1632-59-3Relevant academic research and scientific papers
2, 4-diaminopyrimidine compound containing phenol fragment, preparation method, pharmaceutical compositions and use thereof
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Paragraph 0131; 0134; 0135, (2018/04/02)
The invention discloses a 2, 4-diaminopyrimidine compound containing phenol fragment with a general formula I shown in the specification, pharmaceutically acceptable salts or pharmaceutically acceptable solvates, a preparation method thereof, pharmaceutical compositions containing the compounds, and use of the compounds in preparation of drugs for preventing or treating anaplastic lymphoma kinaserelated abnormal cell proliferation, morphological changes, hyperkinesia and other associated diseases in organisms, and angiogenesis or cancerometastasis associated diseases, especially use in drugsfor treating or preventing tumor growth and metastasis.
Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists
Asano, Masayoshi,Nakamura, Tsuyoshi,Sekiguchi, Yukiko,Mizuno, Yumiko,Yamaguchi, Takahiro,Tamaki, Kazuhiko,Shimozato, Takaichi,Doi-Komuro, Hiromi,Kagari, Takashi,Tomisato, Wataru,Inoue, Ryotaku,Yuita, Hiroshi,Oguchi-Oshima, Keiko,Kaneko, Reina,Nara, Futoshi,Kawase, Yumi,Masubuchi, Noriko,Nakayama, Shintaro,Koga, Tetsufumi,Namba, Eiko,Nasu, Hatsumi,Nishi, Takahide
scheme or table, p. 3083 - 3088 (2012/06/04)
We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P3-sparing S1P1 agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P1, and over 5800-fold selectivity against S1P3. In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria.
Method of treating bone disease with pyridine, carboxamide and carboxylic derivatives
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, (2008/06/13)
Treatment of osteopathic comprising administering as an active ingredient a compound represented by the following formula (I), (II) or (III): STR1
Heteroacetic acid derivatives
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, (2008/06/13)
Disclosed are compounds of formula STR1 wherein R is hydroxy, esterified hydroxy or etherified hydroxy; R1 is halogen, trifluoromethyl or lower alkyl; R2 is halogen, trifluoromethyl or lower alkyl; R3 is halogen, trifluoromethyl, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; or R3 is the radical STR2 wherein R8 is hydrogen, lower alkyl, aryl, cycloalkyl, aryl-lower alkyl or cycloalkyl-lower alkyl; R9 is hydroxy or acyloxy; R10 represents hydrogen or lower alkyl; or R9 and R10 together represent oxo; R4 is hydrogen, halogen, trifluoromethyl or lower alkyl; X is --NR7, S or O; W is O or S; R5 represents hydrogen, lower alkyl or aryl-lower alkyl;and R6 represents hydrogen; or R5 and R6 together represent oxo provided that X represents --NR7; R7 represents hydrogen or lower alkyl; Z represents carboxyl, carboxyl derivatized as a pharmaceutically acceptable ester or as a pharmaceutically acceptable amide; and pharmaceutically acceptable salts thereof; which are useful as hypocholesteremic agents.
Synthesis and Structure-Activity Relationships among α-Adrenergic Receptor Agonists of the Phenylethanolamine Type
Leclerc, Gerard,Bizec, Jean Claude,Bieth, Nicole,Schwartz, Jean
, p. 738 - 744 (2007/10/02)
Nineteen arylethanolamine derivatives related to norepinephrine were prepared and tested for α-adrenergic stimulant activity.In one series the analogues possess a p-hydroxy function, while the meta position is substituted by methyl, ethyl, isopropyl, cyclohexyl, fluoro, chloro, iodo, carboxy, carbomethoxy, and methylsulfamido groups.The other series is meta hydroxylated with the para position substituted by the same groups.The influence of these groups upon the α-adrenergic activity is discussed, and the compounds are compared to octopamine, normetanephrine,norepinephrine, and norphenylephrine.It has been found that the introduction of an isopropyl, cyclohexyl, and fluoro group in the meta position of octopamine improves its affinity by three, five, and six times, respectively, whereas when these groups are introduced in the para position of norphenylephrine their effects are always detrimental.The most active compound, α-(aminomethyl)-(4-fluoro-3-hydroxyphenyl)methanol (44), has about one-hundreth the affinity and the same intrinsic activity as norepinephrine.
