共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
3.
4.
Incorporation of 3H from delta-(L-alpha-amino (4,5-3H)adipyl)-L-cysteinyl-D-(4,4-3H)valine into isopenicillin N. 总被引:10,自引:4,他引:6
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
1. delta-(L-alpha-Amino[4,5-3H]adipyl)-L-cysteinyl-D-[4,4-3H]valine has been synthesized from its constituent amino acids, the L-alpha-amino[4,5-3H]adipic acid being obtained by reduction with 3H2 of methyl 5-acetamido-5,5-diethoxycarbonylpent-2-enoate and subsequent decarboxylation and hydrolysis. 2. In a cell-free system prepared by lysis of protoplasts of Cephalosporium acremonium 3H was incorporated from the doubly labelled tripeptide into a compound that behaved like penicillin N or isopenicillin N. The relative specific radioactivities of the alpha-aminoadipyl and penicillamine moieties of the penicillin were the same (within experimental error) as those of the alpha-aminoadipic acid and valine residues respectively of the tripeptide. 3. The behaviour of the labelled alpha-aminoadipic acid from the penicillin to the L-amino acid oxidase of Crotalus adamanteus venom showed that it was mainly L-alpha-aminoadipic acid. 4. The results are consistent with the hypothesis that the carbon skeleton of the LLD-tripeptide is incorporated intact into the penicillin molecule and that the first product is isopenicillin N. 相似文献
5.
The influence of lipophilic moieties attached to a 4-1H-imidazole ring on the histamine H3 receptor activity was systematically investigated. Series of 4-(n-alkyl)-1H-imidazoles and 4-(ω-phenylalkyl)-1H-imidazoles were prepared, with an alkyl chain varying from 2–9 methylene groups and from 1–9 methylene groups, respectively. The compounds were tested for their activity on the H3 receptor under in vitro conditions. For the 4-(n-alkyl)-1H-imidazoles the activity is proportional to chain length, ranging from a pA2 value of 6.3±0.2 for 4-(n-propyl)-1H-imidazole to a pA2 value of 7.2±0.1 for 4-(n-decyl)-1H-imidazole. For the series 4-(ω-phenylalkyl)-4H-imidazoles an optimum in H3 activity was found for the pentylene spacer: 4-(ω-phenylpentyl)-1H-imidazole has a pA2 value of 7.8±0.1. 相似文献
6.
Y. Thirupathi Reddy Konjeti R. Sekhar Nidhish Sasi P. Narsimha Reddy Michael L. Freeman Peter A. Crooks 《Bioorganic & medicinal chemistry letters》2010,20(2):600-602
A series of (Z)-5-((N-benzyl-1H-indol-3-yl)methylene)imidazolidine-2,4-dione (9a–9m) and 5-((N-benzyl-1H-indol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (10a–10i) derivatives that incorporate a variety of aromatic substituents in both the indole and N-benzyl moieties have been synthesized. These analogs were evaluated for their radiosensitization activity against the HT-29 cell line. Three analogs, 10a, 10b, and 10c were identified as the most potent radiosensitizing agents. 相似文献
7.
Synthesis of (26,27- 3 H)-25-hydroxycholecalciferol 总被引:5,自引:0,他引:5
8.
Dorota Łażewska Małgorzata Więcek Xavier Ligneau Tim Kottke Lilia Weizel Roland Seifert Walter Schunack Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry letters》2009,19(23):6682-6685
A series of imidazole-containing (non-)chiral carbamates were tested at human histamine H3 receptor (H3R). All compounds displayed Ki values below 100 nM. A trend for a stereoselectivity at human H3R was observed for the chiral α-branched ligands. Selected compounds were also tested at human histamine H4 receptor and showed moderate to weak affinities (118–1460 nM). 相似文献
9.
10.
Mikó T Ligneau X Pertz HH Arrang JM Ganellin CR Schwartz JC Schunack W Stark H 《Bioorganic & medicinal chemistry》2004,12(10):2727-2736
Recent bioisoteric replacements in histamine H3 receptor ligands with an exchange of the imidazole moiety by a piperidino group as well as of the trimethylene chain in 4-((3-phenoxy)propyl)-lH-imidazole derivatives (proxifan class) by an alpha,alpha'-xylendiyl linker represents the starting point in the development of 1-(4-(phenoxymethyl)benzyl)piperidines as a new class of nonimidazole histamine H3 receptor antagonists. According to different strategies in optimization of imidazole-containing antagonists the central benzyl phenyl ether moiety was replaced by numerous other polar functionalities. Additionally, the ortho- and meta-analogues of the lead were synthesized to determine the influence of the position of the piperidinomethyl substituent. The new compounds were tested in an in vitro binding assay for their affinities for cloned human H3 receptors stably expressed in CHO-K1 cells and for their oral in vivo potencies brain in a functional screening assay in the brain of mice. Additionally, activities of selected compounds were determined in the guinea-pig ileum functional test model. In contrast to the analogues ortho-substituted compounds all other compounds maintained respectable affinities for the human H3 receptor (-log Ki values 6.3-7.5). Despite the results from other classes of compounds the 4-methyl substituted derivatives generally displayed higher affinities than the corresponding 4-chloro substituted compounds. In vivo only the inverse phenyl benzyl ether (3) showed worthwhile antagonist potencies. 相似文献
11.
Das S Chatterjee N Bose D Dey SK Munda RN Nandy A Bera S Biswas SK Das Saha K 《Cellular physiology and biochemistry》2012,29(1-2):251-260
Different quinazoline derivatives have showed wide spectrum of pharmacological activities. Some 3-(arylideneamino)-phenylquinazoline-4(3H)-ones have been reported to possess antimicrobial activity. The present study has been undertaken to evaluate the anticancer effect of these quinazolinone derivatives. The quinazolinone derivatives were synthesized as reported earlier. Compounds containing NO(2), OH, OCH(3), or OH and OCH(3) as substituent(s) on the arylideneamino group were named as P(3a), P(3b), P(3c), and P(3d) respectively. Out of these, P(3a) and P(3d) showed better cytotoxic activity than P(3b) and P(3c) on a panel of six cancer cell lines of different origin, namely, B16F10, MiaPaCa-2, HCT116, HeLa, MCF7, and HepG2, though the effect was higher in B16F10, HCT116, and MCF7 cells. P(3a) and P(3d) induced death of B16F10 and HCT116 cells was associated with characteristic apoptotic changes like cell shrinkage, nuclear condensation, DNA fragmentation, and annexin V binding. Also, cell cycle arrest at G1 phase, alteration of caspase-3, caspase-9, Bcl-2 and PARP levels, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in treated B16F10 cells. Treatment with multiple doses of P(3a) significantly increased the survival rate of B16F10 tumor bearing BALB/c mice by suppressing the volume of tumor while decreasing microvascular density and mitotic index of the tumor cells. 相似文献
12.
Haifeng Tang Reynald K. de Jesus Shawn P. Walsh Yuping Zhu Yan Yan Birgit T. Priest Andrew M. Swensen Magdalena Alonso-Galicia John P. Felix Richard M. Brochu Timothy Bailey Brande Thomas-Fowlkes Xiaoyan Zhou Lee-Yuh Pai Caryn Hampton Melba Hernandez Karen Owens Sophie Roy Alexander Pasternak 《Bioorganic & medicinal chemistry letters》2013,23(21):5829-5832
A sub-class of distinct small molecule ROMK inhibitors were developed from the original lead 1. Medicinal chemistry endeavors led to novel ROMK inhibitors with good ROMK functional potency and improved hERG selectivity. Two of the described ROMK inhibitors were characterized for the first in vivo proof-of-concept biology studies, and results from an acute rat diuresis model confirmed the hypothesis that ROMK inhibitors represent new mechanism diuretic and natriuretic agents. 相似文献
13.
Early Events in Maize Seed Development : 1-Methyl-3-phenyl-5-(3-[trifluoromethyl]phenyl)-4-(1H)-Pyridinone Induction of Vivipary 总被引:9,自引:3,他引:6
下载免费PDF全文
![点击此处可从《Plant physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Preharvest sprouting or vivipary is induced in developing maize (Zea mays, inbred Tx 5855 and Va 35) seeds by fluridone, a pyridinone inhibitor of carotenoid biosynthesis. Fluridone has a maximal effect on vivipary at 11 days after pollination (DAP) and little effect at 13 DAP in the inbred maize line Tx 5855. Abscisic acid partially reversed the chemically induced vivipary. Though the precise mechanism of fluridone-induced vivipary is unknown, these results indicate that there are important developmental changes occurring at 11 DAP which reversibly commit the immature embryo to vivipary or dormancy. 相似文献
14.
Jaiprakash N. Sangshetti Rahul R. Nagawade Devanand B. Shinde 《Bioorganic & medicinal chemistry letters》2009,19(13):3564-3567
A novel series of 1,2,3 triazole compounds possessing 1,2,4 oxadiazole ring were efficiently synthesized. Synthesized compounds were evaluated for their in vitro antifungal activities using standard cup plate method. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Compound 11a from the series was more potent than miconazole against Candida albicans (MIC-20) and Aspergillus flavus (MIC-10) whereas equipotent with miconazole against Fusarium oxysporum (MIC-25) and Aspergillus niger (MIC-12.5). Also compound 11h was more potent than miconazole against Candida albicans (MIC-20) and Aspergillus niger (MIC-10) and equipotent with miconazole against Fusarium oxysporum. Compound 11h was equipotent with fluconazole against Aspergillus niger (MIC-10). 相似文献
15.
16.
Jeffrey A. Deskus Douglas D. Dischino Ronald J. Mattson Jonathan L. Ditta Michael F. Parker Derek J. Denhart Dmitry Zuev Hong Huang Richard A. Hartz Vijay T. Ahuja Henry Wong Gail K. Mattson Thaddeus F. Molski James E. Grace Larisa Zueva Julia M. Nielsen Heidi Dulac Yu-Wen Li Mary Guaraldi Michael Azure John E. Macor 《Bioorganic & medicinal chemistry letters》2012,22(21):6651-6655
Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic stability, compound 10 was evaluated for potential development as PET radioligand. Compound [18F]10 was prepared with high radiochemical purity and showed promising binding properties in rat brain imaging experiments. 相似文献
17.
Tadao Asami Nobutaka Takahashi Shigeo Yoshida 《Bioscience, biotechnology, and biochemistry》2013,77(10):2775-2780
A series of 3-(1-alkylaminoalkylidene)-6-methyl-2H-pyran-2,4(3H)-diones was newly synthe-sized, and they were assayed as photosynthetic electron transport (PET) inhibitors because of their structural resemblance to cyanoacrylates and 2-alkylaminoalkylidene-1,3-cyclohexanedione derivatives, which are potent PET inhibitors. Some of the compounds synthesized here showed very high PET inhibition. 相似文献
18.
19.
4-Ethoxy-1-(p-tolyl)-s-triazine-2,6(1H,3H)-dione (TA) promoted mesocotyl growth in dark-grown rice (Oryza sativa L.) seedlings. In cultivars of the japonica type TA alone showed a small promotive effect and TA+gibberellic acid(GA3) had a marked synergistic effect, while in other cultivars, mostly of the indica type, TA alone showed a great promotive effect and TA+GA3 had only an additive effect. In cv. Nato, a typical representative of cultivars showing the second type of response, the concentration of TA giving the greatest growth promotion was around 0.1–0.2 mM. In Nato seedlings treated with TA at 0.1 mM, the mesocotyls continued to elongate for 6 days and reached about 75 mm in length, while the mesocotyls of control seedlings grew to a maximum of about 10 mm and growth was limited to the first 3 days after planting. The TA-induced mesocotyl elongation was mainly the consequence of increased cell multiplication in the meristematic area immediately below the coleoptilar node. GA3, abscisic acid (ABA) and ethylene also stimulated mesocotyl growth in dark-grown Nato seedlings but their effects were much smaller than those of TA. ABA, like GA3, had an additive effect with TA, but ethylene suppressed the effect of TA and resulted in increased lateral expansion in the upper region of the mesocotyls of TA-treated seedlings.Abbreviations ABA
abscisic acid
- GA(s)
gibberellin(s)
- GA3
gibberellic acid
- TA
4-ethoxy-1-(p-tolyl)-s-triazine-2,6(1H,3H)-dione
Part 5 in the series Plant Growth-regulating Activities of Isourea Derivatives and Related Compounds; Part 4=Ogawa et al. (1978) 相似文献
20.
2(I)-O-p-Tolylsulfonylcyclomaltoheptaose was obtained in 42% yield by reaction of 1-(p-tolylsulfonyl)-(1H)-1,2,4-triazole on NaH-deprotonated cyclomaltoheptaose in DMF and further converted into the corresponding mono-2(I),3(I)-manno-epoxide. 相似文献