- EGFR PROTEOLYSIS TARGETING CHIMERIC MOLECULES AND ASSOCIATED METHODS OF USE
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an E3 ubiquitin ligase and on the other end a moiety which binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effectuate ubiquitination, and therefore, degradation (and inhibition) of the target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
- -
-
Paragraph 001010; 101011
(2018/07/29)
-
- TRIAZOLE ACC INHIBITORS AND USES THEREOF
-
The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
- -
-
Paragraph 0567-0569
(2017/07/06)
-
- HEXAHYDROPYRAZINOBENZ- OR -PYRIDO-OXAZEPINES CARRYING AN OXYGEN-CONTAINING SUBSTITUENT AND USE THEREOF IN THE TREATMENT OF 5-HT2C-DEPENDENT DISORDERS
-
The present invention relates to compound of formula (I) (I) wherein the variables are as defined in the claims and the description. The invention further relates to a pharmaceutical composition containing such compounds, to their use as modulators, espec
- -
-
Page/Page column 78
(2017/06/27)
-
- SULFAMATE DERIVATIVE COMPOUNDS FOR USE IN TREATING OR ALLEVIATING PAIN
-
The present invention relates to sulfamate derivative compounds and a composition for treating and/or alleviating pain containing the sulfamate derivative compounds or a pharmaceutically acceptable salt thereof as an active ingredient. More specifically,
- -
-
Page/Page column 90
(2015/06/25)
-
- Enantioselective copper-catalyzed intramolecular phenolic O-H bond insertion: Synthesis of chiral 2-carboxy dihydrobenzofurans, dihydrobenzopyrans, and tetrahydrobenzooxepines
-
Efficient: A copper-catalyzed enantioselective intramolecular insertion of carbenoids into phenolic O-H bonds has been developed. This method can be used for the synthesis of the title compounds in high yields and excellent enantioselectivities under mild and neutral conditions (see scheme). NaBAr F=sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. Copyright
- Song, Xiao-Guang,Zhu, Shou-Fei,Xie, Xiu-Lan,Zhou, Qi-Lin
-
supporting information
p. 2555 - 2558
(2013/04/10)
-
- Practical asymmetric catalytic synthesis of spiroketals and chiral diphosphine ligands
-
A practical procedure has been developed for efficient synthesis of chiral aromatic spiroketals and the relevant diphosphine ligands. The procedure includes first asymmetric hydrogenation of readily available α, α'-bis(2-benzyloxyarylidene) ketones cat-al
- Wang, Xiaoming,Wang, Xubin,Guo, Peihua,Wang, Zheng,Ding, Kuiling
-
supporting information
p. 2900 - 2907
(2014/03/21)
-
- Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation
-
A series of 2′-benzyloxy-5′-substituted-5-benzylidene- thiazolidine-2,4-thione and -dione derivatives was synthesized and evaluated as inhibitors of translation initiation. In an effort to generate novel translation initiation inhibitors for cancer therapy, a series of 2′-benzyloxy- 5′-substituted-5-benzylidene-thiazolidine-2,4-thione and dione derivatives was synthesized and evaluated for activity in translation initiation specific assays. Several candidates of the 5-benzylidene-thiazolidine-2,4-diones (3c, 3d, and 3f) and -thiones (2b, 2e, and 2j), inhibit cell growth with low μM GI50 mediated by inhibition of translation initiation, which involves partial depletion of intracellular Ca2+ stores and strong phosphorylation of eIF2Iα.
- Chen, Han,Fan, Yun-Hua,Natarajan, Amarnath,Guo, Yuhong,Iyasere, Julia,Harbinski, Fred,Luus, Lia,Christ, William,Aktas, Huseyin,Halperin, Jose A.
-
p. 5401 - 5405
(2007/10/03)
-
- Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines
-
A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activation of these compounds at serotonin receptor subtypes. The target compounds were evaluated using in vivo behavioral assays for hallucinogen-like and 5-HT(1A) agonist activity and in vitro radioligand competition assays for their affinity at 5-HT(2A), 5-HT(2C), and 5-HT(1A) receptor sites. Functional activity at the 5-HT(2A) receptor was determined for all compounds. In addition, for some compounds functional activity was determined at the 5-HT(1A) receptor. Hallucinogen-like activity, evaluated in the two-lever drug discrimination paradigm using LSD-trained rats, was attenuated or abolished for all of the fluorinated analogues. One of the tryptamines, 4-fluoro-5-methoxy-DMT (6), displayed high 5-HT(1A) agonist activity, with potency greater than that of the 5-HT(1A) agonist 8-OH-DPAT. The ED50 of 6 in the two-lever drug discrimination paradigm using rats trained to discriminate the 5-HT(1A) agonist LY293284 was 0.17μmol/kg, and the K(i) at [3H]8-OH-DPAT-labeled 5-HT(1A) receptors was 0.23 nM. The results indicate that fluorination of hallucinogenic tryptamines generally has little effect on 5-HT(2A/2C) receptor affinity or intrinsic activity. Affinity at the 5-HT(1A) receptor was reduced, however, in all but one example, and all of the compounds tested were full agonists but with reduced functional potency at this serotonin receptor subtype. The one notable exception was 4-fluoro-5-methoxy-DMT (6), which had markedly enhanced 5-HT(1A) receptor affinity and functional potency. Although it is generally considered that hallucinogenic activity results from 5-HT(2A) receptor activation, the present results suggest a possible role for involvement of the 5-HT(1A) receptor with tryptamines.
- Blair,Kurrasch-Orbaugh,Marona-Lewicka,Gumbay,Watts,Barker,Nichols
-
p. 4701 - 4710
(2007/10/03)
-