32366-02-2Relevant articles and documents
INHIBITORS OF ALPHA 2 BETA 1 INTEGRIN AND METHODS OF USE THEREOF
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Paragraph 0724; 1031-1033; 1243-1245, (2021/11/06)
Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.
Stabilization of Azapeptides by Namide···H-NamideHydrogen Bonds
Baruah, Kalpita,Sahariah, Biswajit,Sakpal, Sushil S.,Deka, Jugal Kishore Rai,Bar, Arun Kumar,Bagchi, Sayan,Sarma, Bani Kanta
supporting information, p. 4949 - 4954 (2021/06/28)
An unusual Namide···H-Namide hydrogen bond (HB) was previously proposed to stabilize the azapeptide β-Turns. Herein we provide experimental evidence for the Namide···H-Namide HB and show that this HB endows a stabilization of 1-3 kcal·mol-1 and enforces the trans-cis-Trans (t-c-T) and cis-cis-Trans (c-c-T) amide bond conformations in azapeptides and N-methyl-Azapeptides, respectively. Our results indicate that these Namide···H-Namide HBs can have stabilizing contributions even in short azapeptides that cannot fold to form β-Turns.
Cannabidiol carbamate compound, pharmaceutical preparation, preparation method and application
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Paragraph 0055-0059, (2021/01/30)
The invention relates to a cannabidiol carbamate compound, a medicinal preparation, a preparation method and application, and belongs to the field of compounds for treating and preventing diseases related to aging, Alzheimer's disease and Parkinson's disease. The compound has a structure shown as a formula I or a pharmaceutically acceptable salt of the structure shown as the formula I. The compound has good butyrylcholine esterase resisting activity, shows good application prospect in treatment of Alzheimer's disease, and shows good application potential.
Novel cannabidiol?carbamate hybrids as selective BuChE inhibitors: Docking-based fragment reassembly for the development of potential therapeutic agents against Alzheimer's disease
Jiang, Xia,Liu, Xin-Hua,Shi, Jingbo,Tang, Wenjian,Wang, Sheng,Wu, Chengyao,Xu, Yingying,Zha, Liang,Zhang, Jing,Zhang, Ziwen,Zuo, Jiawei
, (2021/08/10)
Cannabidiol (CBD) and rivastigmine have been launched as drugs for treating dementia and cholinesterases (ChEs) are ideal drug targets. This study focused on developing novel ChE inhibitors as drug leads against dementia through molecular modeling and fragment reassembly approaches. A potent carbamate fragment binding to active site gorge of BuChE was found via a docking-based structural splicing approach, thus, 17 novel compounds were designed by structural reassembly. Compound C16 was identified as a highly selective potent BuChE inhibitor (IC50 = 5.3 nM, SI > 4000), superior to CBD (IC50 = 0.67 μM). C16 possessed BBB penetrating ability, benign safety, neuroprotection, antioxidant and pseudo-irreversible BuChE inhibition (Kd = 13 nM, k2 = 0.26 min?1), showing good drug-like properties. In vivo studies confirmed that C16 significantly ameliorated the scopolamine-induced cognition impairment, almost entirely recovered the Aβ1?42 (icv)-impaired cognitive function to the normal level, showed better behavioral performance than donepezil and good anti-amyloidogenic effect. Hence, the potential BuChE inhibitor C16 can be developed as a promising disease-modifying treatment of AD.
STING PYRAZOLE AGONISTS AND USES THEREOF
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Paragraph 00470-00471, (2020/07/14)
The present invention provides compounds, compositions thereof, and methods of using the same for the modulation of STING, and the treatment of STING-mediated disorders.
1-Cyanoformamidines. Formation during the RuO4-mediated oxidation of secondary amines
Florea, Cristina,Stavarache, Cristina,Petride, Horia
, p. 319 - 325 (2016/10/11)
When performed in the presence of cyanide and at pH smaller than 5, the RuO4-mediated oxidation of secondary amines Bn-NH-R (1a-b; R=Me, Et) gave mainly 1-cyanoformamidines Bn-NR-C(=NH)-CN (2a-b) and their hydrolysis products Bn-NR-COCN (3a-b), Bn-NR-CN (4a-b), Bn-NR-CONH2 (5a-b). Carboxamides 5a-b can result also directly from 1a-b. (Chemical Equation Presented).
Medium-Ring Nitrogen Heterocycles through Migratory Ring Expansion of Metalated Ureas
Hall, Jessica E.,Matlock, Johnathan V.,Ward, John W.,Gray, Katharine V.,Clayden, Jonathan
supporting information, p. 11153 - 11157 (2016/10/13)
Simple benzo-fused nitrogen heterocycles (indolines, tetrahydroquinolines, and their homologues) undergo migratory ring expansion through deprotonation of their benzylic urea derivatives with lithium diisopropylamide (LDA) in the presence of N,N′-dimethyl
Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors
Patel, Jayendra Z.,Nevalainen, Tapio J.,Savinainen, Juha R.,Adams, Yahaya,Laitinen, Tuomo,Runyon, Robert S.,Vaara, Miia,Ahenkorah, Stephen,Kaczor, Agnieszka A.,Navia-Paldanius, Dina,Gynther, Mikko,Aaltonen, Niina,Joharapurkar, Amit A.,Jain, Mukul R.,Haka, Abigail S.,Maxfield, Frederick R.,Laitinen, Jarmo T.,Parkkari, Teija
, p. 253 - 265 (2015/02/05)
At present, inhibitors of α/β-hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5-thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4-morpholino-1,2,5-thiadiazol-3-yl cyclooctyl(methyl)carbamate (JZP-430) potently and irreversibly inhibited hABHD6 (IC50 = 44 nM) and showed ～ 230-fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off-targets of related compounds. Additionally, activity-based protein profiling indicated that JZP-430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP-430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.
Carbamoyl radicals from carbamoylxanthates: a facile entry into isoindolin-1-ones
López-Valdez, Germán,Olguín-Uribe, Simón,Miranda, Luis D.
, p. 8285 - 8289 (2008/03/30)
It has been found that carbamoylxanthates derived from secondary t-butyl amines are stable compounds which function as efficient sources of carbamoyl radicals. The carbamoylxanthates derived from t-butylbenzylamines can be efficiently transformed into 2-t
β-lactam derivatives as inhibitors of human cytomegalovirus protease
Yoakim, Christiane,Ogilvie, William W.,Cameron, Dale R.,Chabot, Catherine,Guse, Ingrid,Haché, Bruno,Naud, Julie,O'Meara, Jeff A.,Plante, Raymond,Déziel, Robert
, p. 2882 - 2891 (2007/10/03)
The development of novel monobactam inhibitors of HCMV protease incorporating a carbon side chain at C-4 and a urea function at N-1 is described. Substitution with small groups at the C-3 position of the β- lactam ring gave an increase in enzymatic activity and in stability; however, a lack of selectivity against other serine proteases was noted. The use of both triand tetrasubstituted urea functionalities gave effective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing groups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.
