- Novel synthetic aromatic thiourea derivatives and investigations on their cytotoxic potential efficacy
-
Aromatic thiourea derivatives were synthesized by standard reactions from isothiocyanates in high yield. An efficient one-pot synthesis of primary amine with carbon disulfide involving the intermediate dithiocarbamate conversion using T3P (propane phosphonic anhydride) to isothiocyanate is reported. Newly synthesized compounds showed excellent luminescence property. Cytotoxic investigation with different human cancer cell lines showed IC50 values varying from of 17 to 40 μM for N-phenethyl-3,4-dihydroisoquinoline-2(1H)-carbothioamide (SCR172) among other molecules. Increase in Sub G1 population and increased depolarisation of mitochondria were evident in cells treated with SCR172, suggesting its role as a cancer therapeutic agent. This provides a lead structure for further synthetic modifications.
- Ray, Ujjayinee,John, Franklin,Pooppadi, Sayeesh,George, Jinu,Sharma, Shivangi,Raghavan, Sathees C
-
-
- Synthesis of isothiocyanates using DMT/NMM/TsO? as a new desulfurization reagent
-
Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3 N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO? ) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L-and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.
- Janczewski, ?ukasz,Kolesińska, Beata,Kr?giel, Dorota
-
-
- Synthesis of Multifunctional 2-Aminobenzimidazoles on DNA via Iodine-Promoted Cyclization
-
2-Aminobenzimidazole cores are among the most common structural components in medicinal chemistry and can be found in many biologically active molecules. Herein, we report a mild protocol for the synthesis of multifunctional 2-aminobenzimidazoles on-DNA with broad substrate scopes. The reaction conditions expand our ability to design and synthesize 2-aminobenzimidazole core-focused DNA-encoded libraries.
- Fan, Jing,Feng, Jing,Franklin, G. Joseph,Lancia, David R.,Li, Jin,Liu, Guansai,O'connell, Jonathan,Peng, Ting,Su, Liqiang,Wan, Jinqiao
-
supporting information
(2020/02/13)
-
- Synthesis of thiocarbamoyl fluorides and isothiocyanates using amines with CF3SO2Cl
-
A practical and efficient method to synthesize thiocarbamyl fluorides and isothiocyanates from amines with trifluoromethanesulfonyl chloride was developed. In the presence of the reducing agent triphenylphosphine and sodium iodide, thiocarbamyl fluorides and isothiocyanates were synthesized from secondary/primary amine in moderate to excellent yields, respectively. A broad scope of substrates and good functional group compatibility were observed.
- Jiang, Lvqi,Yi, Wenbin,Wei, Jingjing,Liang, Shuaishuai
-
p. 12374 - 12381
(2020/11/10)
-
- Preparation method of phenethyl isothiocyanate
-
The invention relates to a preparation method of phenethyl isothiocyanate. The preparation method of phenylethyl isothiocyanate takes phenylethylamine and carbon disulfide as raw materials and triethylamine as a base to firstly generate dithiocarbamates, and then uses p-toluenesulfonyl chloride to carry out desulfurization to obtain the phenylethyl isothiocyanate. Compared with the prior art, thesynthesis method uses cheaper raw materials which are easy to transport, has high safety, has relatively mild reaction conditions and high reaction yield, therefore, the method solves the problems oflow conversion rate, low boiling point of desulfurizer, large toxicity, extremely unsafe transportation, high product cost and the like existing in the prior art.
- -
-
Paragraph 0048-0063
(2020/01/25)
-
- HIGH-PURITY ISOTHIOCYANATE COMPOUND PREPARATION METHOD FOR INDUSTRIAL PRODUCTION
-
The present invention provides a high-purity isothiocyanate compound preparation method for industrial production. Specifically, in the method, organic amine and CS2 are used as raw materials to prepare the thiocarbamate, and then desulfurization is carried out, and the high-purity isothiocyanate compound is obtained by using purification, post-processing and other methods. The method in the present invention is suitable for industrial production, is simple in the post-processing, has a high yield rate, and allows the product to have a high purity, and is suitable for the production of the isothiocyanate compound in the pharmaceutical industry.
- -
-
Paragraph 0104-0116
(2020/04/09)
-
- Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
-
In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer.
- Bo-Wang,He, Zhang-Xu,Li, Yi-Han,Liu, Hong-Min,Ma, Li-Ying,Ma, Qin,Tao, Yuan-Yuan,Wang, Hao-Jie,Wu, Hui-Pan,Zhang, Xin-Hui,Zhao, Bing
-
-
- Synthesis and SAR of novel capsazepine analogs with significant anti-cancer effects in multiple cancer types
-
We previously demonstrated that capsazepine (CPZ), a synthetic transient receptor potential Vanilloid subtype 1 (TRPV1) antagonist, has significant anti-cancer effects in vivo. The purpose of this study was to develop more potent analogs based upon CPZ pharmacophore and structure–activity relationships (SAR) across analogs. We generated 30 novel compounds and screened for their anti-proliferative effects in cultured HeLa cervical cancer cells. Cell viability assays identified multiple compounds with IC50s 50 50s of 1–2.5 μM in HSC-3and PC-3cells. Thus, we propose that these novel CPZ analogs may serve as efficacious therapeutic agents against multiple tumor types that warrant further development for clinical application.
- Chapa, Jorge De La,Valdez, Matthew,Ruiz, Franscisco,Gonzales, Keith,Mitchell, Wes,McHardy, Stanton F.,Hart, Matthew,Polusani, Srikanth R.,Gonzales, Cara B.
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p. 208 - 215
(2018/12/11)
-
- Design, synthesis and evaluation of thiourea derivatives as antimicrobial and antiviral agents
-
Background: The development of drug-resistant by bacteria appears rapidly and thus making the effectiveness of antibiotics severely limited. Methods: A series of thiourea derivatives was synthesized, characterized and evaluated for their in vitro antibacterial, antifungal and antiviral activities. Results: Structures of the newly synthesized compounds were confirmed by elemental and spectral analysis. The biological results showed that some of the target compounds displayed comparable antimicrobial and antiviral activities with reference drugs. Structure-activity relationship studies revealed that the ortho-chloro or fluoro substituted phenyl at Ar1 and substituted pyridinyl at Ar2 positions of the thiourea nucleus are essential for their in vitro antimicrobial and anti-HIV activity. In particular, compounds 8 and 10 showed better activity against the tested bacteria, fungi and viral strains than other synthesized PET derivatives reported in the present study. Conclusion: These results provide an encouraging lead that could be used for the development of new potent antiviral and antimicrobial agents.
- Ravichandran, Veerasamy,Shalini, Sivadasan,Kumar, Krishnan Suresh,Rajak, Harish,Agrawal, Ram Kishore
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p. 618 - 624
(2019/06/25)
-
- Organophosphine-free copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur
-
A copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur in the absence of organophosphine has been established. This approach represents a simple and efficient one-pot synthesis of isothiocyanates, and features excellent functional group tolerance and the use of a cheap, safe and odorless sulfur source. Moreover, this process could directly provide isothiocyanate analogous bioactive molecules, thiocarbonyl-containing pesticides and facile construction of benzoxazole and benzimidazole frames.
- Feng, Wei,Zhang, Xing-Guo
-
supporting information
p. 1144 - 1147
(2019/01/28)
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- Isothiocyanate synthesized by three components and preparation method of isothiocyanate
-
The invention discloses isothiocyanate and a preparation method thereof. The method comprises the steps that primary amine, sodium difluorobromoacetate and elemental sulfur are taken as reactants forreaction; the reaction is carried out under the action of a copper catalyst, wherein the copper catalyst is any one of cuprous chloride, copper bromide, cuprous iodide, copper chloride and copper trifluoromethanesulfonate; an alkali is also added, wherein the alkali is any one of sodium bicarbonate, potassium carbonate, cesium carbonate, potassium phosphate, DABCO and sodium tert-butoxide; the whole reaction is carried out in a solvent, wherein the solvent is acetonitrile or dimethyl sulfoxide, the reaction temperature is 80-120 DEG C, and the reaction time is 10-14 hours. The method can directly synthesize the target product, does not need to separate intermediate products and only needs stirring and heating reaction under normal pressure to obtain the target product, and the yield can beup to 87%; a waste solution is fewer during the reaction, and the method protects the environment and ensures the health of an operator; in addition, a series of isothiocyanate derivatives can be prepared, and the method has a stronger substrate universality.
- -
-
Paragraph 0053
(2019/04/26)
-
- Direct, Microwave-Assisted Synthesis of Isothiocyanates
-
A microwave-assisted desulfuration of readily available dithiocarbamates, formed in situ from primary amines, leading to target isothiocyanates has been developed. This efficient protocol provides a rapid, environmentally benign route to aliphatic and aromatic isothiocyanates.
- Janczewski, ?ukasz,Gajda, Anna,Gajda, Tadeusz
-
supporting information
p. 2528 - 2532
(2019/04/03)
-
- Method for jointly preparing isothiocyanate and phosphorus, nitrogen and sulfur flame retardants
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The invention discloses a method for jointly preparing isothiocyanate and phosphorus, nitrogen and sulfur flame retardants. The method comprises the following steps: taking amine and CS2 as raw materials; generating dithiocarbamate by reacting in a solvent under the existence of alkali; reacting with neopentyl glycol phosphoryl chloride, thereby acquiring an isothiocyanate compound (I); acidizingby-product 1,3,2-phosphorus dioxidehexane thiophosphate (II); generating a salt by reacting with melamine in the solvent, thereby acquiring the phosphorus, nitrogen and sulfur flame retardants (III).According to the method provided by the invention, isothiocyanate and phosphorus, nitrogen and sulfur flame retardants can be jointly prepared; operation is simple and convenient; product yield is high; atom is economical; the prepared phosphorus, nitrogen and sulfur flame retardants (III) have an excellent anti-flaming effect.
- -
-
Paragraph 0014
(2019/05/22)
-
- Novel thiosemicarbazone derivatives containing indole fragment as potent and selective anticancer agent
-
Potent and safe anticancer drugs research and development are still on the way to human health. In this report, a series of novel thiosemicarbazone derivatives containing indole fragment were designed and synthesized. Most compounds exhibited excellent antiproliferative activity against PC3, MGC803 and EC109 cell lines with low micromolar IC50 (0.14–12μM). Especially, compound 5j can selectively inhibit PC3 cells in three tested tumor cells with IC50 value of 0.14 μM, which may be attributed to a synergistic effect after introducing indole fragment into the TSC structure. Meanwhile, compound 5j displayed more selectivity in PC3 cells toward two normal WPMY-1 and GES-1 cell lines, compared to those of 3-AP and DPC. We also found that 5j can effectively inhibit PC3 cell proliferation, colonization and induce apoptosis. What's more, 5j may significantly suppress migration and invasion by blocking the EMT process but had no effect on cell cycle. Collectively, our findings indicate that 5j with structure of thiosemicarbazone containing indole may serve as a useful anticancer lead for further optimization and development.
- He, Zhangxu,Qiao, Hui,Yang, Feifei,Zhou, Wenjuan,Gong, Yunpeng,Zhang, Xinhui,Wang, Haojie,Zhao, Bing,Ma, Liying,Liu, Hong-min,Zhao, Wen
-
-
- Na2S2O8-mediated efficient synthesis of isothiocyanates from primary amines in water
-
We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates by the two procedures in satisfactory yields. Halogens, benzylic C-H bonds, methylthio, nitro, ester, alkenyl, electron-rich or -deficient (hetero)aryls, acetylenyl, and even phenolic and alcoholic hydroxyls are well tolerated. The one-pot procedure in water can also be used to realize the preparation of chiral isothiocyanates from chiral amines, and the modification of bioactive structures with free amino groups. In large-scale preparation, simple and practical purification procedures independent of column chromatography are developed.
- Fu, Zhicheng,Yuan, Wenhao,Chen, Ning,Yang, Zhanhui,Xu, Jiaxi
-
supporting information
p. 4484 - 4491
(2018/10/17)
-
- T3P - A Benign Desulfurating Reagent in the Synthesis of Isothiocyanates
-
A number of alkyl, aryl and bifunctional isothiocyanates are obtained in moderate to high yields (41-94%) in a two-step, one-pot reaction of the parent primary amines or their salts with carbon disulfide, followed by reaction of the thus formed dithiocarbamates with T3P (propane phosphonic acid anhydride) as a new and efficient desulfurating agent.
- Janczewski, ?ukasz,Gajda, Anna,Frankowski, Sebastian,Goszczyński, Tomasz M.,Gajda, Tadeusz
-
p. 1141 - 1151
(2017/12/06)
-
- Rational modifications on a benzylidene-acrylohydrazide antiviral scaffold, synthesis and evaluation of bioactivity against Chikungunya virus
-
Chikungunya virus is a re-emerging arbovirus transmitted to humans by Aedes mosquitoes, responsible for an acute febrile illness associated with painful and debilitating arthralgia, which can persist for several months or become chronic. Over the past few years, infection with this virus has spread worldwide with a previously unknown virulence. No specific antiviral treatments nor vaccines are currently available against this important pathogen. Starting from the structure of a class of selective anti-CHIKV agents previously identified in our research group, different modifications to this scaffold were rationally designed, and 69 novel small-molecule derivatives were synthesised and evaluated for their inhibition of Chikungunya virus replication in Vero cells. Further structure-activity relationships associated with this class of antiviral agents were elucidated for the original scaffolds, and novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these new structures as antivirals against Chikungunya virus.
- Giancotti, Gilda,Cancellieri, Michela,Balboni, Andrea,Giustiniano, Mariateresa,Novellino, Ettore,Delang, Leen,Neyts, Johan,Leyssen, Pieter,Brancale, Andrea,Bassetto, Marcella
-
supporting information
p. 56 - 68
(2018/03/06)
-
- Isothiocyanation of amines using the Langlois reagent
-
The Langlois reagent was found to be effective for the isothiocyanation of primary amines in the presence of copper iodide and diethyl phosphonate.
- Liao, Yan-Yan,Deng, Jian-Chao,Ke, Yan-Ping,Zhong, Xiao-Lin,Xu, Li,Tang, Ri-Yuan,Zheng, Wenxu
-
supporting information
p. 6073 - 6076
(2017/07/10)
-
- New mild and simple approach to isothiocyanates: A class of potent anticancer agents
-
In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity against human cancer cell line Panc1 and HGC27 compared with PEITC. Compounds 6 and 7 induced more apoptosis in pancreatic cancer cells but less toxicity in non-cancer cells. Further biological study demonstrated that 7 substantially increased intracellular reactive oxygen species (ROS) and depleted glutathione (GSH), leading to an oxidative stress to kill cancer cell.
- Luo, Bingling,Wang, Jiankang,Li, Xiaobing,Lu, Wenhua,Yang, Jing,Hu, Yumin,Huang, Peng,Wen, Shijun
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-
- The role of 5-arylalkylamino- and 5-piperazino- moieties on the 7-aminopyrazolo[4,3-d]pyrimidine core in affecting adenosine A1 and A2A receptor affinity and selectivity profiles
-
New 7-amino-2-phenylpyrazolo[4,3-d]pyrimidine derivatives, substituted at the 5-position with aryl(alkyl)amino- and 4-substituted-piperazin-1-yl- moieties, were synthesized with the aim of targeting human (h) adenosine A1 and/or A2A receptor subtypes. On the whole, the novel derivatives 1–24 shared scarce or no affinities for the off-target hA2B and hA3 ARs. The 5-(4-hydroxyphenethylamino)- derivative 12 showed both good affinity (Ki = 150 nM) and the best selectivity for the hA2A AR while the 5-benzylamino-substituted 5 displayed the best combined hA2A (Ki = 123 nM) and A1 AR affinity (Ki = 25 nM). The 5-phenethylamino moiety (compound 6) achieved nanomolar affinity (Ki = 11 nM) and good selectivity for the hA1 AR. The 5-(N4-substituted-piperazin-1-yl) derivatives 15–24 bind the hA1 AR subtype with affinities falling in the high nanomolar range. A structure-based molecular modeling study was conducted to rationalize the experimental binding data from a molecular point of view using both molecular docking studies and Interaction Energy Fingerprints (IEFs) analysis. (Figure presented.).
- Squarcialupi, Lucia,Betti, Marco,Catarzi, Daniela,Varano, Flavia,Falsini, Matteo,Ravani, Annalisa,Pasquini, Silvia,Vincenzi, Fabrizio,Salmaso, Veronica,Sturlese, Mattia,Varani, Katia,Moro, Stefano,Colotta, Vittoria
-
p. 248 - 263
(2017/11/10)
-
- Investigations of the Thermal Responsiveness of 1,4,2-Oxathiazoles
-
The first systematic study of the thermal rearrangement/fragmentation of 5,5-disubstituted 1,4,2-oxathiazoles into isothiocyanates is reported. Structure-activity relationships reveal that the choice of substituent at the 5-position of the 1,4,2-oxathiazoles is the predominant factor to influence the ease of fragmentation.
- Hewitt, Russell J.,Ong, Michelle Jui Hsien,Lim, Yi Wee,Burkett, Brendan A.
-
supporting information
p. 6687 - 6700
(2015/10/29)
-
- The Dual Reactivity of 5-S/5-O-Phenyl-1,4,2-oxathiazoles: A Fragmentation Pathway That Affords Nitriles in the Presence of Water
-
The rearrangement of substituted 1,4,2-oxathiazoles to nitriles in the presence of water is described. Preliminary investigations suggest that the reaction pathway proceeds via a 1,4,2-oxathiazolium intermediate, followed by trapping with water and subsequent decomposition to products. An unprecedented rearrangement of 5-phenyl-1,4,2-oxathiazoles bearing a C5 leaving group to nitriles in the presence of water is described.
- Lim, Yi Wee,Hewitt, Russell J.,Burkett, Brendan A.
-
supporting information
p. 4840 - 4842
(2015/08/03)
-
- The synthesis of sulforaphane analogues and their protection effect against cisplatin induced cytotoxicity in kidney cells
-
A series of sulforaphane analogues were synthesized with various amines by treatment of carbon disulfide followed by Boc2O and DMAP. These synthesized sulforaphane analogues were tested on cisplatin treated cultured LLC-PK1 kidney cell line. Among these analogues, several compounds including SF5 show a potent effect on kidney cell protection assay at the concentration of 2.5 μM. Further studies with compound SF5 revealed that the kidney cell protection effect was related by inhibiting the apoptosis pathway through JNK-p53-caspase apoptotic cascade. Compound SF5 may be considered as a promising candidate for the development of new kidney protection agent against drug induced acute kidney disease.
- Kim, Taejung,Kim, Young-Joo,Han, Im-Ho,Lee, Dahae,Ham, Jungyeob,Kang, Ki Sung,Lee, Jae Wook
-
supporting information
p. 62 - 66
(2015/02/19)
-
- Purification-Free, Small-Scale Synthesis of Isothiocyanates by Reagentless Fragmentation of Polymer-Supported 1,4,2-Oxathiazoles
-
The synthesis of isothiocyanates (ITCs) by employing polymer-supported 1,4,2-oxathiazoles is described. The ITCs are obtained in moderate yields and high purity through a reagentless, thermal fragmentation of polymer-supported 1,4,2-oxathiazoles that are obtained by trapping nitrile oxides with polymer-supported thiocarbonates. A purification-free, small-scale synthesis for isothiocyanates (ITCs) is reported that proceeds through a catch-and-release system. This is a convenient method to produce small quantities of ITCs in high purity for screening purposes.
- Burkett, Brendan A.,Fu, Pincheng,Hewitt, Russell J.,Ng, Su Ling,Toh, Joel D. W.
-
p. 1053 - 1058
(2015/10/05)
-
- Purification-free, small-scale synthesis of isothiocyanates by reagentless fragmentation of polymer-supported 1,4,2-oxathiazoles
-
The synthesis of isothiocyanates (ITCs) by employing polymer-supported 1,4,2-oxathiazoles is described. The ITCs are obtained in moderate yields and high purity through a reagentless, thermal fragmentation of polymer-supported 1,4,2-oxathiazoles that are obtained by trapping nitrile oxides with polymer-supported thiocarbonates. A purification-free, small-scale synthesis for isothiocyanates (ITCs) is reported that proceeds through a catch-and-release system. This is a convenient method to produce small quantities of ITCs in high purity for screening purposes. Copyright
- Burkett, Brendan A.,Fu, Pincheng,Hewitt, Russell J.,Ng, Su Ling,Toh, Joel D. W.
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p. 1053 - 1058
(2014/03/21)
-
- Aggrecanase-2 inhibitors based on the acylthiosemicarbazide zinc-binding group
-
Osteoarthritis is a disabling disease characterized by the articular cartilage breakdown. Aggrecanases are potential therapeutic targets for the treatment of this pathology. At the starting point of this project, an acylthiosemicarbazide was discovered to inhibit aggrecanase-2. The acylthiosemicarbazide Zn binding group is also a convenient linker for library synthesis. A focused library of 920 analogs was thus prepared and screened to establish structure-activity relationships. The modification of the acylthiosemicarbazide was also explored. This strategy combining library design and discrete compounds synthesis yielded inhibitor 35, that is highly selective for aggrecanases over a panel of metalloproteases and inhibits the degradation of native fully glycosylated aggrecan. A docking study generated binding conformations explaining the structure-activity relationships.
- Maingot, Lucie,Elbakali, Jamal,Dumont, Julie,Bosc, Damien,Cousaert, Nicolas,Urban, Agathe,Deglane, Gaelle,Villoutreix, Bruno,Nagase, Hideaki,Sperandio, Olivier,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
-
p. 244 - 261
(2013/10/01)
-
- ISOTHIOCYNATES AND GLUCOSINOLATE COMPOUNDS AND ANTI-TUMOR COMPOSITIONS CONTAINING SAME
-
The present invention provides glucosinolate and isothiocyanate compounds and related methods for synthesizing these compounds and analogs. In certain embodiments, these glucosinolate and isothiocyanate compounds are useful and chemopreventive and or chemotherapeutic agents.
- -
-
Paragraph 0094; 0096; 0119
(2013/05/21)
-
- Selectfluor F-TEDA-BF4 mediated thiocyanation or isothiocyanation of alcohols by in situ generation of [+SCN] under heterogeneous and neutral conditions
-
A convenient approach for thiocyanation of alcohols has been developed using ammonium thiocyanate as thiocyanating agent in the presence of a catalytic amount of Selectfluor F-TEDA-BF4 in aqueous acetonitrile. In this method various alcohols generally afforded the corresponding thiocyanates or isothiocyanates directly in good to high yield under heterogeneous and neutral conditions.
- Khazaei, Ardeshir,Rahmati, Sadegh,Khalafi-Nezhad, Ali,Saednia, Shahnaz
-
experimental part
p. 123 - 125
(2012/05/05)
-
- Structure-activity relationships (SAR) research of thiourea derivatives as dual inhibitors targeting both HIV-1 capsid and human cyclophilin A
-
HIV-1 capsid (CA) and human cyclophilin A (CypA) play important roles in HIV-1 assembly and disassembly processes, which are critical in HIV-1 replication. Based on the discovery of thiourea derivatives targeting both of the two proteins and indicating effective inhibitory activities in our group, we designed and synthesized a new class of thiourea derivatives. Their abilities to bind to capsid and cyclophilin A were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity, and PPIase inhibition assay. Furthermore, the newly synthesized compounds were tested for their antiviral activities and cytotoxicities using CEM cells. According to the biological evaluation and subsequent molecular docking analyses, we studied the structure-activity relationships of thiourea derivatives. Three optimal compounds (K17, K24, K25) based on the achieved structure-activity relationships would be the basis for future optimization.
- Chen, Kan,Tan, Zhiwu,He, Meizi,Li, Jiebo,Tang, Shixing,Hewlett, Indira,Yu, Fei,Jin, Yinxue,Yang, Ming
-
scheme or table
p. 25 - 33
(2011/04/17)
-
- Use of Isothiocyanates Compounds in Treating Prostatic Diseases and Skin Cancer
-
A method for preventing and treating prostatic diseases and skin cancer using naturally or artificially synthesized isothiocyanates compounds or the derivatives or metabolites thereof.
- -
-
-
- SAR studies of capsazepinoid bronchodilators 3: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region)
-
Certain derivatives and analogues of capsazepine are potent in vitro inhibitors of bronchoconstriction in human small airways. During an investigation of the dependency of the potency on the structural features of the capsazepinoids in the thiourea moiety (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region), it was revealed that capsazepinoids with a thiourea or an amide link between the B-ring and the C-region in general have a good bronchorelaxing activity, while urea is a less attractive choice. Further, it was shown that 1,2,3,4-tetrahydroisoquinolines with a 2-(phenyl)ethyl derivative as the C-region are considerably more potent than those with an octyl group, while 2,3,4,5-tetrahydro-1H-2-benzazepines were found to be more insensitive to the nature of the C-region.
- Berglund, Magnus,Dalence-Guzman, Maria F.,Skogvall, Staffan,Sterner, Olov
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p. 2529 - 2540
(2008/09/21)
-
- ISOTHIOCYANATES AND GLUCOSINOLATE COMPOUNDS AND ANTI-TUMOR COMPOSITIOS CONTAINING SAME
-
The present invention provides glucosinolate and isothiocyante compounds and related methods for synthesizing these compounds and analogs. In certain embodiments, these glucosinolate and isothiocyanate compounds are useful and chemopreventive and or chemotherapeutic agents.
- -
-
Page/Page column 35
(2008/06/13)
-
- Synthesis and anticancer activity comparison of phenylalkyl isoselenocyanates with corresponding naturally occurring and synthetic isothiocyanates
-
Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure - activity relationship comparison of ISCs with ITCs and effect of the increasing alkyl chain length in inhibiting cancer cell growth were evaluated on melanoma, prostate, breast, glioblastoma, sarcoma, and colon cancer cell lines. IC50 values for ISC compounds were generally lower than their corresponding ITC analogues. Similarly, in UACC 903 human melanoma cells, the inhibition of cell proliferation and induction of apoptosis were more pronounced with ISCs compared to ITCs. Further, ISCs and ITCs effectively inhibited melanoma tumor growth in mice following intraperitoneal xenograft. A similar reduction in tumor size was observed at 3 times lower doses of ISCs compared to corresponding ITCs.
- Sharma, Arun K.,Sharma, Arati,Desai, Dhimant,Madhunapantula, SubbaRao V.,Sung, Jin Huh,Robertson, Gavin P.,Amin, Shantu
-
scheme or table
p. 7820 - 7826
(2009/12/07)
-
- Substituted urea/thiourea derived from fluoxetine as potent appetite suppressants
-
A series of urea and thiourea analogues of fluoxetine (5-17) were synthesized and evaluated for their anorexigenic and antidepressant activities. The related conformationally restrained analogues (20-23) were also prepared for structure-activity relationship (SAR) studies. Many of these derivatives (5, 6, 8, 10, 12, 13, 16, and 23) exhibited significant anorexigenic activity and interestingly were devoid of antidepressant activity, thus emerging as a promising tool for further research work.
- Bhandari, Kalpana,Srinivas, Nagarapu,Sharma, Lata,Srivastava, Shipra,Nath, Amar,Nath, Chandishwar
-
p. 103 - 113
(2008/12/22)
-
- Bronchorelaxing compounds
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A compound of the general formula (I) including its pharmaceutically acceptable acid addition salts wherein A is CHR9, wherein R9 is H, C1-C6 alkyl; n is 1-3; B is CHR10, wherein R10 is H, C1-C6 alkyl; m is 1 or 2; D is O or S or optionally NR16, wherein R16 is H, C1-C6 alkyl or C2-C6 acyl; E is CR11R12 or NR13, wherein R11 and R12 are, independent of each other, H or C1-C6 alkyl, R13 is H or C1-C6 alkyl; F is C1-C18 alkyl which may be mono- or di-unsaturated and/or substituted, is useful in treating and preventing pulmonary disease characterized by bronchoconstriction. Also disclosed are pharmaceutical compositions comprising the compound and methods for their manufacture.
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Page/Page column 16
(2010/02/13)
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- A one-pot preparation of isothiocyanates from amines using two phosgene substitutes: bis-(trichloromethyl) carbonate and trichloromethyl chloroformates
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A series of isothiocyanates have been prepared in high yields in a one-pot reaction from commercial amines and carbon disulfide under mild conditions using bis(trichloromethyl)carbonate (BTC) and trichloromethyl chloroformate (TCF) as reagents in the presence of base.
- Bian, Gaofeng,Shan, Weiguang,Su, Weike
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p. 585 - 586
(2007/10/03)
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- Decomposition rates of isothiocyanate conjugates determine their activity as inhibitors of cytochrome P450 enzymes
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Thiol conjugates of isothiocyanates (thiol-ITCs) are metabolites of ITCs formed in the mercapturic acid pathway in mammals. They are effective chemopreventive agents in mouse lung tumor bioassays and in other models. Thiol-ITCs are inhibitors of P450s, but it has not been determined if P450 inhibition is due to conjugates themselves or to parent ITCs released by deconjugation reactions. In studies of mechanism of chemopreventive action of thiol-ITCs, rates of deconjugation of Cys, GSH, and N-acetyl-L-cysteine (NAC) conjugates of benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), 6-phenylhexyl isothiocyanate (PHI-TC), and sulforaphane (SFN), expressed as the first-order rate constant k1 and the half-life of decomposition Dt1/2, were measured in aqueous solutions at pH 7.4 and 37°. The Dt1/2s for the Cys conjugates were severalfold shorter than the Dt1/2s for respective GSH conjugates, while the Dt1/2s for the NAC conjugates were the longest. Cleavage of thiol conjugates was pH dependent, much slower under acidic conditions than at pH 7.4. Inhibition of P450 enzymes by thiol-ITCs was followed using PROD (pentoxyresorufin O-dealkylation) for P450 2B1 and EROD (ethoxyresorufin O-dealkylation) for P450 1A1. The inhibition of PROD and EROD by aqueous thiol-ITCs increased with preincubation time and was roughly parallel to the extent of decomposition of the conjugate that had occurred, indicating that both potency of the respective parent ITC and the rate of reductive cleavage of the conjugate influenced enzyme inhibition. In the presence of 250-1000 μM GSH, comparable to physiological levels, rates of deconjugation of thiol-ITCs were markedly reduced; inhibition of PROD was also proportionately reduced. Slow rates of decomposition of thiol-ITCs anticipated in plasma and tissues suggests that inhibition of P450 enzymes involved in carcinogen activation by ITCs released from thiol-ITCs may not be a principal mechanism for their tumor inhibitory activity; other mechanisms probably contribute to their chemopreventive activity.
- Conaway,Krzeminski,Amin,Chung
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p. 1170 - 1176
(2007/10/03)
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- 2-Chloro-1,3-dimethylimidazolinium chloride. 1. A powerful dehydrating equivalent to DCC
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2-Chloro-1,3-dimethylimidazolinium chloride (DMC) (3) can act as a powerful dehydrating agent, replacing DCC (1) under nearly neutral conditions. Its application to acylation and dehydration is described.
- Isobe, Toshio,Ishikawa, Tsutomu
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p. 6984 - 6988
(2007/10/03)
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- Synthesis and Octopaminergic Agonist Activity of 2-(Substituted benzylamino)-2-thiazolines
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2-(Substituted benzylamino)-2-thiazolines (SBAT) were synthesized by a hydrochloric acid-catalyzed cyclization of the corresponding thioureas, using a reaction of 2-methylthio-2-thiazoline with substituted benzylamines or by alkylating 2-amino-2-thiazoline. 2-(Alkylthio)-2-thiazolines were obtained by alkylating 2-mercaptothiazoline.Most of the SBAT compounds activated adenylate cyclase in homogenates of cockroach ventral nerve cords; the effect of introducing substituents at the phenyl of the SBAT compounds on octopaminergic agonist activity was not significant. 2--2-thiazolines and 2-(alkylthio)-2-thiazolines were not significant octopaminergic agonists.Washing removed nearly all of the activity of one of the SBAT compounds, suggesting that the SBAT compounds bound reversibly to the octopaminergic receptor.
- Hirashima, Akinori,Yoshii, Yutaka,Eto, Morifusa
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p. 1062 - 1065
(2007/10/02)
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- Aminothiazines et aminothiazoles analogues ouverts du levamisole: synthese et approche du mode d'action nematicide
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New compounds with thiazoline or dihydrothiazine rings substituted by alkylamino or arylamino groups were synthesized and screened in vitro against three Nematodes.Inhibition of fumarate-reductase activity was also evaluated.For all in vitro anti-parasitic tests, dihydrothiazines were more potent than corresponding thiazolines derivatives, however, thiazolines showed a greater inhibition of fumarate-reductase.
- Caujolle, Raymond,Amarouch, Hamid,Payard, Marc,Loiseau, Philippe R.,Bories, Christian,et al.
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p. 287 - 292
(2007/10/02)
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- 1,3-Thiazines, XV: New Synthetic Route to N-Substituted Tetrahydro-1,3-thiazine-2-thiones
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A new synthetic route to N-substituted tetrahydro-1,3-thiazine-2-thiones 5 giving good yields for N-aryl compounds is reported.It consists of carbon disulfide cleavage of N,N'-disubstituted 2-iminotetrahydro-1,3-thiazines 3 which leads to 5 and the isothiocyanates 6.
- Hanefeld, Wolfgang,Bercin, Erdogan
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p. 413 - 419
(2007/10/02)
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- THERMAL DEGRADATION OF GLUCOSINOLATES
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Three glucosinolates (allyl-, benzyl- and 2-phenethyl-) were shown to degrade thermally in a GC column to yield products identical with those obtained conventionally on enzymic decomposition, namely nitriles and isothiocyanates.Nitriles were formed more readily at 125 deg but the facility for isothiocyanate production varied slightly with the glucosinolate; 2-phenethylglucosinolate was the most labile of those studied yielding isothiocyanate at a column temperature of 150 deg.Temperature was confirmed as the cause of degradation by isolated heated-tube experiments.The results have significance both with regard to analytical methodology for glucosinolates and their products, and with regard to furthering understanding of the mechanisms of glucosinolate degradation.Key Word Index- Criciferae; glucosinolates; nitriles; isothiocyanates; thermal degradation.
- Macleod, Alexander J.,Panesar, Satwinder S.,Gil, Victor
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p. 977 - 980
(2007/10/02)
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- Nitrogen heterocyclic carboximidamide compounds
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5-, 6- or 7-Membered fully saturated 1-azacarbocyclic-2-ylidene derivatives of guanidine having anti-secretory and hypoglycemic activities, and further useful for treatment of cardiovascular disease states.
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