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101.
5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase. 相似文献
102.
Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno
−, m−, p− isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain
mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed
for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data
of ring-substituted compounds. The best correlated QSAR equations are as follows: pI50=0.804 Π2 Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI50=1.815 π-0.825 Π2 R+0.900 Es2+0.869 Es3+0.796 Es4−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference
between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of
MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group,
a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position,
and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries,
hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site
near ortho position constitute active sites of MAO-B. 相似文献
103.
Changes of Intestinal Caicitonin Gene-related Peptide in Acute Intestinal Radiation Sickness in Rats
The characteristic distribution of calcitonin gone-related peptide(CGRP)inthe small intestine of rats and its changes in acute intestinal radiation sickness(AIRS)were studied with immunocytochemistry(whole mount stretch preparations of the smallintestine and cryostat sections)and radio-immunoassay.It was found that in all the lay-ers of the intestinal walls,there were large amounts of CGRP immunoreactive(CGRP-I)nerve fibers which existed in especiaUy high density in the myenteric,submucosal andmucosal plexuses.There was also a rather high density of the nerves around the smallvessels of the small intestine and the intestinal crypts.Some CGRP-I neurons were seenin the myenteric and submucosal plexuses.In AIRS,the intestinal CGRP showed a dip-hasic change,in a lower level in the 24th h and a higher level in the 48th and 72nd h af-ter irradiation.The results indicate that CGRP may be related to the regulation of the motility,se-cretion,absorption,sensation,and regional blood flow of the gastrointestinal tract.Pro-bably,CGRP is released under the stress of AIRS and participates in the mechanism ofinjury through many ways especially through the influence on the regional blood flowand the increase of the permeability of blood vessels. 相似文献
104.
Daniel W. Walsh Vincent B. Ho Michael F. Haggerty 《Journal of magnetic resonance imaging : JMRI》1997,7(2):312-315
Mycotic aneurysms of the abdominal aorta are potentially fatal but uncommon. We report the MRI and MRA features of an abdominal aortic mycotic aneurysm in a patient who presented with nonspecific low back pain. By delineating the saccular nature of the aneurysm and identifying the coexistence of vertebral enhancement, MRI was crucial for the final diagnosis. A potential pitfall of contrast-enhanced MRA is also demonstrated. 相似文献
105.
106.
Intensive chemotherapy for peripheral T-cell lymphomas. 总被引:3,自引:0,他引:3
Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy. 相似文献
107.
108.
109.
T M Ko C Y Hsieh H N Ho F J Hsieh T Y Lee 《American journal of obstetrics and gynecology》1991,164(3):901-906
To determine the genetic origin of the complete hydatidiform mole, 20 abnormal pregnancies were studied with restriction fragment length polymorphism with five genomic probes: EJ 6.6, beta-globin gene, 3'alpha-hypervariable region, J-Bir, and St14. In the 12 cases of molar pregnancy, pure paternal origin was proved in 11 cases, but both maternal and paternal inheritance were shown in only one case. In the cases with pure paternal origin, all of the restriction fragment length polymorphisms were homozygous, although those of the fathers were heterozygous at 15 loci. In the four cases that mimicked hydatidiform mole but were diagnosed as hydropic change of villi, both paternal and maternal inheritance were noted. In the four pregnancies with blighted ovum, both paternal and maternal inheritance were shown in three cases; and in one case with a balanced translocation between chromosomes 13 and 14, only paternal inheritance was noted. This study showed that most of the complete hydatidiform moles were caused by fertilization of an empty egg by a duplicated haploid sperm, but rare exceptions may exist. 相似文献
110.