《Pyridopyrimidinone derivatives as potent and selective c-Jun N-terminal kinase (JNK) inhibitors》 was written by Zheng, Ke; Park, Chul Min; Iqbal, Sarah; Hernandez, Pamela; Park, HaJeung; LoGrasso, Philip V.; Feng, Yangbo. Computed Properties of C6H7N3O2S And the article was included in ACS Medicinal Chemistry Letters on April 9 ,2015. The article conveys some information:
A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure-activity relationships (SARs) were systematically developed utilizing biochem. and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. (trans)-1-Isopropyl-3-[4-(8-isopropyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-yl-amino)-cyclohexyl]urea (I), was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 μM), had high potency in functional cell based assays, and had high stability in human liver microsome (t1/2 = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of (I) and (trans)-1-[4-(8-Cyclopentyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-cyclohexyl]-3-isopropyl-urea in JNK3 were solved at 2.0 Å. These structures elucidated the binding mode (Type-I binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition. The results came from multiple reactions, including the reaction of 4-Amino-2-(methylthio)pyrimidine-5-carboxylic acid(cas: 771-81-3Computed Properties of C6H7N3O2S)
4-Amino-2-(methylthio)pyrimidine-5-carboxylic acid(cas: 771-81-3) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).Computed Properties of C6H7N3O2S
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia