53135-24-3Relevant articles and documents
Amide compounds and uses thereof
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Page/Page column 145, (2021/10/11)
Provided herein are novel amide compounds of formula (I), pharmaceutical compositions comprising same, methods for preparing same, and uses thereof, wherein the definition of each symbol is as described in the description.
Structure-based design of a new series of N-(piperidin-3-yl)pyrimidine-5-carboxamides as renin inhibitors
Imaeda, Yasuhiro,Tawada, Michiko,Suzuki, Shinkichi,Tomimoto, Masaki,Kondo, Mitsuyo,Tarui, Naoki,Sanada, Tsukasa,Kanagawa, Ray,Snell, Gyorgy,Behnke, Craig A.,Kubo, Keiji,Kuroita, Takanobu
, p. 5771 - 5780 (2016/10/30)
The action of the aspartyl protease renin is the rate-limiting initial step of the renin-angiotensin-aldosterone system. Therefore, renin is a particularly promising target for blood pressure as well as onset and progression of cardiovascular and renal diseases. New pyrimidine derivatives 5–14 were designed in an attempt to enhance the renin inhibitory activity of compound 3 identified by our previous fragment-based drug design approach. Introduction of a basic amine essential for interaction with the two aspartic acids in the catalytic site and optimization of the S1/S3 binding elements including an induced-fit structural change of Leu114 (‘Leu-in’ to ‘Leu-out’) by a rational structure-based drug design approach led to the discovery of N-(piperidin-3-yl)pyrimidine-5-carboxamide 14, a 65,000-fold more potent renin inhibitor than compound 3. Surprisingly, this remarkable enhancement in the inhibitory activity of compound 14 has been achieved by the overall addition of only seven heavy atoms to compound 3. Compound 14 demonstrated excellent selectivity over other aspartyl proteases and moderate oral bioavailability in rats.
CYCLIC AMINOMETHYL PYRIMIDINE DERIVATIVE
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Paragraph 0293-0295, (2016/06/01)
The present invention provides a cyclic aminomethyl pyrimidine derivative and a pharmaceutically acceptable salt thereof with high selectivity for dopamine D4 receptors, which are useful for treating a disease such as attention deficit hyperactivity disorder. Specifically, a compound of formula (1) or a pharmaceutically acceptable salt thereof is provided, wherein n and m are independently 1 or 2; Ra is C1-6 alkyl group, C3-6 cycloalkyl group, or amino group; Rb is hydrogen atom, C1-6 alkyl group or the like, provided that when Ra is amino group, then Rb is hydrogen atom; Rc1 and Rc2 are independently hydrogen atom, or C1-6 alkyl group; Rd1 and Rd2 are independently hydrogen atom, fluorine atom or the like; ring Q is an optionally-substituted pyridyl group or an optionally-substituted isoquinolyl group; and the bond having a dashed line is a single or double bond.
