- Process development of a novel anti-inflammatory agent. The regiospecific bromination of 4′-acetylmethanesulfonanilide
-
An efficient, practical synthesis of a novel antiinflammatory agent (FK3311, 1) which is acceptable environmentally and could be used for pilot plant manufacture is described. Regiospecific bromination of 4′-acetylmethanesulfonanilide, allowing selective side chain or nuclear halogenation, also has been investigated. Development efforts focused on the optimized Ullmann coupling reaction conditions and the isolation and purification of 1 to give satisfactory quality product (99.8% purity) according to the new and concise synthetic route.
- Zanka, Atsuhiko,Kubota, Ariyoshi,Hirabayashi, Satoshi,Nakamura, Hitoshi
-
-
Read Online
- Synthesis, biological evaluation and molecular docking of new sulfonamide-based indolinone derivatives as multitargeted kinase inhibitors against leukemia
-
Series of novel sulfonamide-based 3-indolinones 3a-m and 4a-f were designed, synthesized and then their cytotoxic activity was evaluated against a panel of sixty cancer cell lines. This screening indicated that 4-(2-(5-fluoro-2-oxoindolin-3-ylidene)acetyl)phenyl benzenesulfonate (4f) possessed promising cytotoxicity against CCRF-CEM and SR leukemia cell lines with IC50 values 6.84 and 2.97 μM, respectively. Further investigation of the leukemic cytotoxicity of compound 4f was carried out by performing PDGFRα, VEGFR2, Aurora A/B and FLT3 enzyme assays and CCRF-CEM and SR cell cycle analysis. These investigations showed that compound 4f exhibited pronounced dual inhibition of both kinases PDGFRα and Aurora A with potency of 24.15 and 11.83 nM, respectively. The in vitro results were supported by molecular docking studies in order to explore its binding affinity and its key amino acids interactions. This work represents compound 4f as a promising anticancer agent against leukemia.
- El-Hussieny, Marwa,El-Sayed, Naglaa F.,Fouad, Marwa A.,Ewies, Ewies F.
-
-
- COUP-TFII RECEPTOR INHIBITORS AND METHODS USING SAME
-
The invention relates in one aspect to the identification of compounds that inhibit COUP-TFII activity. In certain embodiments, the compounds of the invention have submicromolar activity against COUP-TFII. In other embodiments, the compounds of the invention have no measurable effect on COUP-TFII-negative cells. In yet other embodiments, the compounds of the invention inhibiting prostate tumor growth in a subject without significant effect on the subject's body weight.
- -
-
Page/Page column 40
(2019/12/04)
-
- Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
-
Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti-proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 μM to 0.81 μM against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies.
- Li, Ridong,Ning, Xianling,Zhou, Shuo,Lin, Zhiqiang,Wu, Xingyu,Chen, Hong,Bai, Xinyu,Wang, Xin,Ge, Zemei,Li, Runtao,Yin, Yuxin
-
-
- Photochemistry of N-Arylsulfonimides: An Easily Available Class of Nonionic Photoacid Generators (PAGs)
-
The photochemical behavior of differently substituted N-arylsulfonimides was investigated. Homolysis of the S?N bond took place as the exclusive path from the singlet state to afford both N-arylsulfonamides and photo-Fries adducts, the amount of which depended on reaction conditions and aromatic substituents. Sulfinic and sulfonic acids were released upon irradiation under deaerated and oxygenated conditions, respectively. The nature of the excited states and intermediates involved were proved by laser flash photolysis and EPR experiments. These results highlighted the potential of such compounds as nonionic photoacid generators able to photorelease up to two equivalents of a strong acid for each mole of substrate.
- Torti, Edoardo,Protti, Stefano,Merli, Daniele,Dondi, Daniele,Fagnoni, Maurizio
-
supporting information
p. 16998 - 17005
(2016/11/16)
-
- Cascade Michael-Aldol reaction: Efficient annulation of sulfonamide chalcones into novel cyclohexenones under solvent-free conditions
-
A simple, convenient and efficient synthesis of novel sulfonamide cyclohexenones from differently substituted sulfonamide chalcones has been developed. Syntheses of cyclohexenones have been achieved via cascade Michael-Aldol reaction under solvent free condition. This process features mild and solvent-free synthesis of the titled compounds with high yields (18 examples, up to 95% yield). The synthesized scaffold is a promising intermediate for the further transformation into various heterocyclic compounds.
- Agrawal, Nikita R.,Bahekar, Sandeep P.,Agrawal, Abhijeet R.,Sarode, Prashant B.,Chandak, Hemant S.
-
p. 227 - 245
(2016/07/06)
-
- Palladium-Catalyzed, Ring-Forming Aromatic C-H Alkylations with Unactivated Alkyl Halides
-
A catalytic C-H alkylation using unactivated alkyl halides and a variety of arenes and heteroarenes is described. This ring-forming process is successful with a variety of unactivated primary and secondary alkyl halides, including those with β-hydrogens. In contrast to standard polar or radical cyclizations of aromatic systems, electronic activation of the substrate is not required. The mild, catalytic reaction conditions are highly functional group tolerant and facilitate access to a diverse range of synthetically and medicinally important carbocyclic and heterocyclic systems.
- Venning, Alexander R. O.,Bohan, Patrick T.,Alexanian, Erik J.
-
supporting information
p. 3731 - 3734
(2015/04/14)
-
- Installation of protected ammonia equivalents onto aromatic & heteroaromatic rings in water enabled by micellar catalysis
-
A single set of conditions consisting of a palladium catalyst, a commercially available ligand, and a base, allow for several types of C-N bond constructions to be conducted in water with the aid of a commercially available "designer" surfactant (TPGS-750-M). Products containing a protected NH2 group in the form of a carbamate, sulfonamide, or urea can be fashioned starting with aryl or heteroaryl bromides, iodides, and in some cases, chlorides, as substrates. Reaction temperatures are in the range of room temperature to, at most, 50 °C, and result in essentially full conversion and good isolated yields.
- Isley, Nicholas A.,Dobarco, Sebastian,Lipshutz, Bruce H.
-
supporting information
p. 1480 - 1488
(2014/03/21)
-
- Design, synthesis and structure-activity relationship studies of novel and diverse cyclooxygenase-2 inhibitors as anti-inflammatory drugs
-
Because of the pivotal role of cyclooxygenase (COX) in the inflammatory processes, non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of inflammatory diseases/syndromes; however, traditional NSAIDs exhibit serious side-effects such as gastrointestinal damage and hyper sensitivity owing to their COX-1 inhibition. Also, COX-2 inhibition-derived suppressive or preventive effects against initiation/proliferation/invasion/motility/recurrence/metastasis of various cancers/tumours such as colon, gastric, skin, lung, liver, pancreas, breast, prostate, cervical and ovarian cancers are significant. In this study, design, synthesis and structure-activity relationship (SAR) of various novel {2-[(2-, 3- and/or 4-substituted)-benzoyl, (bicyclic heterocycloalkanophenyl)carbonyl or cycloalkanecarbonyl]-(5- or 6-substituted)-1H-indol-3-yl}acetic acid analogues were investigated to seek and identify various chemotypes of potent and selective COX-2 inhibitors for the treatment of inflammatory diseases, resulting in the discovery of orally potent agents in the peripheral-inflammation model rats. The SARs and physicochemical properties for the analogues are described as significant findings. For graphical abstract: see Supplementary Material. (www.informahealthcare.com/enz)
- Hayashi, Shigeo,Ueno, Naomi,Murase, Akio,Takada, Junji
-
p. 846 - 867
(2015/02/19)
-
- α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists
-
A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant.
- Kim, Ho Shin,Jin, Mi-Kyoung,Kang, Sang-Uk,Lim, Ju-Ok,Tran, Phuong-Thao,Hoang, Van-Hai,Ann, Jihyae,Ha, Tae-Hwan,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Blumberg, Peter M.,Lee, Jeewoo
-
p. 2685 - 2688
(2014/06/09)
-
- Synthesis, anti-inflammatory and antioxidant activity of ring-a-monosubstituted chalcone derivatives
-
A library of ring-A-monosubstituted chalcone derivatives (4a-4i, 5a and 5b) was designed and synthesised. The structures as well as the identities of these compounds were established on the basis of spectral (1H NMR, 13C NMR, FT-IR and Mass) and elemental (C, H, N) analyses. All the derivatives were evaluated for their anti-inflammatory and antioxidant activities in vitro using the inhibition of protein denaturation and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, respectively. The results indicated a promising anti-inflammatory activity for most of the synthesised compounds with many derivatives showing activities similar to or greater than that of the standard. The sulphonamide-substituted chalcones 4h, 4i, 5a and 5b were found to be the most active derivatives across the concentration range tested. However, all the derivatives exhibited rather mild antioxidant activity compared to the ascorbic acid standard. Interestingly, it was observed that the unsubstituted parent chalcone was one of the optimal compounds with only the trifluoromethyl analogue 4a showing better activity as an antioxidant. The two regioisomeric aminochalcones and 4′-cyanochalcone 4b also seemed to possess decent antioxidant potential.
- Iqbal, Hiba,Prabhakar, Visakh,Sangith, Atul,Chandrika, Baby,Balasubramanian, Ranganathan
-
p. 4383 - 4394
(2015/04/22)
-
- α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists
-
A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant.
- Kim, Ho Shin,Jin, Mi-Kyoung,Kang, Sang-Uk,Lim, Ju-Ok,Tran, Phuong-Thao,Hoang, Van-Hai,Ann, Jihyae,Ha, Tae-Hwan,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Blumberg, Peter M.,Lee, Jeewoo
-
p. 2685 - 2688
(2015/02/19)
-
- Asymmetric reduction of N-[4-(2-bromoacetyl)phenyl]methanesulfonamide by employing Candida viswanathii MTCC 5158
-
Enantioselective synthesis of chiral drugs by chemoenzymatic processes have attracted attention in which the crucial stereogenic step involves an enzymatic reaction by virtue of chemo-, regio- and enantio- selectivity and eco-friendly nature of biocatalysis, (S)-sotalol a β-blocker, belongs to class-III antiarrhythmic agents. To avoid the side effects of racemic sotalol, efforts have been put forward to synthesize a key intermediate for the synthesis of (S)-enantiomer of sotalol, which is more potent than the (R)-enantiomer. The aryl ketone, N-(4-acetyl-phenyl) methanesulfonamide was synthesized from the initial substrate 4-aminoacetophenone. Further, the bromination of aryl ketone was carried out to obtain N-[4-(2-bromo-acetyl)-phenyl]-methanesulfonamide. The chemical reduction as well as biological reduction of aryl ketone was carried out to obtain a racemate alcohol N [4-(2-bromo-1-hydroxy-ethyl) (4-methanesulfonamide)]ethanol and chiral (S)-N-[4-(2-bromo-1-hydroxy-ethyl)(4- methanesulfonamide)]ethanol, respectively. (S)-N-[-4-(2-bromo-1-hydroxy-ethyl) (4- methanesulfonamide)]ethanol is a key intermediate for the synthesis of (S)-sotalol. The biological reduction was carried out by using whole cells and found that 96 % conversion was obtained at 12th h of reaction after that the percentage conversion decreased.
- Meena, Kamlesh,Ravi
-
experimental part
p. 1316 - 1318
(2012/09/07)
-
- 4-Amino-5-(arylaminomethyl)-2-(methylthio)furo[2,3-d]pyrimidines via Mitsunobu reaction of 4-amino-5-(hydroxymethyl)-2-(methylthio)furo[2,3-d] pyrimidine with N-mesyl- and N-nosylarylamines
-
An efficient method for the synthesis of 4-amino-5-(arylaminomethyl)-2- (methylthio)furo[2,3-d]pyrimidines via the Mitsunobu reaction of 4-amino-5-(hydroxymethyl)-2-(methylthio)furo[2,3-d]pyrimidine with N-mesyl- and N-nosylarylamines, and subsequent removal of the mesyl and nosyl groups, has been developed. The influence of substituents in the arylamine moiety on the Mitsunobu reaction was investigated. An unexpected nucleophilic substitution of a nitro group in the reaction of N-({4-amino-2-(methylsulfonyl)furo[2,3-d] pyrimidin-5-yl}methyl)-4-nitro-N-phenylbenzenesulfonamide with sodium methoxide was observed. Georg Thieme Verlag Stuttgart · New York.
- Masevicius, Viktoras,Petraityte, Grazina,Tumkevicius, Sigitas
-
experimental part
p. 1329 - 1338
(2012/07/01)
-
- Mild Pd-catalyzed N -arylation of methanesulfonamide and related nucleophiles: Avoiding potentially genotoxic reagents and byproducts
-
A convenient, general, and high yielding Pd-catalyzed cross-coupling of methanesulfonamide with aryl bromides and chlorides is reported. The use of this method eliminates concern over genotoxic impurities that can arise when an aniline is reacted with methanesulfonyl chloride. The application of this method to the synthesis of dofetilide is also reported.
- Rosen, Brandon R.,Ruble, J. Craig,Beauchamp, Thomas J.,Navarro, Antonio
-
supporting information; experimental part
p. 2564 - 2567
(2011/06/25)
-
- α-Substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists
-
A series of α-substituted N-(4-tert-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. α-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, Ki = 41 and 39.2 nM and Ki(ant) = 4.5 and 37 nM).
- Chung, Jae-Uk,Kim, Su Yeon,Lim, Ju-Ok,Choi, Hyun-Kyung,Kang, Sang-Uk,Yoon, Hae-Seok,Ryu, HyungChul,Kang, Dong Wook,Lee, Jeewoo,Kang, Bomi,Choi, Sun,Toth, Attila,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Lundberg, Daniel J.,Blumberg, Peter M.
-
p. 6043 - 6053
(2008/03/18)
-
- Synthesis and biological evaluation of methanesulfonamide analogues of rofecoxib: Replacement of methanesulfonyl by methanesulfonamido decreases cyclooxygenase-2 selectivity
-
A new group of 3-(4-substituted-phenyl)-4-(4-methylsulfonamidophenyl)-2(5H)furanones in which the methylsulfonyl (MeSO2) COX-2 pharmacophore present in rofecoxib was replaced by a methanesulfonamido (MeSO2NH) moiety, and where the substituent at the para-position of the C-3 phenyl ring was simultaneously varied (H, F, Cl, Br, Me, OMe), were evaluated to determine the combined effects of steric and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. Structure-activity relationship (SAR) studies showed that compounds having a neutral (H), or electronegative halogen (F, Cl, Br), substituent at the para-position of the C-3 phenyl ring inhibited both COX-1 and COX-2 with COX-2 selectivity indexes in the 3.1-39.4 range. In contrast, compounds having an electron-donating Me or OMe substituent were selective inhibitors of COX-2 (COX-1 IC50 > 100 μM). These SAR data indicate the 3-aryl-4-(4-methylsulfonamidophenyl)-2(5H)furanone scaffold provides a suitable template to design COX inhibitors with variable COX-2 selectivity indexes.
- Zarghi, Afshin,Praveen Rao,Knaus, Edward E.
-
p. 1056 - 1061
(2007/10/03)
-
- Copper-catalyzed cross-coupling of sulfonamides with aryl iodides and bromides facilitated by amino acid ligands
-
A highly general, convenient, and inexpensive catalyst system was developed for the N-arylation of sulfonamides with aryl iodides or bromides by using 5-20 mol % of CuI as catalyst, 20 mol % of N-methylglycine (for aryl iodides) or N,N-dimethylglycine (for aryl bromides) as ligand, and K3PO 4 as base.
- Deng, Wei,Liu, Lei,Zhang, Chen,Liu, Min,Guo, Qing-Xiang
-
p. 7295 - 7298
(2007/10/03)
-
- 4-(METHYL SULFONYL AMINO) PHENYL ANALOGUES AS VANILLOID ANTAGONIST SHOWING EXCELLENT ANALGESIC ACTIVITY AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
-
The present invention relates to novel 4-(methylsulfonylamino) phenyl analogue as a potent vanilloid receptor antagonist and the pharmaceutical compositions comprising the same. The inventive compound can be useful for analgesics to prevent, alleviate or treat pain diseases or inflammatory disease comprising pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease, inflammatory disease and urgent urinary incontinence.
- -
-
-
- Chain-branched 1,3-dibenzylthioureas as vanilloid receptor 1 antagonists
-
A series of chain-branched 1,3-dibenzylthiourea derivatives were synthesized, and tested their antagonist activity against vanilloid receptor 1. Chain-branching led to a significant change in the mode of action and the potency. (R)-Methyl or ethyl-branched 1,3-dibenzylthiourea derivatives showed the most potent antagonist activity up to the IC50 value of 0.05 μM which is 10-fold more potent than capsazepine.
- Ryu, Chong Hyun,Jang, Mi Jung,Jung, Jeong Wha,Park, Ju-Hyun,Choi, Hye Young,Suh, Young-Ger,Oh, Uhtaek,Park, Hyeung-Geun,Lee, Jeewoo,Koh, Hyun-Joo,Mo, Joo-Hyun,Joo, Yung Hyup,Park, Young-Ho,Kim, Hee-Doo
-
p. 1751 - 1755
(2007/10/03)
-
- Novel thiourea derivatives and the pharmaceutical compositions containing the same
-
The present invention relates to novel thiourca derivatives as a modulator for vanilloid receptor (VR) and the phar- maceutical compositions containing the same. As diseases associated with the activity of vanilloid receptor, pain acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflam- matory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases.
- -
-
-
- A convenient reductive deamination (hydrodeamination) of aromatic amines
-
Reductive deamination (hydrodeamination) of aromatic amines can be conveniently carried out by amination of the corresponding arylamine methanesulfonamides using chloroamine under alkaline conditions. The intermediate aryl methanesulfonylhydrazines directly eliminate methanesulfinic acid, affording diazenes which extrude nitrogen affording the desired deaminated products. Both sulfonamide formation and reduction reactions occur in high yield and are compatible with a variety of functional groups.
- Wang,Guziec Jr.
-
p. 8293 - 8296
(2007/10/03)
-
- Antiarrhythmic N-aminoalkylene alkyl and aryl sulfonamides
-
The present invention provides novel sulfonanilide and benzene-alkylaminium compounds which are the products of processes utilizing novel intermediates. Both the novel compounds and the novel intermediates are useful for the therapeutic or prophylactic treatment of arrhythmic activity.
- -
-
-
- Substituent effects in infrared spectroscopy-VII. Meta and para substituted methanesulphonanilides
-
Substituent effects on the NH frequencies of the conformers of methanesulphonanilides, their cyclic dimers and their hydrogen bonded complexes with acetonitrile have been analysed by means of the Hammet equation.An electron-withdrawing substituent may either increase or decrease ν(NH) in the XC6H4NHY series according to the electronic nature of the Y group.This can be explained by the non-monotonic dependence of the NH stretching frequency on the ionic character of the NH bond.
- Laurence, C.,Berthelot, M.,Lucon, M.,Tsuno, Y.
-
p. 791 - 796
(2007/10/02)
-