共查询到20条相似文献,搜索用时 31 毫秒
1.
Georgsson J Rosenström U Wallinder C Beaudry H Plouffe B Lindeberg G Botros M Nyberg F Karlén A Gallo-Payet N Hallberg A 《Bioorganic & medicinal chemistry》2006,14(17):5963-5972
Two pentapeptides, Ac-Tyr-Ile-His-Pro-Phe/Ile, were synthesized and shown to have angiotensin II AT2 receptor affinity and agonistic activity. Based on these peptides, a new series of 13 pseudopeptides was synthesized via introduction of five different turn scaffolds replacing the Tyr-Ile amino acid residues. Pharmacological evaluation disclosed subnanomolar affinities for some of these compounds at the AT2 receptor. Substitution of Phe by Ile in this series of ligands enhanced the AT2 receptor affinity of all compounds. These results suggest that the C-terminal amino acid residues can be elaborated on to enhance the AT2 receptor affinity in truncated Ang II analogues. 相似文献
2.
Strappaghetti G Corsano S Barbaro R Giannaccini G Betti L 《Bioorganic & medicinal chemistry》2001,9(3):575-583
A series of 8-substituted xanthines were synthesized and their affinity in vitro towards A1, A2A-adenosine receptors was evaluated by radioligand receptor binding assays. All compounds showed a greater affinity and selectivity towards the A1-adenosine receptor than theophylline. The compounds in which the n-proyl group is in 1-position of the xanthine nucleus and the pyridazinone system in 8-position is linked through a chain of two or four carbon atoms, showed the highest affinity and selectivity. 相似文献
3.
Ji Q Gao J Wang J Yang C Hui X Yan X Wu X Xie Y Wang MW 《Bioorganic & medicinal chemistry letters》2005,15(11):2891-2893
A series of estrogen receptor ligands based on benzothieno[3,2-b]indole were synthesized and their binding affinity for estrogen receptor subtypes (ERalpha and ERbeta) and effects on mouse uterus and bone were evaluated. Some of these compounds showed strong binding affinity to ER and significantly increased the bone mineral density of ovariectomized mice. 相似文献
4.
Lee-Dutra A Arienti KL Buzard DJ Hack MD Khatuya H Desai PJ Nguyen S Thurmond RL Karlsson L Edwards JP Breitenbucher JG 《Bioorganic & medicinal chemistry letters》2006,16(23):6043-6048
A series of 2-arylbenzimidazoles was synthesized and found to bind with high affinity to the human histamine H(4) receptor. Structure-activity relationships were investigated through library preparation and evaluation as well as traditional medicinal chemistry approaches, leading to the discovery of compounds with single-digit nanomolar affinity for the H(4) receptor. 相似文献
5.
Stavitskaya L Shim J Healy JR Matsumoto RR MacKerell AD Coop A 《Bioorganic & medicinal chemistry》2012,20(14):4556-4563
A series of phenylpropyloxyethylamines and cinnamyloxyethylamines were synthesized as deconstructed analogs of 14-phenylpropyloxymetopon and analyzed for opioid receptor binding affinity. Using the Conformationally Sampled Pharmacophore modeling approach, we discovered a series of compounds lacking a tyrosine mimetic, historically considered essential for μ opioid binding. Based on the binding studies, we have identified the optimal analogs to be N-methyl-N-phenylpropyl-2-(3-phenylpropoxy)ethanamine, with 1520 nM, and 2-(cinnamyloxy)-N-methyl-N-phenethylethanamine with 1680 nM affinity for the μ opioid receptor. These partial opioid structure analogs will serve as the novel lead compounds for future optimization studies. 相似文献
6.
Fang J Akwabi-Ameyaw A Britton JE Katamreddy SR Navas F Miller AB Williams SP Gray DW Orband-Miller LA Shearin J Heyer D 《Bioorganic & medicinal chemistry letters》2008,18(18):5075-5077
A series of estrogen receptor ligands based on a 3-alkyl naphthalene scaffold was synthesized using an intramolecular enolate-alkyne cycloaromatization as the key step. Several of these compounds bearing a C6-OH group were shown to be high affinity ligands. All compounds had similar ERalpha and ERbeta binding affinity ranging from micromolar to low nanomolar. 相似文献
7.
Huffman JW Bushell SM Joshi SN Wiley JL Martin BR 《Bioorganic & medicinal chemistry》2006,14(1):247-262
Two new series of cannabinoids were prepared and their affinities for the CB1 and CB2 receptors were determined. These series are the (2'R)- and (2'S)-1-methoxy- and 1-deoxy-3-(2'-methylalkyl)-delta8-tetrahydrocannabinols, with alkyl side chains of three to seven carbon atoms. These compounds were prepared by a route that employed the enantioselective synthesis of the resorcinol precursors to the cannabinoid ring system. All of these compounds have greater affinity for the CB2 receptor than the CB1 receptor and four of them, (2'R)-1-methoxy-3-(2'-methylbutyl)-delta8-THC (JWH-359), (2'S)-1-deoxy-3-(2'-methylbutyl)-delta8-THC (JWH-352), (2'S)-1-deoxy-3-(2'-methylpentyl)-delta8-THC (JWH-255), and (2'R)-1-deoxy-3-(2'-methylpentyl)-delta8-THC (JWH-255), have good affinity (K(i) = 13-47 nM) for the CB2 receptor and little affinity (K(i) = 1493 to >10,000 nM) for the CB1 receptor. In the 1-deoxy-3-(2'-methylalkyl)-delta8-THC series, the 2'S-methyl compounds in general have greater affinity for the CB2 receptor than the corresponding 2'R isomers. 相似文献
8.
Kitbunnadaj R Hoffmann M Fratantoni SA Bongers G Bakker RA Wieland K el Jilali A De Esch IJ Menge WM Timmerman H Leurs R 《Bioorganic & medicinal chemistry》2005,13(23):6309-6323
In this study, we replaced the basic amine function of the known histamine H(3) receptor agonists imbutamine or immepip with non-basic alcohol or hydrocarbon moieties. All compounds in this study show a moderate to high affinity for the cloned human H(3) receptor and, unexpectedly, almost all of them act as potent agonists. Moreover, in the alcohol series, we consistently observed an increased selectivity for the human H(3) receptor over the human H(4) receptor, but none of the compounds in this series possess increased affinity and functional activity compared to their alkylamine congeners. In this new series of compounds VUF5657, 5-(1H-imidazol-4-yl)-pentan-1-ol, is the most potent histamine H(3) receptor agonist (pK(i) = 8.0 and pEC(50) = 8.1) with a 320-fold selectivity at the human H(3) receptor over the human H(4) receptor. 相似文献
9.
The synthesis and the affinity for the 5-HT(7) receptor and other receptors of a novel series of fused-ring tetrahydropyridine derivatives are described. Some of the compounds showed high affinity for the 5-HT(7) receptor. Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles and are potent ligands for the 5-HT(7) receptor, with high selectivity over the 5-HT(2) receptor and other receptors. These compounds should be useful tools for clarifying the biological role of the 5-HT(7) receptor. 相似文献
10.
Miller CP Jirkovsky I Tran BD Harris HA Moran RA Komm BS 《Bioorganic & medicinal chemistry letters》2000,10(2):147-151
A diastereomerically pure series of 7alpha-thioestratrienes was prepared and evaluated for its affinity for both the human estrogen receptor alpha and the more recently discovered estrogen receptor beta. The functional estrogenic activities of the compounds were measured in a MCF-7 ERE-tk-luciferase assay. The activities and selectivities of the compounds were sensitive to the nature of the thioether side chain. 相似文献
11.
van Oeveren A Pio BA Tegley CM Higuchi RI Wu M Jones TK Marschke KB Negro-Vilar A Zhi L 《Bioorganic & medicinal chemistry letters》2007,17(6):1523-1526
A series of alkylamino-2-quinolinone compounds (3) was discovered as androgen receptor modulators based on an early linear tricyclic quinoline pharmacophore (1). The series demonstrated selective high binding affinity to androgen receptor and potent receptor modulating activities in the cotransfection assays. 相似文献
12.
Wrobleski ML Reichard GA Paliwal S Shah S Tsui HC Duffy RA Lachowicz JE Morgan CA Varty GB Shih NY 《Bioorganic & medicinal chemistry letters》2006,16(14):3859-3863
A series of novel cyclobutane derivatives as potent and selective NK1 receptor antagonists is described. Several compounds in this series exhibited high in vitro binding affinity (Ki 相似文献
13.
A series of tetrahydroisoquinoline-N-phenylamide derivatives were designed, synthesized, and tested for their relative binding affinity and antagonistic activity against androgen receptor (AR). Compound 1b (relative binding affinity, RBA = 6.4) and 1h (RBA = 12.6) showed higher binding affinity than flutamide (RBA = 1), a potent AR antagonist. These two compounds also exerted optimal antagonistic activity against AR in reporter assays. The derivatives were also tested for their activities against another nuclear receptor, farnesoid x receptor (FXR), with most compounds acting as weak antagonists, however, compound 1h behaved as a FXR agonist with activity slightly less than that of chenodeoxycholic acid (CDCA), a natural FXR agonist. 相似文献
14.
Cecchetti V Schiaffella F Tabarrini O Fravolini A 《Bioorganic & medicinal chemistry letters》2000,10(5):465-468
A series of compounds having a piperazine moiety variously linked to the benzothiazine nucleus were synthesized and evaluated for their in vitro alpha-adrenoceptor affinity by radioligand receptor binding assays. Some compounds bearing a oxyalkyl-(2-methoxyphenyl)piperazine side chain were good alpha1-adrenoreceptor ligands. 相似文献
15.
Graeme Semple Britt-Marie Andersson Vijay Chhajlani Jennie Georgsson Magnus Johansson Marcel Lindschoten Fritof Pontén Asa Rosenquist Henrik S?rensen Lars Swanson Marianne Swanson 《Bioorganic & medicinal chemistry letters》2002,12(2):197-200
A new series of 3-aryl pyridone based kappa opioid receptor agonists was designed and synthesised, based on an understanding of the classical kappa opioid receptor pharmacophore. The most potent of the new compounds were comparable to U-69,593 in receptor affinity, selectivity and functional agonist effect at the cloned human kappa opioid receptor. 相似文献
16.
Zhu R Frazier CR Linden J Macdonald TL 《Bioorganic & medicinal chemistry letters》2006,16(9):2416-2418
A series of N6-ethyl-2-alkynyl NECA (5'-N-ethylcarboxamidoadenosine) analogs were synthesized and their binding affinity with the four human adenosine receptors was evaluated. One of the compounds ZR1121 shows high affinity with hA3 receptor and its selectivity over hA1 receptor is 1-2 log orders greater than IB-MECA or Cl-IB-MECA, the currently employed selective A3 agonists. 相似文献
17.
Paillet-Loilier M Fabis F Lepailleur A Bureau R Butt-Gueulle S Dauphin F Delarue C Vaudry H Rault S 《Bioorganic & medicinal chemistry letters》2005,15(16):3753-3757
Virtual screening studies have identified a series of phenylpyrroles as novel 5-HT7 receptor ligands. The synthesis and the affinity for the 5-HT7 receptor of these phenylpyrroles are described. Some of these compounds exhibited high affinity for the 5-HT7 receptors. 相似文献
18.
Synthesis and optimization of novel and selective muscarinic M(3) receptor antagonists 总被引:1,自引:0,他引:1
Kumar N Kaur K Aeron S Dharmarajan S Silamkoti AD Mehta A Gupta S Chugh A Gupta JB Salman M Palle VP Cliffe IA 《Bioorganic & medicinal chemistry letters》2007,17(18):5256-5260
A series of constrained piperidine analogues were synthesized as novel muscarinic M(3) receptor antagonists. Evaluation of these compounds in binding assays revealed that they not only have high affinity for the M(3) receptor but also have high selectivity over the M(2) receptor. 相似文献
19.
Wallinder C Botros M Rosenström U Guimond MO Beaudry H Nyberg F Gallo-Payet N Hallberg A Alterman M 《Bioorganic & medicinal chemistry》2008,16(14):6841-6849
In the investigation of the structure-activity relationship of nonpeptide AT(2) receptor agonists, a series of substituted benzamide analogues of the selective nonpeptide AT(2) receptor agonist M024 have been synthesised. In a second series, the biphenyl scaffold was compared to the thienylphenyl scaffold and the impact of the isobutyl substituent and its position on AT(1)/AT(2) receptor selectivity was also investigated. Both series included several compounds with high affinity and selectivity for the AT(2) receptor. Three of the compounds were also proven to function as agonists at the AT(2) receptor, as deduced from a neurite outgrowth assay, conducted in NG108-15 cells. 相似文献
20.
Więcek M Kottke T Ligneau X Schunack W Seifert R Stark H Handzlik J Kieć-Kononowicz K 《Bioorganic & medicinal chemistry》2011,19(9):2850-2858
Previous studies have shown that several imidazole derivatives possess affinity to histamine H(3) and H(4) receptors. Continuing our study on structural requirements responsible for affinity and selectivity for H(3)/H(4) receptor subtypes, two series of 3-(1H-imidazol-4-yl)propyl carbamates were prepared: a series of unsaturated alkyl derivatives (1-9) and a series possessing a cycloalkyl group different distances to the carbamate moiety (10-13). The compounds were tested for their affinities at the human histamine H(3) receptor, stably expressed in CHO-K1 cells. Compounds 1, 2, 5-7, 10-13 were investigated for their affinities at the human histamine H(4) receptor co-expressed with Gα(i2) and Gβ(1)γ(2) subunits in Sf9 cells. To expand the pharmacological profile, compounds were further tested for their H(3) receptor antagonist activity on guinea pig ileum and in vivo after oral administration to mice. All tested compounds exhibited good affinity for the human histamine H(3) receptor with K(i) values in the range from 14 to 194nM. All compounds were active in vivo after peroral administration (p.o.) to Swiss mice, thus demonstrating their ability to cross the blood-brain barrier. The most potent H(3) receptor ligand of these series was compound 5, 3-(1H-imidazol-4-yl)propyl pent-4-enylcarbamate with the highest affinity (K(i)=14nM). Additionally, compound 3 showed remarkable central nervous system (CNS) H(3)R activity, increasing the N(τ)-methylhistamine levels in mice with an ED(50) value of 0.55mg/kg, p.o. evidencing therefore, a twofold increase of inverse agonist/antagonist potency compared to the reference inverse agonist/antagonist thioperamide. In this study, the imidazole propyloxy carbamate moiety was kept constant. The different lipophilic moieties connected to the carbamate functionality in the eastern part of the molecule had a range of influences on the human H(4) receptor affinity (154-1326nM). 相似文献