95652-74-7Relevant articles and documents
Sertraline derivative and preparation method and application thereof
-
Paragraph 0059-0063, (2021/04/14)
The invention discloses a sertraline derivative or a medicinal salt thereof. The structural general formula of the sertraline derivative is shown in the specification. The sertraline derivative has a good inhibition effect on cryptococcus neoformans, particularly, the compound D16 disclosed by the invention has a relatively good inhibition effect on candida glabrata 9073, candida tropicalis 10186, cryptococcus neoformans, candida albicans 5314, candida albicans 904, candida tropicalis 10186, drug-resistant candida albicans 103 and cryptococcus gottii.
A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders
Fischer, Patrick D.,Papadopoulos, Evangelos,Dempersmier, Jon M.,Wang, Zi-Fu,Nowak, Rados?aw P.,Donovan, Katherine A.,Kalabathula, Joann,Gorgulla, Christoph,Junghanns, Pierre P.M.,Kabha, Eihab,Dimitrakakis, Nikolaos,Petrov, Ognyan I.,Mitsiades, Constantine,Ducho, Christian,Gelev, Vladimir,Fischer, Eric S.,Wagner, Gerhard,Arthanari, Haribabu
supporting information, (2021/04/23)
The eukaryotic translation initiation factor 4E (eIF4E) is the master regulator of cap-dependent protein synthesis. Overexpression of eIF4E is implicated in diseases such as cancer, where dysregulation of oncogenic protein translation is frequently observed. eIF4E has been an attractive target for cancer treatment. Here we report a high-resolution X-ray crystal structure of eIF4E in complex with a novel inhibitor (i4EG-BiP) that targets an internal binding site, in contrast to the previously described inhibitor, 4EGI-1, which binds to the surface. We demonstrate that i4EG-BiP is able to displace the scaffold protein eIF4G and inhibit the proliferation of cancer cells. We provide insights into how i4EG-BiP is able to inhibit cap-dependent translation by increasing the eIF4E-4E-BP1 interaction while diminishing the interaction of eIF4E with eIF4G. Leveraging structural details, we designed proteolysis targeted chimeras (PROTACs) derived from 4EGI-1 and i4EG-BiP and characterized these on biochemical and cellular levels. We were able to design PROTACs capable of binding eIF4E and successfully engaging Cereblon, which targets proteins for proteolysis. However, these initial PROTACs did not successfully stimulate degradation of eIF4E, possibly due to competitive effects from 4E-BP1 binding. Our results highlight challenges of targeted proteasomal degradation of eIF4E that must be addressed by future efforts.
4-phenyl-4-oxo-butanoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity
-
, (2008/06/13)
4-phenyl-4-oxo-butanoic acid derivatives for use in the treatment of the human or animal body by therepy; particularly as kynurenine-3-hydroxylase inhibitors, in the prevention and/or treatment of a neurodegenerative disease wherein the inhibition of such an enyzme is needed. The present invention further comprises a selected class of the above mentioned 4-phenyl-4-oxo-butanoic acid derivatives, their pharmaceutically acceptable salts, a process for their preparation and pharmaceutical compositions containing them.
Heterocyclic compounds having tachykinin receptor antagonist activity their preparation and their use
-
, (2008/06/13)
Compounds of the formula and quaternary ammonium ions thereof, wherein R1 and R2 are the same or different and are carbocyclic aryl or aromatic heterocyclic; A is methylene, carbonyl or sulfonyl; B is a single bond, C1-C4 alkylene or C2-C4, alkenylene; D is oxygen; E is C2 alkylene; G is C1-C4 alkylene or C2-C4 alkenylene; and L is -C(R4)(R5), wherein R4 and R5 together with the carbon atom to which they are attached represent a C5-C10 cycloalkyl or a C5-C10 heterocyclic. Especially preferred are compounds wherein L represents wherein J is a C1-C6 alkylene; Ar is a ring carbocyclic or aromatic heterocyclic and S*->O is a sulfoxide in which the sulfur atom is in the 5-configuration. The compounds have tachykinin receptor antagonist activity and exhibit an activity against both the NK1 and NK2 receptors.
Syntheses and antiinflammatory activity of some 6-aryl-2,3,4,5-tetrahydro-3-pyridazinones
Khan,Siddiqui
, p. 614 - 619 (2007/10/03)
6-Aryl-2, 3, 4, 5-tetrahydro-3-pyridazinones (2c-22c) are obtained by dehydrocyclisation of various hydrazides formed by the reaction of appropriate methyl β-aroylpropionate and hydrazine hydrate in the presence of anhydrous sodium acetate. They show promising antiinflammatory activity during their evaluation by carrageenin induced paw edema test in rats.
Combined NK1 and NK2 tachykinin receptor antagonists: Synthesis and structure-activity relationships of novel oxazolidine analogues
Nishi, Takahide,Fukazawa, Tetsuya,Ishibashi, Koki,Nakajima, Katsuyoshi,Sugioka, Yuki,Iio, Yukiko,Kurata, Hitoshi,Itoh, Kazuhiro,Mukaiyama, Osamu,Satoh, Yumiko,Yamaguchi, Takeshi
, p. 875 - 880 (2007/10/03)
We report herein the synthesis and structure-activity relationships of a series of novel oxazolidine analogues with regards to NK1 and NK2 tachykinin receptor binding affinity. Among this series of oxazolidine analogues, some compounds exhibited excellent high binding affinities for both NK1 and NK2 receptors. In addition, we describe the inhibitory effect in vivo on SP-induced airway vascular hyperpermeability and NKA-induced bronchoconstriction in guinea pigs.
Thermal, Three-Carbon + Two-Atom Cycloaddition of Cyclopropenone Ketals with Carbon-Heteroatom Double Bonds: Butenolide, Furan, and γ-Keto Ester Preparation.
Boger, Dale L.,Brotherton, Chistine E.,Georg, Gunda I.
, p. 5615 - 5618 (2007/10/02)
A preliminary study of the thermal reaction of cyclopropenone ketals with carbon-heteroatom double bonds is detailed.The reaction with aldehyde and keto carbonyls provide butenolide ortho esters, the product of a formal three-carbon + two-atom cycloaddition of the cyclopropenone ketal across the carbon-oxygen double bond.