- PYRIDINYL SULFONAMIDE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
The invention relates to new pyridinyl sulfonamide derivatives of the formula (I) wherein R1, A and n are as defined in the description and claims, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.
- -
-
Page/Page column 54; 71
(2020/05/29)
-
- Design, synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor
-
Twenty eight new aryloxybenzene analogues were synthesized and their in vitro binding potencies toward S1PR2 were determined using a [32P]S1P competitive binding assay. Out of these new analogues, three compounds, 28c (IC50 = 29.9 ± 3.9 nM), 28e (IC50 = 14.6 ± 1.5 nM), and 28g (IC50 = 38.5 ± 6.3 nM) exhibited high binding potency toward S1PR2 and high selectivity over the other four receptor subtypes (S1PR1, 3, 4, and 5; IC50 > 1000 nM). Each of the three potent compounds 28c, 28e, and 28g contains a fluorine atom that will allow to develop F-18 labeled PET radiotracers for imaging S1PR2.
- Luo, Zonghua,Liu, Hui,Klein, Robyn S.,Tu, Zhude
-
p. 3619 - 3631
(2019/07/05)
-
- Remote C(sp3)-H Oxygenation of Protonated Aliphatic Amines with Potassium Persulfate
-
This letter describes the development of a method for selective remote C(sp3)-H oxygenation of protonated aliphatic amines using aqueous potassium persulfate. Protonation serves to deactivate the proximal C(sp3)-H bonds of the amine substrates and also renders the amines soluble in the aqueous medium. These reactions proceed under relatively mild conditions (within 2 h at 80 °C with amine as limiting reagent) and do not require a transition metal catalyst. This method is applicable to a variety of types of C(sp3)-H bonds, including 3°, 2°, and benzylic C-H sites in primary, secondary, and tertiary amine substrates.
- Lee, Melissa,Sanford, Melanie S.
-
supporting information
p. 572 - 575
(2017/02/10)
-
- FUSED RING HETEROARYL COMPOUNDS AND THEIR USE AS TRK INHIBITORS
-
The disclosure provides novel chemical compounds represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof. The compounds can be used as an inhibitor of Trk and are useful in the treatment of pain, cancer, inflammation, neurodegenerative disease and certain infectious diseases. In some compounds of Formula I, Q is —CH═CR3C(O)NR4R5, —C≡CC(O)NR4R5, or
- -
-
-
- Synthesis and biological evaluation of picolinamides as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
-
Synthesis of a series of 6-substituted picolinamide derivatives and their inhibitory activities against 11β-hydroxysteroid dehydrogenase type 1 are described. Optimization of the initial hit compound, N-cyclohexyl-6-(piperidin-1-yl)picolinamide (1) from high throughput screening of in-house library resulted in the discovery of the highly potent and metabolically stable compound 25, which was efficacious in a mouse ex vivo pharmacodynamic model and reduced the fasting blood glucose and insulin levels in a HF/STZ mouse model after oral dosing.
- Ryu, Je Ho,Kim, Shinae,Han, Hye Young,Son, Hyun Joo,Lee, Hyun Jung,Shin, Young Ah,Kim, Jae-Sun,Park, Hyeung-Geun
-
p. 695 - 700
(2015/01/30)
-
- TYK2 INHIBITORS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
- -
-
-
- IMIDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING PHARMACOKINETICS OF DRUG
-
Imidazole derivatives of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising at least one imidazole derivative are disclosed. The imidazole derivatives are effective to inhibit CYP450 3A and can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.
- -
-
-
- IMIDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG
-
The present invention relates to Imidazole Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Y, R1 and R2 are as defined herein. The present invention also relates to compositions comprising at least one Imidazole Derivative, and and methods of using the Imidazole Derivatives for inhibiting CYP450 3A. Inhibition of CYP450 3A can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.
- -
-
-
- HEPATITIS B ANTIVIRAL AGENTS
-
The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.
- -
-
-
- KINASE INHIBITORS
-
Compounds of formula (I) or a pharmaceutically acceptable salt thereof: formula (I) wherein R2, W, A, Y and R1 are as defined in the specification, are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
- -
-
-
- NOVEL HETEROCYCLYL COMPOUNDS
-
The invention is concerned with novel heterocyclyl compounds of formula (I): wherein A, X, R3, R4, R5, R6, R7, R8, R9, R10, m, n and p are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are antagonists of CCR2 receptor, CCR5 receptor and/or CCR3 receptor and may be used as medicaments.
- -
-
Page/Page column 23
(2010/02/17)
-
- AZAARENE DERIVATIVES
-
A compound represented by the general formula: wherein X1 represents a nitrogen atom or a group represented by the formula -CR10=; X2 represents a nitrogen atom or a group represented by the formula -CR11=; Y represents an oxygen atom or the like; R1 represents a C1-6 alkoxy group, an optionally substituted C6-10 aryloxy group, a group represented by the formula -NR12aR12b or the like; R2 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like; R3, R4, R5, R6, R7, R8, R10 and R11 each independently represent a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, or the like; R9 represents a group represented by the formula -NR16aR16b or the like; and R12a, R12b, R16a and R16b each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, a salt thereof, or a hydrate of the foregoing.
- -
-
Page/Page column 53
(2008/06/13)
-
- Pyrazole compounds, pharmaceutical compositions, and methods for modulating or inhibiting ERAB or HADH2 activity
-
Pyrazole compounds represented by the formula: are described. The pyrazole compounds and pharmaceutical compositions containing them may be used in inhibiting ERAB or HADH2 activity and in treating ERAB, HADH2 or amyloid-β mediated diseases and conditions
- -
-
-
- Regioselective oxyfunctionalization of unactivated tertiary and secondary C-H bonds of alkylamines by methyl(trifluoromethyl)dioxirane in acid medium
-
Tetrafluoroborate salts of primary, secondary, and tertiary alkylamines are resistant toward N oxidation by methyl(trifluoromethyl)dioxirane (1b), which allows the selective oxidation of aliphatic tertiary and secondary C-H bonds in the alkyl side chain. The oxidations are carried out at 0°C with a ketone-free solution of methyl(trifluoromethyl)-dioxirane (1b) in methylene chloride. By this procedure, within 3 h the tertiary C-H bonds of acyclic, cyclic, and polycyclic amines 2a-e are hydroxylated to give the corresponding amino alcohols 3a-e. In the case of the acyclic amines 2a,b longer reaction times were necessary, and in the strong acid medium the corresponding amino acetamides 4a,b were obtained through Ritter reaction with the solvent acetonitrile. The strong electron-withdrawing nature of the ammonium group deactivates the oxidation of even tertiary C-H bonds at the α and β positions. Secondary C-H bonds of the linear aliphatic primary amines 2f-h were oxidized exclusively at the ∈ position to give the 2,3,4,5-tetrahydro-6-alkylpyridines 6f-h after intramolecular condensation of the corresponding amino ketones 5f-h.
- Asensio, Gregorio,González-Nú?ez, María Elena,Bernardini, Carmen Boix,Mello, Rossella,Adam, Waldemar
-
p. 7250 - 7253
(2007/10/02)
-