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1.
Design and synthesis of antagonists of substance P 总被引:2,自引:0,他引:2
K Folkers S Rosell J Y Chu L A Lu P F Tang A Ljungqvist 《Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry》1986,40(4):295-302
Synthesis and bioassay of about 65 analogs of substance P (SP) over five years yielded the antagonist [D-Arg1,D-Trp7,9,Leu11]-SP, which was named Spantide, and which was used by many investigators as a "tool". Spantide served as a reference antagonist for the design of 47 new peptides toward the goal of more potent inhibitors. Designs emphasized analogs with D-Trp7, D-Trp9, D-Trp10, D-pClPhe10, Nle11, Leu11, Ile11 and Met11, etc. Twenty-one/47 antagonists were superior in potency to that of Spantide, the best was [D-Arg1,D-Na1(5), D-Trp7,9,Nle11]-SP which required a 255-fold increase in SP concentration to give 50% of the maximum response at a concentration of 10(-5)M of the antagonist; this potency is ca. 5 times that of Spantide. For certain, but not all pairs of undecapeptides and truncated analogs, the undecapeptides may be significantly more potent than the truncated counterparts. 相似文献
2.
Pye PJ Rossen K Weissman SA Maliakal A Reamer RA Ball R Tsou NN Volante RP Reider PJ 《Chemistry (Weinheim an der Bergstrasse, Germany)》2002,8(6):1372-1376
A novel three-component condensation followed by a crystallization-induced asymmetric transformation is used to build this key substance P inhibitor intermediate in a short synthetic sequence. 相似文献
3.
Kuethe JT Wong A Wu J Davies IW Dormer PG Welch CJ Hillier MC Hughes DL Reider PJ 《The Journal of organic chemistry》2002,67(17):5993-6000
An efficient asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes is described. Three methods were developed for the preparation of the 2,3-disubstituted cyclopentenones and cyclohexenones, which are key achiral building blocks. These intermediates are reduced catalytically with (R)-2-methyloxazaborolidine in high yield (82-98%) and excellent ee (89-96%). Directed reduction of the chiral allylic alcohols using Red-Al gives exclusively the 1,2-anti stereochemistry (>99:1). Epimerization of the ester center followed by saponification/crystallization affords the desired hydroxyacids in good yield (65-70%) and in high enantiomeric excess (>99%). 相似文献
4.
Based on our structure-activity relationship study of liver X receptor (LXR) ligands, we designed and synthesized fluorescent LXR antagonists containing an unsubstituted or substituted amino group on a phthalimide unit. 相似文献
5.
Design,synthesis and biological activity of rigid cannabinoid CB1 receptor antagonists 总被引:1,自引:0,他引:1
Stoit AR Lange JH Hartog AP Ronken E Tipker K Stuivenberg HH Dijksman JA Wals HC Kruse CG 《Chemical & pharmaceutical bulletin》2002,50(8):1109-1113
The design, synthesis and biological activities of potent pyrazole-based tricyclic CB1 receptor antagonists (2) are described. The key synthetic step involves the ring closure of the lithiated alpha, gamma-keto ester adduct (4). The optimal nitroderivative (28) in this series exhibits a high CB1 receptor affinity (pKi=7.2) as well as very potent antagonistic activity (pA2=8.8) in vitro. The regioselectivity of the pyrazole ring closure is shown to depend strongly on the aromatic substitution pattern of the applied arylhydrazine. 相似文献
6.
Venugopal D. V. R. Karteek Rao Amperayani Uma Devi Parimi Sastry Y. N. Aruna Lakshmi K. Tarak Ramji M. Shiralgi Y. 《Research on Chemical Intermediates》2017,43(10):5755-5778
Research on Chemical Intermediates - Antibiotic-resistant penicillin binding protein (PBPs) production is one of the reasons why bacteria develop resistance to β-lactam antibiotics, and this... 相似文献
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9.
Jin Yi Xu Qian Ran Wei Yi Hua Xiao Ming Wu Qiu Juan Wang Jing Zhang 《中国化学快报》2007,18(3):251-254
A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin Ⅱ AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonism of angiotensin Ⅱ, induced contraction in the rabbit thoracic aortic ring and the results showed that compounds 9a, 9g and 9j exhibited potent antagonistic activity of AT1 receptor. 相似文献
10.
Cluzeau J Oishi S Ohno H Wang Z Evans B Peiper SC Fujii N 《Organic & biomolecular chemistry》2007,5(12):1915-1923
The four diastereomers of 2,5-bis[(3-guanidino)propyl]-1-[3-(4-hydroxyphenyl)propionyl]-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (-) and of 2,5-bis[(3-guanidino)propyl]-1-(4-hydroxyphenylacetyl)-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (-) were synthesized by a divergent methodology from l- and D-glutamic acids. The 11-membered ring core was made by ring closing metathesis of linear bis(allylamines), and the guanidyl functions were introduced by a simultaneous double Mitsunobu reaction using bis(Boc)guanidine. These compounds were designed to mimic cyclic pentapeptide FC131 (c[Gly-D-Tyr-Arg-Arg-Nal]). 相似文献
11.
David M. Andrews Jean-Claude Arnould Pascal Boutron Bénédicte Délouvrie Christian Delvare Kevin M. Foote Annie Hamon Craig S. Harris Christine Lambert-van der Brempt Maryannick Lamorlette Zbegniew M. Matusiak 《Tetrahedron》2009,65(29-30):5805-5816
As part of a structure–activity exploration into LHRH antagonists, structures containing the thieno[2,3-b]pyrrole core were identified as potent antagonists. This letter describes the employment of the Fischer synthesis to access this thienopyrrole and isomeric final compounds. 相似文献
12.
Shi-Chao Xu Shou-Ji Zhu Jing Wang Liang-Wu Bi Yu-Xiang Chen Yan-Ju Lu Yan Gu Zhen-Dong Zhao 《中国化学快报》2017,28(7):1509-1513
p-Menthane type monoterpene derivatives were identified as bio-based compounds with high herbicidal activities. In order to search novel p-menthane type monoterpene derivatives in good performance, a series of novel cis-p-menthane type Schiff base derivatives were designed and synthesized. All target products were easily available novel compounds and characterized by FT-IR, 1H NMR, 13C NMR and ESI+- MS. Their pre-emergence herbicidal activities against annual ryegrass were evaluated. The bioassays indicated that most of the target compounds displayed excellent herbicidal activities in pre-emergence treatment. 相似文献
13.
Medium-ring ketones (8–12 membered ketones) were synthesized based on the intramolecular cyclization of large-ring lactam sulfoxides or sulfones. 相似文献
14.
H. Ali Dondas Samet Belveren Samet Poyraz Ronald Grigg Colin Kilner Marcos Ferrándiz-Saperas Elisabet Selva José M. Sansano 《Tetrahedron》2018,74(1):6-11
Structurally diverse novel 1,4-benzodiazepine analogues related to selective CCKA antagonist MK-329, and CCKB antagonists L-365,260 and YM022 are prepared via palladium-catalyzed three component domino reactions involving allenylation-carbonylation-anion capture in one-pot cascade protocol in good to excellent yields. 相似文献
15.
Tai CL Hung MS Pawar VD Tseng SL Song JS Hsieh WP Chiu HH Wu HC Hsieh MT Kuo CW Hsieh CC Tsao JP Chao YS Shia KS 《Organic & biomolecular chemistry》2008,6(3):447-450
A novel class of (5-(pent-1-enyl)thiophen-2-yl)pyrazole antagonists was discovered, many of which exhibited potent CB1 activity and good CB1/2 selectivity, suggesting that along with a 1,3-transposition of the carbonyl of the pyrazole 3-carboxamide, bioisosteric replacement of the conventional pyrazole 5-aryl group with a thienyl ring substituted with an appropriate alkenyl moiety is viable. 相似文献
16.
Hilary R PlakeThomas B Sundberg Angela R WoodwardStephen F Martin 《Tetrahedron letters》2003,44(8):1571-1574
A series of conformationally constrained and flexible pseudopeptide derivatives of the tripeptide pYVN were prepared as potential antagonists of interactions of phosphotyrosine peptides with the Grb2-SH2 domain. The conformationally constrained compounds contained trans- and cis-cyclopropanes as replacements to enforce locally extended and reverse turn peptide conformations, respectively. 相似文献
17.
J Leban G Rackur I Yamaguchi K Folkers U Bj?rkroth S Rosell N Yanaihara C Yanaihara 《Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry》1979,33(9):664-668
Fourteen analogs of substances P (SP), six previously synthesized by a solution method and eight newly synthesized by a solid-phase technique, have been tested for agonistic and antagonistic activities utilizing the isolated guinea pig ileum. The primary objective is to achieve effective inhibitors of SP. These analogs had agonistic activities ranging from negligible to that equivalent to SP. Six of the fourteen analogs had some degree of antagonistic activity [D-Leu8, D-Phe9]-SP is an analog which constitutes a lead to new substitutions, because it had antagonistic activity, but only negligible agonistic activity. One concept for effective antagonistic activity requires negligible or no agonistic activity. 相似文献
18.
Four α-cyano-containing ethers based on 2-alkoxy-2-naphthylacetonitriles have been designed as a novel structural class of cytochrome P450 fluorescent probes. Their syntheses, fluorescence properties and evaluation in the fluorogenic assay of cytochrome P450 monooxygenase are reported. After P450 enzymatic O-dealkylation, the cyanohydrin metabolite of the four new substrates rearranges to a fluorescent aromatic aldehyde with a larger Stokes shift, and the new substrates exhibit higher specific activities than that of the commercial substrate 7-ethoxyresorufin (ER). 相似文献
19.
Conditions have been developed for an effective synthesis of 7-hydroxy- and 5,7-dihydroxyisoflavones and also of 3-aryloxy-7-hydroxychromones. The disadvantages and advantages of alternative pathways for the synthesis of these compounds are discussed. The proposed method of synthesis permits considerable simplification of the preparation of compounds of these series.T. G. Shevchenko Kiev State University. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 639–643, September–October, 1989. 相似文献
20.
Conditions have been developed for an effective synthesis of 7-hydroxy- and 5,7-dihydroxyisoflavones and also of 3-aryloxy-7-hydroxychromones.
The disadvantages and advantages of alternative pathways for the synthesis of these compounds are discussed. The proposed
method of synthesis permits considerable simplification of the preparation of compounds of these series.
T. G. Shevchenko Kiev State University. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 639–643, September–October,
1989. 相似文献