127446-34-8Relevant academic research and scientific papers
NEW ANTIBACTERIAL COMPOUNDS
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, (2018/01/19)
The present invention relates to novel antibacterial compounds, pharmaceutical compositions containing them and their use as antimicrobials.
Synthesis of a cis 2,5-disubstituted morpholine by de-epimerization: Application to the multigram scale synthesis of a mineralocorticoid antagonist
Sammons, Matthew,Jennings, Sandra M.,Herr, Michael,Hulford, Catherine A.,Wei, Liuqing,Hallissey, James F.,Kiser, E. Jason,Wright, Stephen W.,Piotrowski, David W.
, p. 934 - 939 (2013/07/26)
A convergent route to multigram quantities of a mineralocorticoid antagonist 3 is described. Starting from (R)-phenylglycinol, the synthesis of cis 2,5-morpholine 2 is accomplished utilizing a de-epimerization to install the second stereogenic center. The multigram synthesis of 3 was completed through a sequence of an SNAr reaction, Dakin oxidation, alkylation, and cyclization to provide a crystalline solid.
FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS
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, (2012/01/15)
The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.
The synthesis of a dopamine D2 partial agonist for the treatment of schizophrenia
Magano, Javier,Acciacca, Alison,Akin, Anne,Collman, Benjamin M.,Conway, Brian,Waldo, Michael,Chen, Michael H.,Mennen, Kenneth E.
experimental part, p. 555 - 566 (2010/04/22)
The synthesis of the phosphoric acid salt of dopamine D2 partial agonist 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]- butoxy}-5,6,7,9-tetrahydro- 1,7,9-triaza-benzocyclohepten-8- one (1) is reported. The most prominent feature of the molecule is a seven-membered ring urea functionality that has been prepared via an efficient one-pot, three-step transformation. The original synthesis from the Medicinal Chemistry group provided precursor 13 in 10 steps and 2% overall yield, required four chromatographies and employed unsafe reagents such as 2-iodoxybenzoic acid (IBX) and HClO4. The optimized synthetic route for the preparation of phosphate salt 1 consists of 12 linear steps with a 10% overall yield. Safer and more robust reaction conditions have been developed with only one required chromatography. Another key step in the synthesis is the coupling of iodide 25 with naphthalenopiperazine 12 to provide 13. Due to the difficulty to purify this intermediate, a protocol had to be developed to obtain crude material with the required purity, suitable for use in the subsequent salt formation step. Finally, considerable work was carried out to determine the most stable polymorph of the API. As a result, a robust set of conditions has been developed for the formation of phosphoric acid salt 1, providing the desired polymorph in excellent yield and purity.
Synthesis and structure-activity relationships of 7-substituted 3-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as selective inhibitors of pp60(c-src)
Thompson,Rewcastle,Boushelle,Hartl,Kraker,Lu,Batley,Panek,Hollis Showalter,Denny
, p. 3134 - 3147 (2007/10/03)
7-Substituted 3-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-ones are potent inhibitors of protein tyrosine kinases, with some selectivity for c-Src. The compounds were prepared by condensing 4,6-diaminonicotinaldehyde with 2,6-dichlorophenylacetonitrile and selectively converting the 2- and 7-amino groups of the product to hydroxy and fluoro groups, respectively, by prolonged diazotization in 50% aqueous fluoboric acid. N-Methylation, followed by treatment with aliphatic diamines, aromatic amines, or their derived lithium anions, gave the desired compounds. Selected isomeric 1,8-naphthyridin-2(1H)-ones were also prepared in order to evaluate the relative contributions of both ring A aza atoms of the related pyrido[2,3-d]pyrimidin-7(8H)-ones to the inhibitory activity. The compounds were evaluated for their ability to prevent phosphorylation of a model substrate by c-Src, FGF-1 receptor, and PDGF-β receptor enzymes. Overall, there was a high degree of correlation of the activities against the different kinases, with c-Src being generally the most sensitive to structural changes. 1,6-Naphthyridin-2(1H)-one analogues bearing basic aliphatic side chains [7-NH(CH2)(n)NRR, 7-NHPhO(CH2)(n)NRR, or 7-NHPhN(CH2)4NMe] were the most potent against c-Src (IC50s of 10-80 nM), showing good selectivity with respect to PDGFR (10-300-fold) but less with respect to FGFR. The 1,6-naphthyridin-2(1H)-ones showed broadly similar activity to the analogous pyrido[2,3-d]-pyrimidin-7(8H)-ones, whereas the 1,8-naphthyridin-2(1H)-ones were at least 103-fold less potent. These results, indicating that the 3-aza atom in the pyrido[2,3-d]pyrimidin-7(8H)-ones is mandatory, whereas the 1-aza atom is not, support the published binding model for these compounds to c-Src (J. Med. Chem. 1998, 41, 1752), where the 3-aza and 2-NH atoms form a bidentate H-bond donor - acceptor motif that interacts with Met341 and the 1-aza atom is not involved in specific binding interactions.
A General Approach to the Synthesis of 1,6-, 1,7-, and 1,8-Naphthyridines
Turner, James A.
, p. 4744 - 4750 (2007/10/02)
A new three-step procedure for pyridine annulation is described and illustrated with efficient syntheses of various 1,6-, 1,7-, and 1,8-naphthyridin-2-ones as well as 6-chloroquinolin-2-one.The regiospecific ortho metalation and subsequent formylation of
