RESUMEN
The practical use of the average and difference intensities of Friedel opposites at different stages of structure analysis has been investigated. It is shown how these values may be properly and practically used at the stage of space-group determination. At the stage of least-squares refinement, it is shown that increasing the weight of the difference intensities does not improve their fit to the model. The correct form of the coefficients for a difference electron-density calculation is given. In the process of structure validation, it is further shown that plots of the observed and model difference intensities provide an objective method to evaluate the fit of the data to the model and to reveal insufficiencies in the intensity measurements. As a further tool for the validation of structure determinations, the use of the Patterson functions of the average and difference intensities has been investigated and their clear advantage demonstrated.
RESUMEN
X-Ray crystallography unequivocally determined the stereochemistry of the thymine base in the title compound, C(14)H(18)N(2)O(7). The absolute stereochemistry was determined from the use of d-ribose as the starting material. There are two independent mol-ecules in the asymmetric unit (Z' = 2) which exist as N-Hâ¯O hydrogen-bonded pairs in the crystal structure.
RESUMEN
X-ray crystallography unequivocally confirmed the stereochemistry of the 2-C-methyl group in the title mol-ecule, C(10)H(16)O(6), in which the 1,5-lactone ring exists in a boat conformation. The use of d-galactose in the synthesis determined the absolute stereochemistry. The crystal exists as O-Hâ¯O hydrogen-bonded layers in the ab plane, with each mol-ecule acting as a donor and acceptor for two hydrogen bonds.
RESUMEN
The crystal structure of the title compound, C(12)H(18)N(2)O(8), exists as O-Hâ¯O hydrogen-bonded layers of mol-ecules running parallel to the ab plane. Each mol-ecule is a donor and acceptor for six hydrogen bonds. The absolute stereochemistry was determined by the use of d-glucuronolactone as the starting material.
RESUMEN
The title compound, [Pt(C(4)H(10)O(3)PS)(C(15)H(10)ClN(3))](C(24)H(20)B), has a distorted square-planar coordination geometry at the platinum(II) centre, due to the constraints of the tridentate terpyridine ligand. The Pt(II)-bound diethylphosphinothioate ligand takes up a conformation to avoid non-bonding contacts with atoms H6 and H6".
RESUMEN
Lucidene has been shown to be derived from alpha-humulene and o-benzoquinone methide generated under thermal conditions.
Asunto(s)
Benzoquinonas/síntesis química , Sesquiterpenos/síntesis química , Benzoquinonas/química , Cristalografía por Rayos X , Imitación Molecular , Sesquiterpenos Monocíclicos , Plantas/química , Sesquiterpenos/químicaRESUMEN
A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta-homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi-homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha-homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha-glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta-mannosidases but were moderately good as inhibitors of rice and some mammalian alpha-glucosidases. Compound 4 was active in the micromolar range toward all alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than 1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds 5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution structure of 1 has been determined by X-ray diffraction and showed a chair conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin) predominantly equatorial to the piperidine ring in the crystal structure. This preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR coupling constants. The coupling constants for 7 suggest the axial orientation of the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH axial conformation appears to be responsible for more potent inhibition toward processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive against HIV-1 replication at 500 microg/mL as measured by inhibition of virus-induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl-1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was 37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha-glucosidase I than 1 and 8 both in vitro and in the cell culture system. These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores de Glicósido Hidrolasas , Piperidinas/química , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/síntesis química , 1-Desoxinojirimicina/química , 1-Desoxinojirimicina/farmacología , Animales , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Bovinos , Línea Celular Transformada , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Iminopiranosas , Espectroscopía de Resonancia Magnética , Conformación Molecular , Estructura Molecular , Piperidinas/farmacología , Ratas , Estereoisomerismo , Relación Estructura-Actividad , Células Tumorales Cultivadas , Replicación Viral/efectos de los fármacosRESUMEN
The crystal and molecular structures of ten compounds with strong structural resemblances to the cimetidine group of histamine H2-receptor antagonists, but exhibiting selective H1-receptor antagonist activity, (1)-(7), or H1 and H2 activity (8)-(10), have been determined: (1) 2-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-5- (6-methyl-3-pyridylmethyl)-4-pyrimidone trihydrobromide (temalastine), C21H27BrN5O3+.3Br-, M(r) = 685.09, triclinic, P1, a = 6.314 (2), b = 11.192 (2), c = 19.441 (5) A, alpha = 102.47 (2), beta = 92.77 (2), gamma = 103.28 (2) degrees, V = 1298.51 A3, Z = 2, Dx = 1.75 g cm-3, mu = 61.6 cm-1, F(000) = 672, R = 2.93% for 3208 independent reflexions. (2) 2-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4-pyrimidone, C14H19BrN4O2, M(r) = 355.23, monoclinic, I2/a, a = 16.359 (3), b = 10.469 (6), c = 18.339 (4) A, beta = 90.90 (2) degrees, V = 3140.49 A3, Z = 8, Dx = 1.503 g cm-3, mu = 26.0 cm-1, F(000) = 1176, R = 4.2% for 1872 independent reflexions. (3) 3-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4- amino-1,2,5-thiadiazole-1-oxide, C12H16BrN5OS, M(r) = 358.26, triclinic, P1, a = 14.295 (2), b = 12.447 (2), c = 9.917 (2) A, alpha = 95.77 (2), beta = 113.86 (2), gamma = 106.91 (1) degrees, V = 1495.18 A3, Z = 4, Dx = 1.59 g cm-3, mu = 50.96 cm-1, F(000) = 728, R = 5.98% for 5674 independent reflexions. (4) 3-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4- benzylamino-1,2,5-thiadiazole-1-oxide, C19H22BrN5OS, M(r) = 448.38, monoclinic, P2(1)/c, a = 36.293 (7), b = 4.826 (2), c = 11.528 (3) A, beta = 96.91 (2) degrees, V = 2004.27 A3, Z = 4, Dx = 1.49 g cm-3, mu = 39.2 cm-1, F(000) = 920, R = 12.1% for 1945 independent reflexions. (5) 2-[3-(N-Benzyl-N-2- pyridylamino)propylamino]-4-pyrimidone, C19H21N5O, M(r) = 335.4, orthorhombic, Pbna, a = 7.082 (1), b = 19.889 (3), c = 24.899 (3) A, V = 3507.16 A3, Z = 8, Dx = 1.27 g cm-3, mu = 6.24 cm-1, F(000) = 1424, R = 4.05% from 2470 independent reflexions. (6) 3-[3-(N-4-Fluorobenzyl-N-2- pyridylamino)propylamino]-4-ethylamino-1,2,5-thiadiazole-1-oxide, C19H23FN6OS, M(r) = 402.5, monoclinic, P2(1)/n, a = 6.686 (2), b = 14.717 (3), c = 20.850 (5) A, beta = 97.83 (2) degrees, V = 2032.47 A3, Z = 4, Dx = 1.32 g cm-3, mu = 16.41 cm-1, F(000) = 848, R = 8.5% from 2484 independent reflexions. (7) 5-(6-Methyl-3-pyridylmethyl)-2-[3-(5,6,7,8-tetrahydro-8- quinolyl)propylamino]-4-pyrimidone, C23H29N5O2, M(r) = 407.5, monoclinic, P2(1)/c, a = 14.966 (2), b = 16.075 (2), c = 9.1608 (9) A, beta = 99.158 (8) degrees, V = 2175.83 A3, Z = 4, Dx = 1.24 g cm-3, mu = 6.19 cm-1; F(000) = 872, R = 5.3% from 2784 independent reflexions. (8) 2-(4-Phenylbutylamino)-5-(3-pyridyl-methyl)-4-pyrimidone, C20H26N4O3, M(r) = 370.5, monoclinic, P2(1)/c, a = 8.040 (4), b = 21.279 (4), c = 11.404 (2) A, beta = 92.08 (5) degrees, V = 1949.68 A3, Z = 4, Dx = 1.26 g cm-3, mu = 0.93 cm-1, F(000) = 792, R = 4.05% from 3816 independent reflexions.(ABSTRACT TRUNCATED AT 400 WORDS)