排序方式: 共有23条查询结果,搜索用时 343 毫秒
1.
Hong Q Bakshi RK Palucki BL Park MK Ye Z He S Pollard PG Sebhat IK Liu J Guo L Cashen DE Martin WJ Weinberg DH MacNeil T Tang R Tamvakopoulos C Peng Q Miller RR Stearns RA Chen HY Chen AS Strack AM Fong TM MacIntyre DE Wyvratt MJ Nargund RP 《Bioorganic & medicinal chemistry letters》2011,21(8):2330-2334
We report the discovery of piperazine urea based compound 1, a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models. 相似文献
2.
MARIÁN PERNÝ VLADISLAV KOLARIK L'UBO MAJESKÝ PAVOL MÁRTONFI 《Botanical journal of the Linnean Society. Linnean Society of London》2008,157(3):475-485
Cytogeographical variability within the Phleum pratense group in the Carpathians and adjacent part of Pannonian lowland, based on 132 populations analysed by flow cytometry, is described. Only diploid and hexaploid plants were detected among 635 samples from the studied area. Diploids were found to be less frequent (127 plants, 20%) than hexaploids (508, 80%). With the exception of the single pure diploid population, diploids always co-occured with hexaploids (30 localities, 22.7%). The majority of populations (101, 76.5%) consisted of hexaploid plants. Most mixed populations occur in the Western Carpathians (26). In the Eastern Carpathians, mixed populations are much rarer, with three populations in Ukraine and one in Romania. In the Southern Carpathians, only hexaploids occur. The conventional taxonomic concept of the two species, diploid P. bertolonii and hexaploid P. pratense , was followed in spite of their sympatric occurence. Distribution maps based on chromosome number data from previous studies and on ploidy level estimates are given for both species in the studied area. The pattern of different distribution of the two taxa within the Carpathians is discussed. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society , 2008, 157 , 475–485. 相似文献
3.
Graham TH Liu W Verras A Sebhat IK Xiong Y Bleasby K Bhatt UR Chen Q Garcia-Calvo M Geissler WM Gorski JN He H Lassman ME Lisnock J Li X Shen Z Tong X Tung EC Wiltsie J Xiao J Xie D Xu S Hale JJ Pinto S Shen DM 《Bioorganic & medicinal chemistry letters》2012,22(8):2811-2817
A new structural class of potent prolylcarboxypeptidase (PrCP) inhibitors was discovered by high-throughput screening. The series possesses a tractable SAR profile with sub-nanomolar in vitro IC(50) values. Compared to prior inhibitors, the new series demonstrated minimal activity shifts in pure plasma and complete ex vivo plasma target engagement in mouse plasma at the 20 h post-dose time point (po). In addition, the in vivo level of CNS and non-CNS drug exposure was measured. 相似文献
4.
He S Ye Z Dobbelaar PH Bakshi RK Hong Q Dellureficio JP Sebhat IK Guo L Liu J Jian T Lai Y Franklin CL Reibarkh M Holmes MA Weinberg DH MacNeil T Tang R Tamvakopoulos C Peng Q Miller RR Stearns RA Chen HY Chen AS Strack AM Fong TM Wyvratt MJ Nargund RP 《Bioorganic & medicinal chemistry letters》2010,20(22):6524-6532
We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models. 相似文献
5.
Sinem DEMRBA-SARIKAYA Hatice AKIR Devrim G
ZÜAIK Yunus AKKO 《Turkish Journal of Biology》2021,45(3):235
Autophagy and DNA repair are two essential biological mechanisms that maintain cellular homeostasis. Impairment of these mechanisms was associated with several pathologies such as premature aging, neurodegenerative diseases, and cancer. Intrinsic or extrinsic stress stimuli (e.g., reactive oxygen species or ionizing radiation) cause DNA damage. As a biological stress response, autophagy is activated following insults that threaten DNA integrity. Hence, in collaboration with DNA damage repair and response mechanisms, autophagy contributes to the maintenance of genomic stability and integrity. Yet, connections and interactions between these two systems are not fully understood. In this review article, current status of the associations and crosstalk between autophagy and DNA repair systems is documented and discussed. 相似文献
6.
Sebhat IK Lai Y Barakat K Ye Z Tang R Kalyani RN Vongs A Macneil T Weinberg DH Cabello MA Maroto M Teran A Fong TM Van der Ploeg LH Patchett AA Nargund RP 《Bioorganic & medicinal chemistry letters》2007,17(20):5720-5723
SAR about the piperidine core in a series of MC4R agonists is described. A number of alkyl substituents that furnish compounds with good affinity and functional potency are reported. 相似文献
7.
Genya Mitani Masato Sato Jeong IK Lee Nagatoshi Kaneshiro Miya Ishihara Naoshi Ota Mami Kokubo Hideaki Sakai Tetsutaro Kikuchi Joji Mochida 《BMC biotechnology》2009,9(1):17-11
Background
Although the clinical results of autologous chondrocyte implantation for articular cartilage defects have recently improved as a result of advanced techniques based on tissue engineering procedures, problems with cell handling and scaffold imperfections remain to be solved. A new cell-sheet technique has been developed, and is potentially able to overcome these obstacles. Chondrocyte sheets applicable to cartilage regeneration can be prepared with this cell-sheet technique using temperature-responsive culture dishes. However, for clinical application, it is necessary to evaluate the characteristics of the cells in these sheets and to identify their similarities to naive cartilage. 相似文献8.
MARTIN REICHARD MATEJ POLAČIK 《Biological journal of the Linnean Society. Linnean Society of London》2010,100(1):62-72
Allopatric populations separated by vicariance events are expected to evolve reproductive isolating mechanisms as a result of disparate selection pressures and genetic drift. The appearance of reproductive isolating mechanisms may vary across taxa with differences in the opportunity for mate choice, and may be asymmetrical. In addition, premating barriers may be affected by individual mating experience. We used choice and no‐choice experiments to investigate reproductive isolation between two allopatric (island and mainland) and colour‐differentiated populations of an African annual fish, Nothobranchius korthausae. Assortative mating under experimental conditions was limited and asymmetrical. Preference for sympatric males was only expressed in nonvirgin females from one population. Virgin fish from both populations mated indiscriminately. No difference in the number of eggs laid, fertilization rate and hatching success was detected in no‐choice experiments. All mating combinations produced viable offspring and no postmating barriers were detected in terms of the performance and fertility of F1 hybrids. Overall, we found little evidence for significant reproductive isolation, which is in contrast with the related killifish taxa in which assortative mating can be strong, even among allopatric populations with no colour differentiation. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100 , 62–72. 相似文献
9.
Jian Liu Shuwen He Tianying Jian Peter H. Dobbelaar Iyassu K. Sebhat Linus S. Lin Allan Goodman Cheng Guo Peter R. Guzzo Mark Hadden Alan J. Henderson Kevin Pattamana Megan Ruenz Bruce J Sargent Brian Swenson Larry Yet Constantin Tamvakopoulos Qianping Peng Jie Pan Yanqing Kan Ravi P. Nargund 《Bioorganic & medicinal chemistry letters》2010,20(7):2074-2077
This Letter describes a series of potent and selective BRS-3 agonists containing a biarylethylimidazole pharmacophore. Extensive SAR studies were carried out with different aryl substitutions. This work led to the identification of a compound 2-{2-[4-(pyridin-2-yl)phenyl]ethyl}-5-(2,2-dimethylbutyl)-1H-imidazole 9 with excellent binding affinity (IC50 = 18 nM, hBRS-3) and functional agonist activity (EC50 = 47 nM, 99% activation). After oral administration, compound 9 had sufficient exposure in diet induced obese mice to demonstrate efficacy in lowering food intake and body weight via BRS-3 activation. 相似文献
10.
Shuwen He Zhixiong Ye Peter H. Dobbelaar Iyassu K. Sebhat Liangqin Guo Jian Liu Tianying Jian Yingjie Lai Christopher L. Franklin Raman K. Bakshi James P. Dellureficio Qingmei Hong David H. Weinberg Tanya MacNeil Rui Tang Alison M. Strack Constantin Tamvakopoulos Qianping Peng Randy R. Miller Ralph A. Stearns Ravi P. Nargund 《Bioorganic & medicinal chemistry letters》2010,20(15):4399-4405
We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models. 相似文献