Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist.

Kassack MU; Braun K; Ganso M; Ullmann H; Nickel P; Boing B; Muller G; Lambrecht G

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Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist.

机译：NF449类似物的构效关系证实了NF449是最有效和选择性最强的P2X1受体拮抗剂。

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NF449 [4,4',4",4"'-(carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino)))tet rakisbenzene-1,3-disulfonic acid-octasodiumsalt)] was recently described to inhibit recombinant rP2X(1) receptors (Naunyn Schmiedeberg's Arch. Pharmacol. 364 (2001) 285). The purpose of this study was to examine structure-activity-relationships at P2 receptors of a series of NF449 analogues. Thus, compounds containing various arylaminemono-, di-, or trisulfonic acids and a replacement of the central urea bridge were synthesized. NF449 displayed a pIC(50) at P2X(1) receptors (rat vas deferens) of 6.31 +/- 0.04 being at least 19-fold more potent at P2X(1) than at P2X(3), P2Y(1), P2Y(2), or P2Y(11). Any deletion or change of position of sulfonic acid groups or replacing the central urea bond by the bisamide of terephthalic acid reduced the potency at P2X(1) by at least 90%. All compounds were very weak antagonists at P2Y(2) or P2Y(11) receptors (pIC(50) < 4.5). In conclusion, NF449 remains the most potent and selective P2X(1)antagonist known. Potential lead compounds among the suramin class for P2X(3) (16d) and P2Y(1) (16a) receptors were identified.

机译：最近描述了NF449 [4,4'，4“，4”'-（羰基双（亚氨基-5,1,3-苯三基-双（羰基亚氨基））tet rakis苯-1,3-二磺酸-八钠盐）]抑制重组rP2X（1）受体（Naunyn Schmiedeberg's Arch。Pharmacol。364（2001）285）。这项研究的目的是检查一系列NF449类似物的P2受体的结构-活性-关系。因此，合成了包含各种芳基胺单，二或三磺酸和中心脲桥的取代基的化合物。 NF449在P2X（1）受体（大鼠输精管）上显示pIC（50）为6.31 +/- 0.04，在P2X（1）上的效力至少是P2X（3），P2Y（1），P2Y的19倍（2）或P2Y（11）。磺酸基团的位置的任何缺失或改变，或由对苯二甲酸的双酰胺取代中心脲键，都会使P2X（1）的效能至少降低90％。所有化合物都是P2Y（2）或P2Y（11）受体的非常弱的拮抗剂（pIC（50）<4.5）。总之，NF449仍然是已知的最有效和最具选择性的P2X（1）拮抗剂。确定了苏拉明类中P2X（3）（16d）和P2Y（1）（16a）受体的潜在铅化合物。

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《European Journal of Medicinal Chemistry: Chimie Therapeutique》 |2004年第4期|共13页
作者
Kassack MU; Braun K; Ganso M; Ullmann H; Nickel P; Boing B; Muller G; Lambrecht G;
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正文语种 eng
中图分类基础医学;
关键词
NF449; receptor; Urea; Acids; 尿素; 酸类;

机译：NF449;receptor;Urea;Acids;尿素;酸类;

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1. Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist. [J] . Kassack MU, Braun K, Ganso M, European Journal of Medicinal Chemistry: Chimie Therapeutique . 2004,第4期

机译：NF449类似物的构效关系证实了NF449是最有效和选择性最强的P2X1受体拮抗剂。
2. Structure-activity relationships of pyridoxal phosphate derivatives as potent and selective antagonists of P2X1 receptors. [J] . Kim YC, Brown SG, Harden TK, Journal of Medicinal Chemistry . 2001,第3期

机译：吡ido醛磷酸衍生物作为P2X1受体的有效和选择性拮抗剂的结构活性关系。
3. Synthesis and structure-activity relationships of 4-amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide derivatives, novel and potent serotonin 5-HT3 and dopamine D2 receptors dual antagonist. [J] . Hirokawa Y, Harada H, Yoshikawa T, Chemical and Pharmaceutical Bulletin . 2002,第7期

机译：4-氨基-5-氯-N-（1,4-二烷基六氢-1,4-二氮杂-6-6基）-2-甲氧基苯甲酰胺衍生物，新型和有效的5-羟色胺5-HT3和多巴胺D2的合成及构效关系受体双重拮抗剂。
4. Structure-activity relationship studies of new cyclic MSH analogues using cloned-human melanocortin receptors lead to greater selectivity and inverse agonists [C] . Minying Cai, Paolo Grieco, Jonathan Wiens, the International Peptide Symposium . 2001

机译：使用克隆人黑素激素受体的新循环MSH类似物的结构 - 活性关系研究导致更大的选择性和反向激动剂
5. Synthesis of new glutamate receptor probes: I. Total synthesis of dysiherbaine, a potent glutamate receptor excitotoxin; II. Design and synthesis of dysiherbaine analogues; III. Synthesis and structure-activity relationships of substituted benzothiadiazides and their role as AMPA receptor modulators. [D] . Phillips, Dean Paul. 2001

机译：新型谷氨酸受体探针的合成：I. dysiherbaine的全合成，一种有效的谷氨酸受体兴奋性毒素；二。 dysiherbaine类似物的设计和合成；三，取代的苯并噻二叠氮化物的合成及其构效关系及其作为AMPA受体调节剂的作用。
6. Molecular basis of selective antagonism of the P2X1 receptor for ATP by NF449 and suramin: contribution of basic amino acids in the cysteine-rich loop [O] . S El-Ajouz, D Ray, RC Allsopp, 2012

机译：NF449和苏拉明对ATP的P2X1受体选择性拮抗的分子基础：富含半胱氨酸环中碱性氨基酸的贡献
7. Molecular basis of selective antagonism of the P2X1 receptor for ATP by NF449 and suramin: contribution of basic amino acids in the cysteine-rich loop. [O] . El-Ajouz, S, Ray, D, Allsopp, RC, 2012

机译：NF449和苏拉明对ATP的P2X1受体选择性拮抗的分子基础：富含半胱氨酸环中碱性氨基酸的贡献。

Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist.

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