- CEREBLON BINDERS FOR THE DEGRADATION OF IKAROS
-
The present invention provides cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway along with their use in therapeutic applications as described herein.
- -
-
Page/Page column 311; 312
(2019/10/23)
-
- AZOLE-SUBSTITUTED PYRIDINE COMPOUND
-
The present invention provides a compound represented by formula [I'| shown below or a pharmaceutically acceptable salt thereof that has an inhibitory effect on 20-HETE producing enzyme, wherein the structure represented by formula [III] shown below represents any of the structures represented by formula group [IV] shown below, wherein R1 represents a hydrogen atom, a fluorine atom, methyl, etc.; R2, R3, and R4 each independently represent a hydrogen atom, a fluorine atom, or methyl; W represents a single bond, C1-3alkanediyl, or the formula -O-CH2CH2-; and ring A represents (a) substituted C4-6cycloalkyl, (b) substituted 4- to 6-membered saturated nitrogen-containing heterocyclyl, (c) substituted phenyl, (d) substituted pyridyl, (e) substituted 2,3-dihydrobenzofuran, (f) 4- to 6-membered saturated oxygen-containing heterocyclyl, etc.
- -
-
Paragraph 0647; 0648; 0649
(2019/01/08)
-
- TETRAHYDROISOQUINOLINE DERIVED PRMT5-INHIBITORS
-
A compound of formula I wherein: n is 1 or 2: p is 0 or 1; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl.
- -
-
Page/Page column 121
(2016/03/19)
-
- Antianemic sideropenic sideropenic syndrome and treatment of the complex compound and for prevention of iron (III)
-
The invention relates to iron(III) complex compounds and pharmaceutical compositions comprising them for the use as medicaments, in particular for the treatment and/or prophylaxis of iron deficiency symptoms and iron deficiency anemias.
- -
-
Paragraph 0113
(2016/10/20)
-
- Fe(III) complex compounds for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anemias
-
The invention relates to iron(III) complex compounds and pharmaceutical compositions comprising them for the use as medicaments, in particular for the treatment and/or prophylaxis of iron deficiency symptoms and iron deficiency anemias.
- -
-
Page/Page column 23
(2016/10/17)
-
- Anti-inflammatory agents
-
Disclosed are novel compounds that are useful in regulating the expression of interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1), and their use in the treatment and/or prevention of cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s). Also, disclosed are compositions comprising the novel compounds, as well as methods for their preparation.
- -
-
Page/Page column 102
(2016/02/05)
-
- METHOD OF SYNTHESIZING BEPOTASTINE OR BENZENESULFONIC ACID SALT THEREOF AND INTERMEDIATES USED THEREIN
-
The present invention relates to a novel method of synthesizing bepotastine or its benzenesulfonic acid salt and novel intermediates used therein. The present invention uses L-α-hydroxy acid for chiral resolution to form an L-α-hydroxy acid salt of a compound represented by the following formula (VII-1), so as to synthesize bepotastine or its benzenesulfonic acid salt in high optical purity.
- -
-
Paragraph 0039; 0040; 0041
(2014/03/21)
-
- TREATMENT OF DISEASES BY EPIGENETIC REGULATION
-
The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of diseases or disorders that are susceptible to administration of a BET inhibitor.
- -
-
Paragraph 0609
(2013/11/05)
-
- KINASE INHIBITORS AND METHODS OF USE
-
The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as mTor, tyrosine kinases, and/or lipid kinases such as PI3 kinase. Also provided in the present invention are methods of using these compositions to modulate activities of one or more of these kinases, especially for therapeutic applications.
- -
-
Page/Page column 84-85
(2010/04/03)
-
- Piperazine- and piperidine-derivatives as melanocortin receptor agonists
-
The present invention relates to melanocortin receptor agonists of formula I, which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction.
- -
-
Page/Page column 40
(2010/02/06)
-
- Design, synthesis and biological evaluation of a novel series of potent, orally active adenosine A1 receptor antagonists with high blood-brain barrier permeability
-
A novel series of 3-(2-substituted-3-oxo-2,3-dihydropyridazin-6-yl) -2-phenylpyrazolo[1,5-a]pyridines (5-38) were synthesized and evaluated for their in vitro adenosine A1 and A2A receptor binding activities, and in vitro metabolism by rat liver in order to search for orally active compounds. Most of the test compounds were potent adenosine A1 receptor antagonists with high A1 selectivity and the A1 affinity and A1 selectivity of carbonyl derivatives (5-11) was particularly high. In particular, compound 7 was an extremely potent and selective adenosine A1 antagonist with high A1 selectivity (Ki=0.026 nM, A2A/A1=5400). In terms of metabolic stability, 2-oxopropyl (5), 2-hydroxypropyl (12), N-methylacetamide (16), 2-(piperidin-1-yl)ethyl (28) and 1-methylpiperidin-4-yl (32, FR194921) were the most stable compounds in this series of analogues. Further in vivo evaluation indicated that compounds 5, 13, 17, 28 and 32 were detected in both plasma and brain after oral administration in rats. In particular, 32 displayed good plasma and brain concentrations (dose: 32mg/kg (n=3); after 30 min, plasma conc.=3390±651 nM, brain conc.=3670±496 nM; after 60 min, plasma conc.=1580±348 nM, brain conc.=2143±434 nM), and a good brain/plasma ratio (1.11±0.060 (30 min), 1.39±0.172 (60 min)). As a result, we could show that 32 is a good candidate for an orally active adenosine A1 receptor antagonist with high blood-brain barrier permeability and good bioavailability (Ki=6.6 nM, A2A/A1=820, BA=60.6±4.9% (32 mg/kg)).
- Kuroda,Takamura,Tenda,Itani,Tomishima,Akahane,Sakane
-
p. 988 - 998
(2007/10/03)
-
- Tetrahydro-isoquinoline-based factor Xa inhibitors
-
Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7- yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K(i) = 21-55 nM but do not inhibit thrombin (K(i) = 5-> 100 μM) and only weakly inhibit trypsin (K(i) = 0.08-5 μM). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.
- Kucznierz, Ralf,Grams, Frank,Leinert, Herbert,Marzenell, Klaus,Engh, Richard A.,Von der Saal, Wolfgang
-
p. 4983 - 4994
(2007/10/03)
-
- N-Acetyl-N-acyl-3-aminoquinazolinones as chemoselective acetylating agents
-
The title compounds, e.g. 3, are highly selective acetylating agents for primary amines in the presence of secondary amines and, in particular, for the less sterically hindered of two different secondary amines.
- Atkinson, Robert S.,Barker, Emma,Sutcliffe, Michael J.
-
p. 1051 - 1052
(2007/10/03)
-
- Piperidinyl and piperazinyl derivatives
-
Compounds of the formula: STR1 in which R1 is alkylsulfonamido of 1 to 6 carbon atoms, arylsulfonamido of 6 to 10 carbon atoms, --NO2,--CN, 1-imidazolyl or 1,2,4-triazol-1-yl; Y is STR2 --CH2 --, --O--, --S--, or --SO2 --; X is --CH= or --N=; R2 is hydrogen when n is 0, otherwise it is hydrogen or --OH; n is one of the integers 0, 1, 2, 3, 4, 5 or 6; A is STR3 where R3 is alkylsulfonamido of 1 to 6 carbons atoms, arylsulfonamido of 6 to 10 carbon atoms, --NO2, --CN, 1-imidazolyl or 1,2,4-triazol-1-yl; or STR4 where R4 is hydrogen or alkyl of 1 to 6 carbon atoms; with the provisos that; a) X is --CH= when Y is STR5 --O-- or --S-- and when Y is STR6 and R2 is --OH; b) X is --N= when A is STR7 c) A is STR8 when Y is --S-- or --SO2 -- and X is --CH=, and their pharmaceutically acceptable salts are Class III antiarrhythmic agents.
- -
-
-
