- MITOCHONDRIAL TARGETING COMPOUNDS FOR THE TREATMENT OF ASSOCIATED DISEASES
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Mitochondrial targeting compounds for the treatment of cancer and other disorders associated with mitochondrial function, including diabetes, autoimmune diseases, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases and their preparation. The present invention is also directed to the pharmaceutical compositions and treatment methods, prodrugs based on those compounds and the use thereof.
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Page/Page column 63
(2021/12/08)
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- Discovery and Lead Optimization of Benzene-1,4-disulfonamides as Oxidative Phosphorylation Inhibitors
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Inhibition of oxidative phosphorylation (OXPHOS) is a promising therapeutic strategy for select cancers that are dependent on aerobic metabolism. Here, we report the discovery, optimization, and structure-activity relationship (SAR) study of a series of n
- Dai, Lipeng,Kyani, Armita,Neamati, Nouri,Roy, Joyeeta,Sun, Duxin,Xu, Yibin,Xue, Ding
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- NaI-Catalyzed Oxidative Amination of Aromatic Sodium Sulfinates: Synergetic Effect of Ethylene Dibromide and Air as Oxidants
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A novel NaI-catalyzed oxidative amination of sodium sulfinates, employing both ethylene dibromide (EDB) and air as the oxidants, is described. EDB was first demonstrated to be a promising mild organic oxidant that in air, converted NaI into molecular iodine to promote the cross-coupling reactions of aromatic sodium sulfinates with amines to produce arylsulfonamides. Mechanistic studies indicated that a radical pathway might be involved in the reaction process.
- Fu, Ying,Li, Quan-Zhou,Xu, Qin-Shan,Hügel, Helmut,Li, Ming-Peng,Du, Zhengyin
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supporting information
p. 6966 - 6970
(2018/11/23)
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- Charge-Transfer Complex Promoted Regiospecific C?N Bond Cleavage of Vicinal Tertiary Diamines
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A catalyst-free, charge-transfer complex promoted coupling of sulfonyl chlorides with vicinal tertiary diamines to generate sulfonamides is presented. Mechanistic studies showed that these reactions are proceeded via charge transfer of vicinal tertiary diamines to sulfonyl chlorides, forming the unstable sulfonyl quaternary ammonium like complexes which induced the regiospecific intramolecular C?N bond cleavage of vicinal tertiary diamines. (Figure presented.).
- Fu, Ying,Xu, Qin-Shan,Shi, Chun-Zhao,Du, Zhengyin,Xiao, Caiqin
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supporting information
p. 3502 - 3506
(2018/09/14)
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- NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION, FOR PREVENTING OR TREATING INFLAMMATORY DISEASES, COMPRISING SAME AS ACTIVE INGREDIENT
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The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, comprising same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.
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Paragraph 0102
(2018/06/07)
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- Eosin Y-Sensitized Photocatalytic Reaction of Tertiary Aliphatic Amines with Arenesulfonyl Chlorides under Visible-Light Irradiation
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A mild, practical, and environmentally friendly route to vinyl sulfones and sulfonamides has been developed based on the reaction of aliphatic amines with arenesulfonyl chlorides in the presence of eosin Y as a photocatalyst under visible light. The method permits the selective formation of vinyl sulfones or sulfonamides, depending on the oxidation environment and solvent. A wide range of products were obtained in moderate to good yields under the optimized conditions.
- Cai, Yuguo,Zhang, Ronghua,Sun, Deli,Xu, Song,Zhou, Qiguang
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p. 1630 - 1635
(2017/08/11)
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- I2/TBHP Mediated C-N and C-H Bond Cleavage of Tertiary Amines toward Selective Synthesis of Sulfonamides and β-Arylsulfonyl Enamines: The Solvent Effect on Reaction
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A novel method toward synthesis of sulfonamides and β-arylsulfonyl enamines has been developed via I2/TBHP mediated C-N and C-H bond cleavage of tertiary amines, which features highly selective formation of two different target products depending on the reaction solvent. The experimental results reveal that H2O as the solvent could effectively achieve the C-N bond cleavage to produce sulfonamides due to H2O participating in the reaction process where H2O plays a dual role. Differing from H2O, organic solvents (such as dimethyl sulfoxide) could promote the C-H bond cleavage of tertiary amines to yield β-arylsulfonyl enamines.
- Lai, Junyi,Chang, Liming,Yuan, Gaoqing
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supporting information
p. 3194 - 3197
(2016/07/14)
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- Synthesis of sulfonamides: Via copper-catalyzed oxidative C-N bond cleavage of tertiary amines
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A copper-catalyzed coupling reaction of sulfonyl chlorides with tertiary amines via the oxidative C-N bond cleavage of tertiary amines was developed. Sulfonamides were synthesized using this strategy in moderate to good yields. The reaction was applicable to various tertiary amines, as well as sulfonyl chlorides.
- Ji, Jing,Liu, Zhengyi,Liu, Ping,Sun, Peipei
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p. 7018 - 7023
(2016/07/30)
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- Metal-free synthesis of sulfonamides via iodine-catalyzed oxidative coupling of sulfonyl hydrazides and amines
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A novel, rapid, and environmentally-friendly protocol for the synthesis of sulfonamides using iodine as catalyst under solvent-free conditions is described. This method involves the oxidative coupling of sulfonyl hydrazides and amines in the presence of catalytic amount of iodine using TBHP as oxidant. This protocol does not require purification techniques such as column chromatography and recrystalization.
- Parumala, Santosh Kumar Reddy,Peddinti, Rama Krishna
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supporting information
p. 1232 - 1235
(2016/03/01)
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- ACYCLIC CYANOETHYLPYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS
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The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
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Page/Page column 54
(2014/10/03)
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- NAPHTHYLACETIC ACIDS
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The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts and esters thereof, wherein X, Q, and R1-R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 82
(2010/06/15)
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- Synthesis and PKCθ inhibitory activity of a series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles
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A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and evaluated as PKCθ inhibitors. Optimization resulted in the identification of compound 15 with an IC50 value 0.44 nM for the inhibition of PKCθ with 150-fold select
- Shim, Jaechul,Eid, Clark,Lee, Julie,Liu, Erica,Chaudhary, Divya,Boschelli, Diane H.
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scheme or table
p. 6575 - 6577
(2010/06/12)
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- ARYL SULFONAMIDES USEFUL FOR MODULATION OF THE PROGESTERONE RECEPTOR
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In one embodiment, compounds of the following structure are described, wherein R1 to R7 are described herein. Also provided are methods for preparing these compounds and methods of contraception; treating or preventing fibroids; trea
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Page/Page column 10
(2008/12/08)
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- Facile one-pot synthesis of aromatic and heteroaromatic sulfonamides
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A series of arene and heteroarene sulfonamides were prepared in one vessel from aryl and heteroaryl bromides via conversion into the corresponding Grignard reagents using either magnesium or isopropylmagnesium chloride and subsequent reaction with sulfur dioxide, sulfuryl chloride, and an amine.
- Pandya, Rina,Murashima, Takashi,Tedeschi, Livio,Barrett, Anthony G. M.
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p. 8274 - 8276
(2007/10/03)
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- Antileishmanial activities of several classes of aromatic dications
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Aromatic dicationic molecules possess impressive activity against a broad spectrum of microbial pathogens, including Pneumocystis carinii, Cryptosporidium parvum, and Candida albicans. In this work, 58 aromatic cations were examined for inhibitory activity against axenic amastigote-like Leishmania donovani parasites. In general, the most potent of the compounds were substituted diphenyl furan and thiophene dications. 2,5-Bis-(4-amidinophenyl)thiophene was the most active compound. This agent displayed a 50% inhibitory concentration (IC50) of 0.42 ± 0.08 μM against L. donovani and an in vitro antileishmanial potency 6.2-fold greater than that of the clinical antileishmanial dication pentamidine and was 155-fold more toxic to the parasites than to a mouse macrophage cell line. 2,4-Bis-(4-amidinopheny)furan was twice as active as pentamidine (IC50, 1.30 ± 0.21 μM), while 2,5-bis-(4-amidinopheny)furan and pentamidine were essentially equipotent in our in vitro antileishmanial assay. Carbazoles, dibenzofurans, dibenzothiophenes, and benzimidazoles containing amidine or substituted amidine groups were generally less active than the diphenyl furans and thiophenes. In all cases, aromatic dications possessing strong antileishmanial activity were severalfold more toxic to the parasites than to a cultured mouse macrophage cell line. These structure-activity relationships demonstrate the potent antileishmanial activity of several aromatic dications and provide valuable information for the future design and synthesis of more potent antiparasitic agents.
- Brendle, James J.,Outlaw, Abram,Kumar, Arvind,Boykin, David W.,Patrick, Donald A.,Tidwell, Richard R.,Werbovetz, Karl A.
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p. 797 - 807
(2007/10/03)
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- New diarylmethylpiperazines as potent and selective nonpeptidic δ opioid receptor agonists with increased in vitro metabolic stability
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Nonpeptide δ opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human δ receptor (IC50 = 11 nM, μ/δ = 740, κ/δ > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for δ receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for δ binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)-methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, μ/δ = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.
- Plobeck,Delorme,Wei,Yang,Zhou,Schwarz,Gawell,Gagnon,Pelcman,Schmidt,Yue,Walpole,Brown,Zhou,Labare,Payza,St-Ogne,Kamassah,Morin,Projean,Ducharme,Roberts
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p. 3878 - 3894
(2007/10/03)
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- Linear Free Energy Relationship Studies of 5-Substituted 2,4-Dioxopyrimidine Nucleosides
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The development of a direct and efficient palladium(0)-catalyzed biaryl coupling reaction permitted the synthesis of a series of N1-substituted 5-aryl-2,4-dioxopyrimidines.The physical and spectral properties of these compounds were determined and correlated by various linear free energy relationships.The relationships between the physical and spectral data with Hammett ? constants proved useful in analyzing the electron distribution of the heterocycle.Although a significant degree of orbital overlap and interaction between the substituents and the pyrimidine ring was observed, it is doubtful that the interactions are comparable to those of a benzene ring system.
- Chang, George,Mertes, Mathias P.
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p. 3625 - 3631
(2007/10/02)
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