106447-97-6Relevant articles and documents
Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms
Webber, R. Keith,Metz, Suzanne,Moore, William M.,Connor, Jane R.,Currie, Mark G.,Fok, Kam F.,Hagen, Timothy J.,Hansen Jr., Donald W.,Jerome, Gina M.,Manning, Pamela T.,Pitzele, Barnett S.,Toth, Mihaly V.,Trivedi, Mahima,Zupec, Mark E.,Siong Tjoeng
, p. 96 - 101 (1998)
A series of analogues of 2-iminopiperidine have been prepared and shown to be potent inhibitors of the human nitric oxide synthase (NOS) isoforms. Methyl substitutions on the 4-position (3) or 4- and 6-positions (8) afforded the most potent analogues. These compounds exhibited IC50 values of 0.1 and 0.08 μM, respectively, for hiNOS inhibition. Substitution with cyclohexylmethyl at the 6-position (13) afforded an inhibitor that showed the best selectivity for hiNOS versus heNOS (heNOS IC50/hiNOS IC50 = 64). Following oral administration, inhibitors were found to decrease serum nitrite/nitrate levels in an in vivo rat endotoxin assay. This series of 2- iminopiperidines were prepared via the described synthetic methodologies. The effect of ring substitutions on potency and selectivity for this class of cyclic amidines as NOS inhibitors is described.
Preparation method of 2-amino substituted six-membered nitrogen-containing heterocycle complex
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Paragraph 0025; 0026; 0095, (2019/02/08)
The invention discloses a preparation method of a 2-amino substituted six-membered nitrogen-containing heterocycle complex. The preparation method comprises the following steps: mix 2-fluorine substituted six-membered nitrogen-containing heterocycle complex and amidine hydrochloride salt compound, and then react under the action of a alkaline substance to obtain a 2-amino substituted six-memberednitrogen-containing heterocycle complex. Preferably, the 2-amino substituted six-membered nitrogen-containing heterocycle complex is a 2-amino pyridine compound, a 2-aminopyrimidine compound or a 2-aminopyrazine compound. Compared with the prior art, the method has the advantages of simple synthesis conditions, less reaction steps, mild reaction conditions, low cost of the catalyst used, less waste discharge and good functional group tolerance.
METHOD OF INHIBITING HAMARTOMA TUMOR CELLS
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Page/Page column 20, (2012/08/28)
Dimorpholinopyrimidines are useful for inhibiting growth or proliferation of hamartoma tumor cells. Because the Dimorpholinopyrimidines inhibit the growth and proliferation of hamartoma tumor cells they are also useful in treating PTEN hamartoma tumor syndromes. The therapeutic and prophylactic treatments provided by this invention are practiced by administering to a patient in need thereof an amount of a compound of dimorpholinopyrimidine derivative that is effective to inhibit growth or proliferation of the hamartoma tumor cells.
Identification of NVP-BKM120 as a potent, selective, orally bioavailable class i PI3 kinase inhibitor for treating cancer
Burger, Matthew T.,Pecchi, Sabina,Wagman, Allan,Ni, Zhi-Jie,Knapp, Mark,Hendrickson, Thomas,Atallah, Gordana,Pfister, Keith,Zhang, Yanchen,Bartulis, Sarah,Frazier, Kelly,Ng, Simon,Smith, Aaron,Verhagen, Joelle,Haznedar, Joshua,Huh, Kay,Iwanowicz, Ed,Xin, Xiaohua,Menezes, Daniel,Merritt, Hanne,Lee, Isabelle,Wiesmann, Marion,Kaufman, Susan,Crawford, Kenneth,Chin, Michael,Bussiere, Dirksen,Shoemaker, Kevin,Zaror, Isabel,Maira, Sauveur-Michel,Voliva, Charles F.
supporting information; experimental part, p. 774 - 779 (2011/12/03)
Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.