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1.
Zlatko Janeba Noha Maklad Morris J. Robins 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1729-1743
Copper(I)-catalyzed 5-endo-dig cyclizations of 5-(alkyn-1-yl)uracil derivatives had given poor yields of substituted furo[2, 3]pyrimidin-2-ones unless the uracil ring was substituted at N1 with alkyl or glycosyl groups. This limited flexibility for the synthesis of analogues with varied substituents at N3 and/or C6 of the furo[2, 3]pyrimidin-2-one core has been overcome with 5-(3-hydroxyalkyn-1-yl)uracil compounds with no substituent at N1. Manipulation of the side-chain hydroxyl group gives access to additional furo[2,3-d]pyrimidin-2-one analogues. 相似文献
2.
Abstract A synthesis of imidazo[1, 2-a]pyrazine nucleoside analogues is described. 相似文献
3.
Stefania Barbato Gennaro Piccialli Ciro Santacroce Lorenzo De Napoli Luciano Mayol 《Nucleosides, nucleotides & nucleic acids》2013,32(4):853-866
Abstract The synthesis and the spectral characterization of a number of N4-N4 bridged pyrimidine nucleosides and triazo [4, 3-c] pyrimidine nucleoside analogues are reported. 相似文献
4.
The structure-activity relationship (SAR) of 5-substituted pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione derivatives 5 was investigated for their potential as Chk1 inhibitors for possible chemo- and radio-potentiators in anticancer chemotherapies. In silico virtual screening helped to optimize the substituent on the phenyl ring, and led to identification of the m-carbamoyl group among the 117 analogues tested. Further optimization studies focusing on the docking model of 15 in the active site of Chk1 revealed that 32b (IC(50)=2.8nM) was a more potent inhibitor than UNC-01. 相似文献
5.
《Bioorganic & medicinal chemistry letters》2020,30(21):127474
A novel series of 5H-chromeno[3,4-c]pyridine, 6H-isochromeno[3,4-c]pyridine and 6H-isochromeno[4,3-d]pyrimidine derivatives as dual ROCK1 and ROCK2 inhibitors is described. Optimization led to compounds with sub-nanomolar inhibitory affinity for both kinases and excellent kinome selectivity. Compound 19 exhibited ROCK1 and ROCK2 IC50 of 0.67 nM and 0.18 nM respectively. 相似文献
6.
John M. Fevig Jianxin Feng Karen A. Rossi Keith J. Miller Ginger Wu Chen-Pin Hung Thao Ung Sarah E. Malmstrom Ge Zhang William J. Keim Mary Jane Cullen Kenneth W. Rohrbach Qinling Qu Jinping Gan Mary Ann Pelleymounter Jeffrey A. Robl 《Bioorganic & medicinal chemistry letters》2013,23(1):330-335
A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT2C agonism with excellent selectivity over the closely related 5-HT2A and 5-HT2B receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model. 相似文献
7.
Bowroju Suresh Kuarm Marumamula Hanumaiah Bavanthula Rajitha 《Russian Journal of Bioorganic Chemistry》2021,47(2):593-600
Russian Journal of Bioorganic Chemistry - A series of 11H-xantheno[2,1-c][1,2,5]selenadiazol-11-one derivatives (Va–m) that incorporate a variety of substituents have been synthesized under... 相似文献
8.
Izumi T Sakaguchi J Takeshita M Tawara H Kato K Dose H Tsujino T Watanabe Y Kato H 《Bioorganic & medicinal chemistry》2003,11(12):2541-2550
Structural modification of imiquimod (1), which is known as an interferon-alpha (IFN-alpha) inducer, for the aim of finding a novel and small-molecule tumor necrosis factor-alpha (TNF-alpha) suppressor and structure-activity relationship (SAR) are described. Structural modification of a imiquimod analogue, 4-amino-1-[2-(1-benzyl-4-piperidyl)ethyl-1H-imidazo[4,5-c]quinoline (2), which had moderate TNF-alpha suppressing activity without IFN-alpha inducing activity, led to a finding of 4-chloro-2-phenyl-1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline (10) with potent TNF-alpha suppressing activity. The relation between conformational direction of 2-(4-piperidyl)ethyl group at position 1 and TNF-alpha suppressing activity is also demonstrated by NMR. 相似文献
9.
Abstract Selective glycosylation of 4-amino-5H-imidazo [4, 5-c]-1, 2, 6-thiadiazine 2, 2-dioxide (1) through its 1-benzyl derivative (2) is described. The structures of the compounds are discussed on the basis of 1H nmr 2D homonuclear chemical shift correlations, NOE difference spectroscopy and iterative analyses. 相似文献
10.
Zhu G Conner S Zhou X Shih C Brooks HB Considine E Dempsey JA Ogg C Patel B Schultz RM Spencer CD Teicher B Watkins SA 《Bioorganic & medicinal chemistry letters》2003,13(7):1231-1235
A novel series of pyrrolo[3,4-c] carbazoles fused with a quinolinyl/isoquinolinyl moiety were synthesized and their D1/CDK4 inhibitory and antiproliferative activity were evaluated. Compound 8H, 14H-isoquinolinyl[6,5-a]-pyrrolo[3,4-c]carbazole-7,9-dione (1d) was found to be a highly potent D1/CDK4 inhibitor with an IC(50) of 69 nM. Compound 1d also inhibited tumor cell growth, arrested tumor cells in G1 phase and inhibited pRb phosphorylation. 相似文献
11.
Chien TC Berry DA Drach JC Townsend LB 《Nucleosides, nucleotides & nucleic acids》2005,24(10-12):1971-1996
3-Amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilysilyl-2,3-O-isopropylidene-beta-D-ribofuranosyl)-4-(1,2,4-oxadiazol-3-yl)imidazoles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta-D-ribofuranosyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4,5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1). 相似文献
12.
Tun-Cheng Chien David A. Berry John C. Drach Leroy B. Townsend 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1971-1996
3-Amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl-4-(1,2,4-oxadiazol-3-yl)imidaz-oles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4,5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1). 相似文献
13.
Jiaqiang Cai Mark Baugh Darcey Black Clive Long D. Jonathan Bennett Maureen Dempster Xavier Fradera Jonathan Gillespie Fiona Andrews Sylviane Boucharens John Bruin Kenneth S. Cameron Iain Cumming William Hamilton Philip S. Jones Allard Kaptein Emma Kinghorn Maurice Maidment Iain Martin Ann Mitchell Tommi Meulemans 《Bioorganic & medicinal chemistry letters》2010,20(15):4350-4354
6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile analogues were identified as potent and selective cathepsin S inhibitor against both purified enzyme and in human JY cell based cellular assays. This core has a very stable thio-trapping nitrile war-head in comparison with the well reported pyrimidine-2-carbonitrile cysteine cathepsin inhibitors. Compound 47 is also very potent in in vivo mouse spleenic Lip10 accumulation assays. 相似文献
14.
Griebenow N Buchmueller A Kolkhof P Schamberger J Bischoff H 《Bioorganic & medicinal chemistry letters》2011,21(12):3648-3653
Novel squalene synthase inhibitors are disclosed. The design, synthesis, SAR and pharmacological profile of the compounds are discussed. 相似文献
15.
Manuel Koller David A. Carcache David Orain Peter Ertl Dirk Behnke Sandrine Desrayaud Grit Laue Ivo Vranesic 《Bioorganic & medicinal chemistry letters》2012,22(20):6454-6459
1H-pyrrolo[2,3-c]pyridine-7-carboxamides constitute a new series of allosteric mGluR5 antagonists. Variation of the substituents attached to the heterocyclic scaffold allowed to improve the physico-chemical parameters for optimization of the aqueous solubility while retaining high in vitro potency. 相似文献
16.
Svetlana V. Vasilyeva Anastasya S. Kuznetsova Juliya G. Khalyavina Valeria A. Glazunova Alexander A. Shtil Leonid M. Gornostaev 《Nucleosides, nucleotides & nucleic acids》2013,32(9):615-625
A series of novel fluorescent pyrimidine nucleosides containing 2,1,3-benzoxadiazole or naphtho[1,2,3-cd]indole-6 (2h)-one fragments was designed and synthesized. Introduction of fluorescent fragments into the position 5 of the uridine or cytidine heterocycle was carried out in two ways: by Sonogashira Coupling Reaction and CuI-catalyzed cycloaddition (“click” reaction). The obtained nucleoside derivatives became fluorescent due to the inserted fragments. The excitation wavelength (440–450 nm) was outside the absorption band of many biomolecules and significantly differed from the emission wavelength (560–600 nm). In addition, the intended nucleoside analogs were shown to kill cultured human tumor cells at submicromolar concentrations. 相似文献
17.
David F. Ewing Noureddine Fahmi Grahame Mackenzie Alessandra Pranzo 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):559-563
Abstract A series of d4T analogues have been synthesised in which the 2′,3′-didehydro-2′,3′-dideoxyribose moiety is replaced by a benzo[c]furan core. A simple strategy has been developed to access a range of compounds for biological screening. In addition, a stereoselective approach has been achieved with view to permit more detailed studies. 相似文献
18.
《Steroids》1982,39(6):667-673
The synthesis of [2H8]estradiol, [2H7]estrone, [2H6]2-hydroxyestrone and [2H6]4-hydroxyestrone from estrone (as a source) is described. The high isotopical purity renders the labelled compounds as suitable carriers and internal standards for quantitative gas chromatography — mass spectrometry. The content of protonium-form (i.e. natural) estrogens in the labelled derivatives ranged from 0.12 % to 2.58 %. The perfcrmance of these compounds in quantitative assays using selected ion monitoring has been established; and this allows the determination of estrogens from biological material in the lower picogram range. 相似文献
19.
Sanchez-Martinez C Shih C Faul MM Zhu G Paal M Somoza C Li T Kumrich CA Winneroski LL Xun Z Brooks HB Patel BK Schultz RM DeHahn TB Spencer CD Watkins SA Considine E Dempsey JA Ogg CA Campbell RM Anderson BA Wagner J 《Bioorganic & medicinal chemistry letters》2003,13(21):3835-3839
The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC(50)=45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed. 相似文献
20.
Remon M. Zaki Adel M. Kamal El-Dean Radwan Shaban M. Ammar Mahmoud A. 《Russian Journal of Bioorganic Chemistry》2020,46(1):85-96
Russian Journal of Bioorganic Chemistry - We describe a simple method to synthesize novel 4-cyano-1-morpholin-4-yl-6,7-dihydro-5H-cyclopenta[c]pyridine-3-thione by the reaction of... 相似文献