Showing papers on "Hydrobromide published in 1982"
TL;DR: Biochemical-pharmacological studies on the prepared compounds aided in establishing that the alpha- carboxyl grouping of the glutamate moiety contributes to the binding of MTX to dihydrofolate reductase while the gamma-carboxyl does not.
Abstract: N-[4-[[(Benzyloxy)carbonyl]methylamino]benzoyl]-L-glutamic acid alpha-benzyl ester (2) and gamma-benzyl ester (6) served as key intermediates in syntheses of precursors to amides and peptides of methotrexate (MTX) involving both the alpha- and gamma-carboxyl groupings of the glutamate moiety. Coupling of 2 and 6 at the open carboxyl grouping with amino compounds was affected by the mixed anhydride method (using isobutyl chloroformate); carboxyl groupings of amino acids coupled with 2 and 6 were protected as benzyl esters. N-[4-[[(Benzyloxy)carbonyl]methylamino]benzoyl]-L-glutamic acid gamma-methyl ester (5), a precursor to MTX gamma-methyl ester, was prepared from L-glutamic acid gamma-methyl ester and 4-[[(benzyloxy)carbonyl]methylamino]benzoyl chloride (1) in a manner similar to that used to prepare 2 and 6. The precursor to MTX alpha-methyl ester was prepared from gamma-benzyl ester 6 by treatment with MeI in DMF containing (i-Pr)2NEt. Benzyl and (benzyloxy)carbonyl protective groupings were removed by hydrogenolysis, and the deprotected side-chain precursors were converted to alpha- and gamma-substituted amides, peptides, and esters of MTX by alkylation with 6-(bromomethyl)-2,4-pteridinediamine hydrobromide (12). Biochemical-pharmacological studies on the prepared compounds aided in establishing that the alpha-carboxyl grouping of the glutamate moiety contributes to the binding of MTX to dihydrofolate reductase while the gamma-carboxyl does not. Other studies on the peptide MTX-gamma-Glu (13h) are concerned with the contribution toward antifolate activity of this metabolite of MTX. The compounds prepared were also evaluated and compared with MTX with respect to cytotoxicity toward H.Ep.-2 cells and effect on L1210 murine leukemia.
68 citations
TL;DR: The major alkaloid of a Fijian Melodinus sp. (family Apocynaceae) has been identified as (+)-scandine (1) as mentioned in this paper.
Abstract: The major alkaloid of a Fijian Melodinus sp. (family Apocynaceae) has been identified as (+)-scandine (1). The crystal structure and absolute configuration of the acetone solvate of (+)-scandine hydrobromide have been determined by X-ray diffraction; diffractometer data at 295 K were refined by block diagonal least squares to a residual of 0.037 (2657 'observed' reflections). Crystals of the hydrobromide are monoclinic, P21, a 9.496(3), b 14.561(5), c 9.339(3) A, β 115.39(2)o, Z 2. Although the cations of (+)-scandine hydrobromide and (+)-N-methylmeloscine bromide have the same skeleton and the same absolute configuration, they have different conformations; this appears to be due to the steric effect of the N-methyl group in the latter cation.
23 citations
TL;DR: (+/-)-2-Depentylperhydrohistrionicotoxin, several of its analogues, and N- and O-substituted derivatives were prepared and tested for their effects on the neuromuscular transmission of the frog sartorius muscle.
Abstract: (+/-)-2-Depentylperhydrohistrionicotoxin (4), several of its analogues, and N- and O-substituted derivatives were prepared and tested for their effects on the neuromuscular transmission of the frog sartorius muscle. Compound 4, its N-methyl derivative 5, the O-acetyl derivative 9, and the quaternary methiodides 19 and 20 blocked the indirectly elicited twitch. The oxidation of 4 and 5 to ketones 12 and 14 and their reduction to the epimeric alcohols 17 and 18 afforded materials with substantially reduced activity. N-Acetylation of 4 to 11 changed the course of the activity to a transient potentiation of muscle twitch. Both 4 and 5 were not very toxic to mice after subcutaneous administration. (+/-)-7-n-Butyl-1-azaspiro[5,5]undecan-8-one (12) epimerized readily at room temperature to afford the epimer 13, and preparation of the hydrochloride of its N-methylated derivative 14 was accompanied by a retro-Michael reaction, affording the 2-n-butyl-3-[4-(methylamino)butyl]cyclohexene-2-one (22). The strongly hydrogen-bonded alcohol 4 was analyzed as the hydrobromide by a single-crystal X-ray analysis, confirming its structure.
20 citations
TL;DR: A single subcutaneous dose of 100 mgkg−1 BRL 6231 completely cleared and eliminated an established infection of P. berghei N strain in mice, whereas similar infections in mice dosed at 100 mg kg−1 of cycloguanil or chloroquine recrudesced several days after initial clearance.
Abstract: From a large series of chlorophenoxyalkoxy N-substituted triazines with antimalarial activity against Plasmodium berghei infections in mice, the 2,4,5-trichloropropyloxy-1,3,5-triazine hydrobromide (BRL 51084) and hydrochloride (BRL 6231) were selected. These two compounds were almost equally effective against both the drug-sensitive N strain and the cycloguanil- resistant B line. In four-day suppressive tests against the N strain, BRL 6231 had an ED90 of 0·34 mg kg−1 and against the B line an ED90 of 0·89 mg kg−1 when given subcutaneously for four days. A pyrimethamine-resistant line of P. berghei was found to be fully sensitive to BRL 6231 by the same dose route.A single subcutaneous dose of 100 mg kg−1 BRL 6231 completely cleared and eliminated an established infection of P. berghei N strain in mice, whereas similar infections in mice dosed at 100 mg kg−1 of cycloguanil or chloroquine recrudesced several days after initial clearance.Causal prophylaxis studies in mice showed that a single subcutaneous d...
19 citations
TL;DR: In this paper, the electric birefringence and circular dichroism spectra of poly( l -ornithine hydrobromide) have been measured in ethanol/water, 2-propanol/water and tertiary butyl alcohol/water mixtures of various compositions.
9 citations
TL;DR: In this article, the crystal structure of koumine hydrobromide (C20H22N2O HBr) was solved by Patterson and Fourier methods and refined to an R value of 0.067 by full-matrix least-square method.
Abstract: The crystal structure of alkaloide, koumine Hydrobromide (C20H22N2O HBr), has been solved by Patterson and Fourier methods and refined to an R value of 0.067 by full-matrix least-square method. The crystal belongs to orthorhombic system with the unit cell parameters: a = 14.307 A, b = 12.053 A, c = 9.862 A; and four molecules are contained in the cell. The space group is P212121. The positions of all hydrogen acoms have been found from a difference Fourier map calculated after the refinement of co-ordinates of all non-hydrogen atoms with anisotropic thermal parameters by least-squares method. The absolute configuration of the molecule has been established. The structural characteristics of the molecule were discussed.
8 citations
TL;DR: The title compounds exist in pH-dependent equilibrium between cation and ring-opened anion; since pK 2 1, the hypothetical neutral species is always metastable as discussed by the authors.
6 citations
TL;DR: In this paper, a 2-Bromo-[1-14C]ethanamine hydrobromide (BEA) was synthesized from [2- 14C]ETHan-1-01-2-amine hydrochloride, by reaction with HBr in a specially designed chamber at an elevated temperature.
Abstract: 2-Bromo-[1-14C]ethanamine hydrobromide (BEA) was synthesized from [2-14C]ethan-1-01-2-amine hydrochloride, by reaction with HBr in a specially designed chamber at an elevated temperature. The synthetic product was purified in the reaction chamber by fractional vacuum sublimation to give a yield of up to 90% of BEA having a purity greater than 95%.
3 citations
Patent•
12 Jul 1982
TL;DR: In this paper, the 1-benzoylmethylimidazole compound of formula I or formula II (R is H or lower alkyl; X is halogen; X' is H/ halogen).
Abstract: NEW MATERIAL:The 1-benzoylhalomethylimidazole compound of formula I or formula II (R is H or lower alkyl; X is halogen; X' is H or halogen). EXAMPLE: 1-Benzoylmonobromomethylimidazole hydrobromide. USE: Mildewcide, antimycotic agent, insect attractant, etc. PROCESS: The compound of formula I can be prepared by reacting the imidazole compound of formula III with halogenated acetophenone in a solvent such as dimethylformamide at 5W80°C, and reacting the resultant 1-benzoylmethylimidazole compound with a mixture of a halogen and acetic acid. COPYRIGHT: (C)1984,JPO&Japio
2 citations
1 Jan 1982
1 citations