/3 against pancreatic islets is mediated via nitric oxide formation and is inhibited by N -monomethyl-L-arginine. FEES Lett. 299, 103-106. 

L-arginine analogues, such as N -monomethyl-L-arginine (Hibbs et al., 1987b), which acts as an extremely effective and competitive inhibitor of -NO formation. 

C. T Cell Cytokine Production in Presence and Absence of N°-Monomethyl-L-Arginine... 

Granger, D. L., Hibbs, J. B., Jr., and Broadnax, L. M. (1991). Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral N - -monomethyl-L-arginine.], Immunol. 146, 1294-1302. 

Mohrle and Mayer240,241 oxidized the 3-piperidinopropylamine (182) with mercuric acetate-EDTA reagent to obtain the pyrido[l,2-u]pyrimidine (184). Oxidation of the N-monomethyl and N,JV-dimethyl derivatives of 182 resulted in the N-methyl and A,A-dimethypiperidone derivatives of 185.241 If the reactions were carried out without the addition of EDTA, the perhydropyrido[l,2-a]pyrimidine(l83) and its N-methyl derivative also could be isolated from the reaction mixture.241 The pyrido[l,2-a]pyrimidine (184) was also prepared from the piperidone (186).242 The oxidative cyclization was successfully when applied to the piperidinopropionamides (187) to prepare the pyrido[l,2-a]pyrimidines(188) in addition to 2-oxopiperidino-propionamides.243... 

TheN-monomethylandtheN,N-dimethylhomologuesof2C-Dhavebeen synthesized from 2C-D. The N-monomethyl compound was obtained by the quatemization of the Schiff s base formed between 2C-D and benzaldehyde with methyl sulfate, followed by hydrolysis the hydrochloride salt had a melting point of 150-151 °C,fromEtOH. The N,N-dimethyl compound resulted from the action of formaldehyde-formic acid on 2C-D the hydrochloride salt had a melting point of 168-169 °C from EtOH/ether. These two compounds were some ten times less effective in interfering with conditioned responses in experimental rats. There is no report of their having been explored in man. 

The N-monomethylation of 12 to ismine (1) in 80% yield had been earlier reported [7]. The preponderance of N-norismine over the aminopyran 13 was attributed inter alia to the kinetically favoured 13-addition product 14 (Scheme 3) of the initial o radical to the proximate... 

Although the anodic generation of a cation in a-position to nigrogen in aliphatic amines is not difficult, this type of reaction is not always useful to the synthesis of alkaloidal compounds, since the cation is not stable and a simple dealkylation is the usual follow-up reaction. N-monomethyl and N,N-dimethylanilines are, however, useful starting materials for the synthesis of the skeleton of tetrahydroquinoline. The anodic methoxylation of N,N-dimethylaniline 20 takes place at the methyl group, and an iminium ion intermediate 22 is easily generated by treatment of the methoxylat-ed product 21 with Lewis add. This intermediate can be trapped in situ with a variety of nucleophiles such as electron-rich olefins yielding tetrahydroquinolines 23 16). 

The CHCs of the blow-fly Phormia regina are complex mixtures of saturated n-, monomethyl- and dimethylalkanes with 23-33 carbon atoms. These CHCs do not appear to change with age or diet, and differ only slightly between the sexes (Byrne et al, 1995 Stoffolano et al., 1997). Males show the same strong copulatory response to dummies covered with the extract of either sex but a very reduced response to hexane-washed flies (Stoffolano et al., 1997). In Calliphora vomitoria, the situation is less clear. Ablation of the female corpora allata or of the ovaries leads to an increase in the proportion of monomethylalkanes. However, these two procedures induce divergent effects on male attraction. Moreover, when hydrocarbon production was unchanged, male attraction was... 

For example the total pentane extracts of the web and cuticle from two European Agelenidae and Amaurobiidae comprised a complex mixture of fatty acids, alcohols and long-chain aliphatic hydrocarbons (Prouvost et al., 1999 Trabalon et al., 1996, 1997 Trabalon and Assi-Bessekon, 2008 Tables 16.1 and 16.2). The qualitative composition of cuticular extract obtained was similar to that reported for most insects and scorpions. Hydrocarbons in spiders form complex and varied mixtures with unsaturated hydrocarbons. In those species, the hydrocarbon fraction consists of n-, monomethyl- and... 

Figure 2 Stoichiometry of the enzymatic mechanism of formation of NO, and the structure of a competitive inhibitor, N -monomethyl-L-arginine (NMMA). NO is synthesized by all NOS s by a similar mechanism, involving the NADPH-dependent mixed-function oxidation of a guanidino nitrogen of the amino acid L-arginine (L-arg) to produce L-citrulline (L-cit) and -NO. The nonintegral stoichiometries are explained in the text. NMMA inhibits NOS as a competitive inhibitor...

SYNS -ACETYL-N -METHYL-4 -AiMINO-N,N-DIMETHYL-4-AMINOAZOBENZENE 4-(N-ACETYL-N-METHYL)AMINO-4 -(N, N -DIMETHYL. MINO)-AZO-BENZENE N, N -DIMETHYL-4 -AMINO-N-ACETYL-N-MONOMETHYL-4-AMINOAZOBEKZENE N-(4-((4-(DIMETHYL. MINO)PHENYL)AZO)PHENYL)-N-METHYLACETAMIDE... 

N, N -DIMETHYL-4 -AMINO-N-ACETYL-N-MONOMETHYL-4-A. nNOAZOBENZENE see DPQ200... 

All of the N-monomethyl derivatives of adenine, hypoxanthine, guanine, xanthine and uric acid have been synthesized. Several A -methylpurine derivatives were prepared by Traube himself, e.g. 1-methylguanine (1), or by the protocol of the Traube synthesis. ... 

Calver A, Collier J, Moncada S, Vallance P (1992) Effect of local infusion of N -monomethyl-L-arginine in patients with hypertension. The nitric oxide dilator mechanism appears abnormal J Hypertens 10 1025-1031. 

Heritac ndcaOedro K, LembowiczK, Pytel B (1991) N -monomethyl-L-arginine increases platdet deposition on danuiged endothdium in vivo. A scanning electron microscopy study Thromb Res 64 1-9. 

The fi-N-methyllysines are stable to acid hydrolysis and may be identified with the aid of an amino acid analyzer. With many routine analyzer systems e-N-monomethyl- and e-N-dimethyllysine elute as a shoulder or a partially resolved peak on the trailing edge of the lysine peak. If a 60 cm column is eluted with the buffer usually used for the 15 cm column these two methylated lysines are well resolved from lysine but not from each other. e-N-trimethyllysine usually elutes with lysine or slightly ahead of it in these systems (15 cm or 60 cm column eluted with pH 5.28 buffer). 

Benoiton et al. (1971) have found that lysine and s-N-monomethyl-lysine have similar 570/440 nm ratios after reaction with ninhydrin as measured with the analyzer, and that e-N-dimethyllysine and e-N-trimethyllysine also have similar 570/440 nm ratios, but the 570/440 nm ratios of the two pairs are different. This provided a method for estimating from the 570/440 nm ratio the content of e-N-monomethyl-lysine and e-N-dimethyllysine in hydrolysates that are analyzed in systems in which these two derivatives are not separated. For other analyzer systems that have been used to study methylated lysines, see the references cited above and also Deibler and Martenson (1973). 

Active metabolites may be much more important in iV,iV-dialkylated compounds that possess a j8-keto function, as in cathinone (2). In that case, the JV,iV-dimethyl compound is nearly as active as the N-monomethyl compound (142). It is known, however, that the... 

---