- NOVEL COMPOUND HAVING HSP90 INHIBITORY ACTIVITY OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND MEDICAL USE THEREOF
-
The present invention relates to a novel compound having HSP90 inhibitory activity or a pharmaceutically acceptable salt thereof, and a medicinal use thereof, and composition comprising a dihydroxyphenyl compound or a benzamide compound, which is a novel compound having the HSP90 inhibitory activity of the present invention can effectively inhibit HSP90, and thus can be usefully used as a pharmaceutical composition for preventing or treating HSP90-mediated diseases or a health functional food for preventing or improving HSP90-mediated diseases, which selected from the group consisting of cancer diseases, degenerative neurological diseases and viral infections.
- -
-
Paragraph 0250; 0251
(2019/02/13)
-
- Selective synthesis of mono- and di-methylated amines using methanol and sodium azide as C1 and N1 sources
-
A Ru(ii) complex mediated synthesis of various N,N-dimethyl and N-monomethyl amines from organic azides using methanol as a methylating agent is reported. This methodology was successfully applied for a one-pot reaction of bromide derivatives and sodium azide in methanol. Notably, by controlling the reaction time several N-monomethylated and N,N-dimethylated amines were synthesized selectively. The practical applicability of this tandem process was revealed by preparative scale reactions with different organic azides and synthesis of an anti-vertigo drug betahistine. Several kinetic experiments and DFT studies were carried out to understand the mechanism of this transformation.
- Chakrabarti, Kaushik,Mishra, Anju,Panja, Dibyajyoti,Paul, Bhaskar,Kundu, Sabuj
-
supporting information
p. 3339 - 3345
(2018/07/29)
-
- Selective Monomethylation of Amines with Methanol as the C1 Source
-
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
- Choi, Geunho,Hong, Soon Hyeok
-
supporting information
p. 6166 - 6170
(2018/04/30)
-
- 4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors
-
Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.
- Pechulis, Anthony D.,Beck, James P.,Curry, Matt A.,Wolf, Mark A.,Harms, Arthur E.,Xi, Ning,Opalka, Chet,Sweet, Mark P.,Yang, Zhicai,Vellekoop, A. Samuel,Klos, Andrew M.,Crocker, Peter J.,Hassler, Carla,Laws, Mia,Kitchen, Douglas B.,Smith, Mark A.,Olson, Richard E.,Liu, Shuang,Molino, Bruce F.
-
p. 7219 - 7222
(2013/01/15)
-
- INDAZOLEPROPIONIC ACID AMIDE COMPOUND
-
Disclosed is a compound which is useful in preventing and treating cardiac arrhythmia such as atrial fibrillation. A compound represented by formula (1) or a pharmaceutically acceptable salt of the same. In formula (1), ring X represents benzene or pyridine; R1 represents an optionally substituted alkyl group; R2 represents an optionally substituted aryl group, an optionally substituted heterocyclic group, an optionally substituted arylalkyl group or an optionally substituted heterocyclic group-substituted alkyl group; R3, R4, R5, R6, R7, R8 and R9 represent each hydrogen or an alkyl group, provided that R3 and R5 may be bonded to each other to form, together with the carbon atom adjacent thereto, a cycloalkyl group; and m represents 0 or 1.
- -
-
Page/Page column 41-42
(2012/02/01)
-
- Highly enantioselective synthesis of tetrahydroquinolines via cobalt(II)-catalyzed tandem 1,5-hydride transfer/cyclization
-
A chiral catalyst prepared from N,N′-dioxide and Co(BF 4)2·6H2O was applied in the asymmetric hydride transfer initiated cyclization reaction, giving optically active tetrahydroquinolines in good yields with high enantioselectivities under mild reaction conditions. Meanwhile, in light of the absolute configuration of the product, a possible working model was proposed to explain the origin of the activation and asymmetric induction.
- Cao, Weidi,Liu, Xiaohua,Wang, Wentao,Lin, Lili,Feng, Xiaoming
-
p. 600 - 603
(2011/04/15)
-
- Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: Discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl- benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia
-
In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzyl- carbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.
- Pfefferkorn, Jeffrey A.,Choi, Chulho,Larsen, Scott D.,Auerbach, Bruce,Hutchings, Richard,Park, William,Askew, Valerie,Dillon, Lisa,Hanselman, Jeffrey C.,Lin, Zhiwu,Lu, Gina H.,Robertson, Andrew,Sekerke, Catherine,Harris, Melissa S.,Pavlovsky, Alexander,Bainbridge, Graeme,Caspers, Nicole,Kowala, Mark,Tait, Bradley D.
-
-
- Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-ones
-
In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000-fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases.
- Piazzi, Lorna,Belluti, Federica,Bisi, Alessandra,Gobbi, Silvia,Rizzo, Stefano,Bartolini, Manuela,Andrisano, Vincenza,Recanatini, Maurizio,Rampa, Angela
-
p. 575 - 585
(2008/03/12)
-
- Formation of benzylamines from triazene compounds via a 1,2-proton shift
-
A new approach to benzylamines using triazene compounds has been developed that is facilitated by the lithiation of aryltriazenes followed by treatment with an electrophile. The regioselectivity of the reaction can be controlled by means of the substituents in the aryl group. The reaction contains the following steps: intramolecular carbon-carbon bond formation involving lithiation of an alkyl group on a 3-nitrogen atom; a 1,2-proton shift; and the subsequent release of nitrogen gas. Through the use of a deuterated triazene, we were able to determine that the reaction proceeds through a 1,2-proton shift.
- Nishiwaki, Keiji,Ogawa, Takashi,Shigeta, Kazumi,Takahashi, Koichi,Matsuo, Keizo
-
p. 7034 - 7042
(2007/10/03)
-
- TACHYKININ RECEPTOR ANTAGONISTS
-
The present invention relates to selective NK-1 receptor antagonists of Formula (I) or a pharmaceutically acceptable salt thereof, for the treatment of disorders associated with an excess of tachykinins.
- -
-
-
- DPP-IV INHIBITORS
-
The invention relates to compounds of formula (I), Z-C(R1R 2)-C(R3NH2)-C(R4R5)-X-N(R 6R7), wherein Z, R1-7 and X have the meaning as cited in the description and the claims. Said compounds are useful as DPP-lV inhibitors. The invention also relates to the
- -
-
Page/Page column 41
(2010/02/14)
-
- α-lithiation of 1-Aryl-3,3-dialkyltriazenes and intramolecular conversion to benzylamine and tetrahydrobenzotriazine derivatives
-
An alternative route to benzylamine derivatives is provided by the lithiation of aryltriazenes followed by treatment with an electrophile [Eq. (1)]. The regioselectivity of the reaction can be controlled by means of the substituents X. When the 2- and 6-p
- Nishiwaki, Keiji,Ogawa, Takashi,Matsuo, Keizo
-
p. 484 - 486
(2007/10/03)
-
- Oxidations with Cerium(IV) Sulfate: Intramolecular Cyclization of N-Benzyl-&β-aminoketones Yielding 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines
-
Preparation and regiospecific cerium(IV) sulfate of the substituted N-benzyl-β-aminoketones 3 are described. 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines 4 so obtained are reduced by sodium borohydride.
- Holzgrabe, Ulrike
-
p. 647 - 654
(2007/10/02)
-