Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe.
Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe.
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新型和选择性骨形态发生蛋白受体（BMP）抑制剂的合成和结构活性关系从吡唑洛斯[1.5-A]吡胺胺的嘧啶支架衍生而来：ML347的发现ML347作为ALK2对ALK2对ALK3对ALK3的选择性MLPCN探针。
DOI：
10.1016/j.bmcl.2013.03.113
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发表时间：
2013-06-01
影响因子：
2.7
通讯作者：
Hopkins, Corey R.
中科院分区：
文献类型：
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作者：
Engers, Darren W.;Frist, Audrey Y.;Lindsley, Craig W.;Hong, Charles C.;Hopkins, Corey R.
已知BMP抑制剂dorsomorphin， 1, LDN193189, 2和DMH1, 3的pyrazolo[1,5- A]嘧啶支架的3位和6位的结构-活性关系，导致鉴定出ALK2对抗ALK3的有效和选择性化合物。几个3位取代基的效价贡献是通过细微的结构变化来评估的，这导致了效价的显著变化。通过这些研究，我们发现了一个新的5-喹啉分子，并将其命名为MLPCN探针分子ML347，该分子对ALK2的选择性为50 - 300倍，为进一步的生物学评价提供了一个有选择性的分子探针。
A structure-activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency. From these studies, a novel 5-quinoline molecule was identified and designated an MLPCN probe molecule, ML347, which shows >300-fold selectivity for ALK2 and presents the community with a selective molecular probe for further biological evaluation.
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影响因子：
1.8
作者：
Daniels, R. Nathan;Kim, Kwangho;Lindsley, Craig W.
通讯作者：
Lindsley, Craig W.
影响因子：
6.1
作者：
Shi, SongTing;Hoogaars, Willem M. H.;'t Hoen, Peter A. C.
通讯作者：
't Hoen, Peter A. C.
影响因子：
30.8
作者：
Shore, EM;Xu, MQ;Kaplan, FS
通讯作者：
Kaplan, FS
影响因子：
14.8
作者：
Yui, Paul B.;Hong, Charles C.;Peterson, Randall T.
通讯作者：
Peterson, Randall T.
影响因子：
82.9
作者：
通讯作者：
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