cas 622-58-2, p-Tolyl isocyanate | Articles data

Articles about 622-58-2Total 98 be found

Article title
Article abstract
Author
Journal number and time
Download

Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer
Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.
Akwii, Racheal,Alvina, Karina,Ashraf-Uz-Zaman, Md,Farshbaf, Mohammad Jodeiri,German, Nadezhda A.,Kallem, Raja Reddy,Mikelis, Constantinos M.,Putnam, William,Sajib, Md Sanaullah,Shahi, Sadisna,Trippier, Paul C.,Wang, Wei,Zhang, Ruiwen
(2020/10/12)

Insecticidal sterilization composition and application thereof
The insecticidal sterilization composition comprises the following raw materials in parts by weight 1 - 50% parts of isopyrazam, 1 - 40% parts of trichloroisocyanuric acid, 1 - 2% parts of synergist and the balance of excipients. By compounding isothiopham and trichloroisocyanuric acid, the effects are complementary, the bactericidal spectrum is wider, and the bactericidal activity is high. Under the action of the initiator A I BN, the intermediate 5, the intermediate 6 and the acrylamide are polymerized to obtain a synergist which is a water-soluble compound and is grafted with a hindered amine structure, a benzophenone structure and a benzisothiazolinone structure.
-
Paragraph 0011-0012; 0041; 0043; 0049; 0051; 0057; 0059

(2021/11/03)

Practical one-pot amidation of N -Alloc-, N -Boc-, and N -Cbz protected amines under mild conditions
A facile one-pot synthesis of amides from N-Alloc-, N-Boc-, and N-Cbz-protected amines has been described. The reactions involve the use of isocyanate intermediates, which are generated in situ in the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, to react with Grignard reagents to produce the corresponding amides. Using this reaction protocol, a variety of N-Alloc-, N-Boc-, and N-Cbz-protected aliphatic amines and aryl amines were efficiently converted to amides with high yields. This method is highly effective for the synthesis of amides and offers a promising approach for facile amidation.
Hong, Wan Pyo,Tran, Van Hieu,Kim, Hee-Kwon
p. 15890 - 15895
(2021/05/19)

Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus
Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78–22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization.
Ruan, Banfeng,Zhang, Yuezhou,Tadesse, Solomon,Preston, Sarah,Taki, Aya C.,Jabbar, Abdul,Hofmann, Andreas,Jiao, Yaqing,Garcia-Bustos, Jose,Harjani, Jitendra,Le, Thuy Giang,Varghese, Swapna,Teguh, Silvia,Xie, Yiyue,Odiba, Jephthah,Hu, Min,Gasser, Robin B.,Baell, Jonathan
supporting information

(2020/02/04)

Design, synthesis and antitumor assessment of phenylureas bearing 5-fluoroindolin-2-one moiety
Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative abil-ity was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of1 H and13 C NMR as well as HR-MS. Three sets of compounds (1a?1c, 2a?2c, and 3a?3c) were ini-tially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a?1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d?1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cyto-toxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF-7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structure-activity studies showed that 1g was the most bioactive antitumor agent among all tested com-pounds, hence a potentially promising lead compound once given further optimization.
Cai, Yunrui,Chen, Tong,Zhu, Huajian,Zou, Hongbin
p. 958 - 968
(2020/08/19)

Discovery of BMS-986235/LAR-1219: A Potent Formyl Peptide Receptor 2 (FPR2) Selective Agonist for the Prevention of Heart Failure
Formyl peptide receptor 2 (FPR2) agonists can stimulate resolution of inflammation and may have utility for treatment of diseases caused by chronic inflammation, including heart failure. We report the discovery of a potent and selective FPR2 agonist and its evaluation in a mouse heart failure model. A simple linear urea with moderate agonist activity served as the starting point for optimization. Introduction of a pyrrolidinone core accessed a rigid conformation that produced potent FPR2 and FPR1 agonists. Optimization of lactam substituents led to the discovery of the FPR2 selective agonist 13c, BMS-986235/LAR-1219. In cellular assays 13c inhibited neutrophil chemotaxis and stimulated macrophage phagocytosis, key end points to promote resolution of inflammation. Cardiac structure and functional improvements were observed in a mouse heart failure model following treatment with BMS-986235/LAR-1219.
Asahina, Yoshikazu,Wurtz, Nicholas R.,Arakawa, Kazuto,Carson, Nancy,Fujii, Kiyoshi,Fukuchi, Kazunori,Garcia, Ricardo,Hsu, Mei-Yin,Ishiyama, Junichi,Ito, Bruce,Kick, Ellen,Lupisella, John,Matsushima, Shingo,Ohata, Kohei,Ostrowski, Jacek,Saito, Yoshifumi,Tsuda, Kosuke,Villarreal, Francisco,Yamada, Hitomi,Yamaoka, Toshikazu,Wexler, Ruth,Gordon, David,Kohno, Yasushi
supporting information
p. 9003 - 9019
(2020/10/18)

Sulfonylurea dehydroabietate compound and preparation method and application thereof
The invention discloses a sulfonylurea dehydroabietate compound and a preparation method and application thereof. The compound has a chemical structural formula represented by a formula shown in the description, wherein R1 is 2-Br, 3-Br, 4-Br, 4-OCH3, 4-F, 2-CH3, 3-CH3, 4-CH3, 2-Cl, 3-Cl or H, and 2, 3 and 4 represent 2, 3 and 4 substituent sites on a benzene ring. The preparation method of the compound comprises the following steps synthesizing sulfonyl chloride dehydroabietate; synthesizing sulfonamide dehydroabietate; synthesizing substituted phenyl isocyanate; synthesizing N'-substituted phenyl-12-sulfonylurea dehydroabietate. The compound disclosed by the invention has better activity and low toxicity and provides a better lead compound for developing antitumor drugs.
-
Paragraph 0106; 0108; 0112

(2019/02/04)

Isothiazolinone compound and corresponding application
The invention provides an isothiazolinone compound with an IDO inhibitory activity, and a preparing method and pharmaceutical application thereof. The invention particularly relates to a compound shown in a formula I, pharmaceutically acceptable salts thereof, isomers and prodrugs, wherein definitions of all groups are shown in the description. The invention further relates to compound drug preparations, drug compositions and the application of the compound drug preparations and the drug compositions in treating, relieving and/or preventing various relevant diseases caused by immunosuppressionsuch as tumors, virus infection or autoimmune diseases. The isothiazolinone compound has the excellent IDO inhibitory activity.
-
Paragraph 0034-0037

(2019/07/08)

One stone two birds: Cobalt-catalyzed in situ generation of isocyanates and benzyl alcohols for the synthesis of N-aryl carbamates
An efficient method for the synthesis of N-aryl carbamates from N-Boc-protected amines has been developed. The cobalt-catalyzed in situ generation of isocyanates from N-Boc-protected amines and benzyl alcohols from benzyl formates has been achieved for the first time, which in turn furnished the corresponding benzyl carbamates in moderate to high yields. The reaction was catalyzed by CoI2 with tris-(4-dimethylaminophenyl)-phosphine as the ligand and zinc powder as the reductant. The developed reaction conditions were found to be compatible for aromatic amines with both electron-donating and -withdrawing substituents.
Li, Sida,Khan, Ruhima,Zhang, Xia,Yang, Yong,Wang, Zheting,Zhan, Yong,Dai, Yuze,Liu, Yue-E,Fan, Baomin
supporting information
p. 5891 - 5896
(2019/06/24)

Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based diaryl urea derivatives for suppressing VEGFR-2 signaling
A novel structural series of tetrahydroisoquinoline-based compounds that incorporate the diaryl urea moiety was designed, synthesized, and biologically evaluated as suppressors of VEFGR-2 signaling. As a consequence, compounds 9k and 9s exhibited comparable or superior cytotoxic activity to that of gefitinib against the tested three cell lines, including A549, MCF-7, and PC-3. Importantly, both of them downregulated the expression of VEGFR-2, and inhibited VEGFR-2 phosphorylation at the concentration of 0.5 or 1.0 μmol/l. Besides, they suppressed human umbilical vein endothelial cell tube formation at the concentration of 4.0 μmol/l. Considering their capability of down-regulating VEGFR-2 expression and inhibiting VEGFR-2 phosphorylation, 9k and 9s may serve as suppressors of angiogenesis for further investigation.
Huang, Yuanzheng,Zhang, Yang,Li, Jiaming,Ma, Xiaodong,Hu, Mengqi,Yang, Yu,Gao, Sufan
p. 508 - 516
(2019/05/14)

Fluoride-Catalyzed Deblocking: A Route to Polymeric Urethanes
We report a fluoride-catalyzed deblocking of urethanes as “blocked” isocyanates. Organic and inorganic sources of fluoride ion proved effective for deblocking urethanes and for converting polyurethanes to small molecules. Distinct from conventional deblocking chemistry involving organometallic compounds and high temperatures, the method we describe is metal-free and operates at or slightly above room temperature. The use of fluorescent blocking agents enabled visual and spectroscopic monitoring of blocking/deblocking reactions, and the selected conditions proved applicable to urethanes containing a variety of blocking groups. The method additionally enabled a one pot deblocking and polymerization with α,ω-diols. Overall, this deblocking/polymerization strategy offers a convenient and efficient solution to problems that have limited the breadth of applications of polyurethane chemistry.
Sheri, Madhu,Choudhary, Umesh,Grandhee, Sunitha,Emrick, Todd
supporting information
p. 4599 - 4602
(2018/03/28)

Decarboxylative Organocatalytic Allylic Amination of Morita–Baylis–Hillman Carbamates
The present study reports the organocatalytic enantioselective allylic amination of Morita–Baylis–Hillman carbamates efficiently catalyzed by a chiral amine in the presence of a Br?nsted acid. Chiral allylic amines were produced in high yields (up to 98 %) and enantioselectivities (up to 97 % ee). This method provides an efficient and easily performed route to prepare α-methylene-β-lactams, and other optically active β-lactams, such as the cholesterol-lowering drug Ezetimibe.
Do?ekal, Vojtěch,?imek, Michal,Dra?ínsky, Martin,Vesely, Jan
supporting information
p. 13441 - 13445
(2018/09/21)

2-[2-(2-methoxyl phenoxyl) ethylamino]-3-aryl-4-quinazolinones compound and application thereof
The invention belongs to the technical field of medicines, and relates to a 2-[2-(2-methoxyl phenoxyl) ethylamino]-3-aryl-4-quinazolinones derivative and application thereof. The 2-[2-(2-methoxyl phenoxyl) ethylamino]-3-aryl-4-quinazolinones derivative comprises a stereisomer of the compound and pharmacologically applicable salt. The general structural formula is as follows: as shown in the description, wherein R is as described in claims and the description. The 2-[2-(2-methoxyl phenoxyl) ethylamino]-3-aryl-4-quinazolinones derivative and salt formed by addition of a pharmacologically applicable acid of the compound can be combined with an existing medicine or used independently to form an influenza virus inhibitor which is used for treating influenza and particularly has a relatively curative effect on various types of influenza A.
-
Paragraph 0047; 0051

(2018/03/25)

2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and application thereof
The invention belongs to the technical field of medicines and relates to 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and an application thereof. 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives comprise stereisomers and pharmaceutically applicable salts of the compounds and have the general structural formula shown in the description, wherein R is described inthe claims and description. The 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives and pharmaceutically applicable acid-added salts of the compounds can be combined with existing medicines or used separately to serve as influenza virus inhibitors to treat influenza and have better curative effects on various type-A influenza in particular.
-
Paragraph 0040; 0049

(2018/04/21)

Synthesis and nematicidal activity of piperazinedione derivatives based on the natural product Barettin
Nematodes are serious constraints of crop production worldwide. However, the traditional nematicides suffer from the side-effects, including environmental and human toxicity. Herein, more than 70 novel piperazinedione derivatives based on the natural product Barettin were synthesized and evaluated against the root-knot nematode Meloidogyne incognita (M. incognita). While most of synthesized compounds exhibited certain nematicidal activity at high concentration, the best one showed a nematicidal activity of 75% at 2.4 μmol/L.
Sun, Haiyang,Li, Hui,Wang, Jiayi,Song, Gonghua
p. 977 - 980
(2017/11/16)

Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase
Inspired by that the multi-target inhibitors against receptor tyrosine kinases (RTKs) have significantly improved the effect of clinical treatment for cancer, and based on the chemical structure of Linifanib (ABT-869, Abbott), two series of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure were designed and synthesized as multi-target inhibitors against RTKs. The preliminary biological evaluation showed that several compounds exhibited comparable potency with Linifanib. Compound S21 was identified as the most potent inhibitor against Fms-like tyrosine kinase 3 (FLT-3), kinase insert domain containing receptor (KDR) and platelet-derived growth factor receptor β (PDGFR-β) with its IC50 values were 4 nM, 3 nM and 8 nM respectively, it also showed potent inhibitory activities against several cancer cells.
Shi, Zhi-Hao,Liu, Feng-Tao,Tian, Hao-Zhong,Zhang, Yan-Min,Li, Nian-Guang,Lu, Tao
p. 4735 - 4744
(2018/08/21)

Phenylquinoline transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of 1-(2-phenylquinoline-4-carbonyl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide
Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a phenylquinoline platform that evolved from Cinchophen lead. This design composes three sections: a phenylquinoline headgroup attached to an aliphatic carboxamides, which is tethered at a phenyl tail group. Optimization of this design led to the identification of 37, comprising a pyrrolidine linker and a trifluoromethyl–phenyl tail. In the TRPV1 functional assay, using cells expressed hTRPV1, 37 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 10.2 nM. In the complete mice analgesic model, 37 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that 37 could be considered as a lead candidate for the further development of antinociceptive drugs.
Liao, Chen,Liu, Yan,Liu, Chunxia,Zhou, Jiaqi,Li, Huilan,Wang, Nasi,Li, Jieming,Liu, Taiyu,Ghaleb, Hesham,Huang, Wenlong,Qian, Hai
p. 845 - 854
(2018/01/10)

Synthesis for novel doramectin derivate and insecticide application thereof
The invention relates to the field of chemistry and chemical engineering and pesticides and aims to provide a novel doramectin derivate, a synthesis method and an insecticide application thereof. According to the technical scheme, the chemical formula of the novel doramectin derivate is shown in the specification, wherein R is one of saturated alkyl, unsaturated alkyl, aryl and heterocyclic aryl; the saturated alkyl is C1-C12 straight chain and branch alkyl; the unsaturated alkyl is C1-C12 straight chain and branch olefin, alkyne or C3-C6 cyclic alkyl; the aryl is monocyclic aromatic group or condensed cyclic aromatic group; and the heterocyclic aryl is one of pyrryl, pyridyl, imidazole, thiazolyl, indolyl, pyrazolyl and quinoline. The doramectin derivate prepared according to the method provided by the invention, compared with the traditional chemical pesticide, has the advantages of high efficiency, low toxicity, environmental protection, and the like, and is expected to become a new generation of green and environment-friendly biopesticide.
-
Paragraph 0132; 0133

(2018/03/24)

3, 4, 5-tri-substituted oxazolidinone compounds and its preparation method (by machine translation)
The invention discloses a formula (I) of the structure shown in the 3, 4, 5? Tri-substituted oxazolidinone compound preparation method, the preparation method comprises: in the organic solvent, like type compound of the structure shown in the (II), of the structure shown in the formula (III) compound, organic base and the contact reaction mixture CuI, wherein R1 is selected from H, C1? C6 alkyl or nitro, R2 is selected from H or C1? C6 alkyl, R3 is selected from H, C1? C10 alkyl or vinyl. The steps of the preparation method is simple, is easy to obtain raw materials and catalyst, mild reaction conditions and high yield, (by machine translation)
-
Paragraph 0051-0053

(2017/04/05)

With anti-tumor effect of a quinazoline-urea derivative and its application (by machine translation)
The present invention relates to a of the general formula (II) anti-tumor function of said quinazoline-urea derivative and its application. The definition of the substituent in the general formula (II) in the specification. This invention, in order to SUO draw non-Buddhist nun and Geftinat compounds as the precursor, retention of SUO draw non-Buddhist nun the pharmocology-carbamido; at the same time, such as in reserved [...] EGFR-TKIs Geftinat, synthesis, and obtain a series of quinazoline-urea derivatives, by the in vitro activity tests, some compounds exhibit excellent anti-tumor activity, such derivatives have high research and utility value. (II). (by machine translation)
-
Paragraph 0139-0142; 0147

(2016/11/02)

Synthesis and antibacterial activity of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N,12-O-cyclic carbamate derivatives
A series of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N,12-O-cyclic carbamate derivatives (6a-h) were designed, synthesized and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against two groups of pathogens of Methicillin-sensitive Staphylococcus aureus (MIC 50 =0.031-2 μg ml -1) except 6g and Methicillin-sensitive S. epidermidis (MIC 50 =0.031-0.5 μg ml -1). MIC 90 of 6d against Methicillin-resistant S. epidermidis was at least 16-fold better than that of erythromycin (EMA), azithromycin (AZM) and ABT-773. 6d and 6e had more potent antibacterial activity against S. pneumoniae than EMA, AZM and ABT-773. In particular, compounds 6d and 6e also showed relatively potent activity against Haemophilus influenzae and Streptococcus hemolyticus.
Zheng, Zhonghui,Du, Deping,Cao, Lili,Liu, Jun,Chen, Xiaofang
p. 811 - 817
(2016/12/07)

Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents
Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure-activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization.
Chen, Jia-Nian,Wang, Xian-Fu,Li, Ting,Wu, De-Wen,Fu, Xiao-Bo,Zhang, Guang-Ji,Shen, Xing-Can,Wang, Heng-Shan
p. 12 - 25
(2015/11/17)

Azabicyalo derivative as well as preparation and application thereof
The invention relates to an azabicyalo derivative as well as preparation and application thereof, and particularly discloses a compound with a structure shown in to the formula (A) or salt thereof acceptable in agricultural pharmacology. The compound in the formula (A) is described in the description in detail, and has an excellent killing effect on nematode.
-
Paragraph 0171; 0172; 0173

(2016/10/07)

Synthesis and characterization of peracetylated S-maltosyl 2-isothiobiurets and 2,4-isodithiobiurets and their in vitro antimicrobial activity
A series of S-hepta-O-acetyl-maltosyl-1-aryl-5-p-tolyl-2-isothiobiurets, S-hepta-O-acetyl-maltosyl-1-aryl-5-p-chloro-phenyl-2-isothiobiurets and S-hepta-O-acetyl maltosyl-1-aryl-5-p-tolyl-2,4-isodithiobiurets have been synthesized by the interaction of various S-hepta-O-acetyl maltosyl-1-aryl isothiocarbamides with p-tolyl isocyanate, p-chloro-phenyl isocyanate and p-tolyl isothiocyanate respectively. The required maltosyl arylisothiocarbamides are synthesized by the displacement of anomeric bromide of acetobromomaltose with aryl thiocarbamides. The identities of these newly synthesized thiomaltosides have been established on the basis of chemical transformations and IR, mass, 1H and 13C NMR spectral studies. These compounds have been screened for their antibacterial and antifungal activities against E. coli, S. aureus, Ps. aeruginosa, S. typhi, R. oligosporus and A. niger. These compounds show most promising activity towards these microorganisms.
Zade, Varsha S.,Deshmukh, Shirish P.
p. 815 - 820
(2015/06/30)

Rhenium-catalyzed C-H aminocarbonylation of azobenzenes with isocyanates
The first C-H aminocarbonylation of azobenzenes with isocyanates is achieved by using rhenium-catalysis, which provides an expedient and atom-economical access to varied o-azobenzamides from readily available starting materials. The reaction efficiency can be enhanced by the catalytic use of sodium acetate via accelerated C-H bond activation.
Geng, Xiaoyu,Wang, Congyang
supporting information
p. 7619 - 7623
(2015/07/15)

Synthesis and pharmacological evaluation of novel triazolo [4, 3-a] tetrahydrobenzo (b) thieno [3, 2-e] pyrimidine-5(4H)-ones
Triazolo[4,3-a]tetrahydrobenzo(b)thieno[3,2-e]pyrimidine-5(4H)-ones (5a-m) were synthesized and characterized by spectral analysis. All 13 derivatives were evaluated for central nervous system (CNS) depressant and skeletal muscle relaxant activities in Swiss albino mice. All the activities were compared with diazepam as a standard drug at a dose of 5 mg/kg. The most active derivatives 5d, 5e, 5k, and 5l in CNS depressant and skeletal muscle relaxant activities were selected for anticonvulsant activity. The active derivatives were found to protect 100% mice at the dose of 6-11 mg/kg, where as standard diazepam protect the animal at a dose of 2.5 mg/kg.
Thore,Gupta, Sunil V.,Baheti, Kamalkishor G.
p. 142 - 149
(2015/01/30)

Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach
Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization.
Shan, Yuanyuan,Gao, Hongping,Shao, Xiaowei,Wang, Jinfeng,Pan, Xiaoyan,Zhang, Jie
p. 80 - 90
(2015/09/15)

Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.
Bollini, Mariela,Casal, Juan J.,Asís, Silvia E.,Leal, Emilse S.,Bruno, Ana M.
p. 1496 - 1503
(2015/04/27)

One-pot and novel route for the synthesis of 4-substituted-1,2,4- triazolidine-3,5-diones
The efficient and one-pot synthesis of 4-substituted-1,2,4-triazolidin-3,5- dione derivatives (4-substituted urazoles) via combination of triphosgene, substituted anilines, and ethyl carbazate in the presence of cesium carbonate is presented.
Ghorbani-Choghamarani, Arash,Nikoorazm, Mohsen,Azadi, Gouhar
supporting information
p. 451 - 454
(2014/03/21)

Metal free oxidative coupling of aryl formamides with alcohols for the synthesis of carbamates
A direct transformation of N-aryl formamides to the corresponding carbamates via the formation of isocyanate intermediates is achieved in good yields using hypervalent iodine as an oxidant. This journal is
Reddy, N. Veera,Prasad, K. Rajendra,Reddy, P. Sudhir,Lakshmi Kantam,Reddy, K. Rajender
supporting information
p. 2172 - 2175
(2014/04/03)

"On water": Efficient iron-catalyzed cycloaddition of aziridines with heterocumulenes
In suspension: The reaction of aziridines with heterocumulenes in the presence of Fe(NO3)3×9 H2O in aqueous suspension provides access to functionalized five-membered heterocycles in good to high yields. This protocol has a wide substrate scope, is simple, and uses a nontoxic and cheap catalyst. Copyright
Sengoden, Mani,Punniyamurthy, Tharmalingam
supporting information
p. 572 - 575
(2013/02/23)

A simple and efficient synthesis of diaryl ureas with reduction of the intermediate isocyanate by triethylamine
Thirty symmetrical diaryl urea derivatives were synthesised in moderate to excellent yields from arylamine and triphosgene with triethylamine as a reducing agent for the intermediate, isocyanate. It was significant that part of the products could be collected in almost quantitative yield without column chromatography. The procedure under mild reaction conditions was tolerant of a wide range of functional groups. The structures of the compounds were determined by NMR, MS and X-ray crystallographic analyses.
Zhou, Shuguang,Yao, Ting,Yi, Jicheng,Li, Dashuai,Xiong, Jing
p. 315 - 319
(2013/07/27)

Synthesis and crystal structure of N-(3-benzylamino-2-cyano-3- methylthioacrylyl)-N′-(substituted phenyl)ureas
Phenylurea groups were introduced into the frame of traditional cyanoacrylate and a series of N-(3-benzylamino-2-cyano-3-methylthioacrylyl)- N′-(substituted phenyl)ureas were synthesized. All compounds are new and their structures were confirmed by 1H NMR, 13C NMR and mass spectral analyses.
Zhong, Shi Hua,Fan, Ming Liang,Liu, Bing Yu,Wei, Dong Mei,Liu, Jian Bing
p. 295 - 300
(2013/07/27)

Mechanism of sulfur transfer from 1,2,4-dithiazolidine-3,5-diones to triphenylphosphines
The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-1,2,4-dithiazolidine-3,5-diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25°C was studied. The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. From the Hammett correlations and from the solvent dependency, it was concluded that the transition-state structure is very polar and resembles the zwitter-ionic intermediate. The extent of P-S bond formation and S-S bond cleavage is very similar in the solvents series, but the latter gradually decreases with the decreasing polarity of the solvent. Copyright 2013 John Wiley & Sons, Ltd. The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-1,2,4-dithiazolidine-3,5- diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25°C was studied. The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. The transition-state structure is very polar and resembles the zwitter-ionic phosphonium intermediate. Copyright
Ponomarov, Oleksandr,Padelkova, Zdenka,Hanusek, Jiri
p. 560 - 564
(2013/07/26)

Synthesis and herbicidal activity of amide derivatives containing thiazole moiety
Twelve novel amide derivatives containing thiazole moiety were synthesized via a coupling reaction of [4-(substituted phenyl)thiazol-2- yl] acetonitrile and aryl isocyanates catalyzed by organic bases. Their structures were characterized by 1H NMR, FTIR, MS and elemental analysis. The preliminary bioassay indicated that these compounds exhibited moderate herbicidal activities against Echinochloa crusgalli and Amaranthus ascedense.
Weng, Jian-Quan,Liu, Xing-Hai,Tong, Guo-Tong
p. 2149 - 2152
(2013/05/09)

N-methylimidazole-catalyzed synthesis of carbamates from hydroxamic acids via the lossen rearrangement
An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.
Yoganathan, Sabesan,Miller, Scott J.
p. 602 - 605
(2013/04/11)

Palladium-catalyzed synthesis of N-aryl carbamates
An efficient synthesis of aryl carbamates was achieved by introducing alcohols into the reaction of palladium-catalyzed cross-coupling of ArX (X = Cl, OTf) with sodium cyanate. The use of aryl triflates as electrophilic components in this transformation a
Vinogradova, Ekaterina V.,Park, Nathaniel H.,Fors, Brett P.,Buchwald, Stephen L.
supporting information
p. 1394 - 1397
(2013/04/24)

Development of synthetic aminopeptidase N/CD13 inhibitors to overcome cancer metastasis and angiogenesis
Cancer metastasis is a major barrier to its treatment and an important cause of patient death. Antimetastatic agents hold promise for patients with advanced metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an important target against cancer metastasis and angiogenesis, but there are few reports on the in vivo evaluation of synthetic APN inhibitors. Herein, a series of compounds targeting APN were synthesized and evaluated for their antimetastasis and antiangiogenesis potency both in vitro and in vivo. Excitingly, compounds 4m, 4t, and 4cc, with the most potent APN inhibitory activities, displayed significant antimetastasis and antiangiogenesis effects in vitro and in vivo, suggesting that those synthetic APN inhibitors have the potential to overcome cancer metastasis and angiogenesis.
Su, Li,Cao, Jiangying,Jia, Yuping,Zhang, Xiaonan,Fang, Hao,Xu, Wenfang
supporting information
p. 959 - 964
(2013/02/23)

Synthesis of unsymmetrical biaryl ureas from N-carbamoylimidazoles: Kinetics and application
N-Carbamoylimidazoles dissociate in solution to yield imidazole and an isocyanate that may be reacted with another aryl amine to form an unsymmetrical biaryl urea. This paper investigates the reaction kinetics and the influence of electron withdrawing/donating substituents on the reaction of N-carbamoylimidazoles with aniline. The overall reaction mechanism involves two zwitterionic intermediates, formed during dissociation and upon reaction of the liberated isocyanate with aniline. The rate limiting step for the reaction is a base catalysed proton transfer from the second zwitterionic intermediate. Although electron withdrawing substituents on the aryl group hinder dissociation, they significantly increase reaction rates compared to compounds bearing electron donating substituents. The imidazole liberated upon dissociation catalyses the rate determining step so that reactions of dissociated N-carbamoylimidazoles proceed more rapidly than those involving only isocyanates. In addition, the imidazole eliminates the need for anhydrous reaction conditions. The N-carbamoylimidazole methodology was demonstrated by preparing sorafenib, a biaryl urea kinase inhibitor, in good yield and excellent purity.
Rawling, Tristan,McDonagh, Andrew M.,Tattam, Bruce,Murray, Michael
experimental part
p. 6065 - 6070
(2012/09/22)

Palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate: A practical synthesis of unsymmetrical ureas
An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive elimination steps of the reaction, including the first demonstration of reductive elimination from an arylpalladium isocyanate complex to produce an aryl isocyanate.
Vinogradova, Ekaterina V.,Fors, Brett P.,Buchwald, Stephen L.
supporting information; experimental part
p. 11132 - 11135
(2012/08/28)

(Tosylimino)phenyl-λ3-iodane as a reagent for the synthesis of methyl carbamates via hofmann rearrangement of aromatic and aliphatic carboxamides
A new, mild procedure for the Hofmann rearrangement of aromatic and aliphatic carboxamides using (tosylimino)phenyl-λ3-iodane, PhINTs, as a reagent is reported. Because of the mild reaction conditions, this method is particularly useful for the Hofmann rearrangement of substituted benzamides, which usually afford complex reaction mixtures with other hypervalent iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols.
Yoshimura, Akira,Luedtke, Matthew W.,Zhdankin, Viktor V.
experimental part
p. 2087 - 2091
(2012/05/05)

1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: Structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain
1,3-Disubstituted ureas possessing a piperidyl moiety have been synthesized to investigate their structure-activity relationships as inhibitors of the human and murine soluble epoxide hydrolase (sEH). Oral administration of 13 1-aryl-3-(1-acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in pharmacokinetic parameters over previously reported 1-adamantylurea based inhibitors. For example, 1-(1-(cyclopropanecarbonyl) piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (52) showed a 7-fold increase in potency, a 65-fold increase in Cmax, and a 3300-fold increase in AUC over its adamantane analogue 1-(1-adamantyl)-3-(1-propionylpiperidin-4-yl) urea (2). This novel sEH inhibitor showed a 1000-fold increase in potency when compared to morphine by reducing hyperalgesia as measured by mechanical withdrawal threshold using the in vivo carrageenan induced inflammatory pain model.
Rose, Tristan E.,Morisseau, Christophe,Liu, Jun-Yan,Inceoglu, Bora,Jones, Paul D.,Sanborn, James R.,Hammock, Bruce D.
supporting information; experimental part
p. 7067 - 7075
(2010/12/25)

Flash vacuum pyrolysis of 1,2,5-oxadiazole 2-oxides and 1,2,3-triazole 1-oxides
The flash vacuum pyrolysis (FVP, 450-600 °C/10-3 mmHg) of 3,4-diaryl- and 3,4-dialkyl-1,2,5-oxadiazole 2-oxides (furoxans) has been investigated. In all cases the 1,2,5-oxadiazole ring cleaved cleanly at O(1)-N(2) and C(3)-C(4) to afford two nitrile oxide fragments, which were trapped in high yield (75-97%) as their isoxazoline cycloadducts by reaction with alk-1-enes. At higher temperatures (700-800 °C) isocyanates were formed as by-products. The dimerisation of acetonitrile oxide to dimethylfuroxan was followed by 1H NMR spectroscopy, and the rate constant for the 2 nd order reaction determined. The furoxans were converted into isocyanates in good yield (61-95%) by FVP, followed by sulfur dioxide-mediated isomerisation of the resulting nitrile oxides. 2,4,5-Trisubstituted-1,2,3- triazole 1-oxides showed greater thermal stability, but at 700-800 °C decomposition of the 4,5-dimethyl compound 25b lead to 1,2-di(5-methyl-2-phenyl- 1,2,3-triazol-2-yl)ethane as the major product; attempts to trap acetonitrile oxide were unsuccessful. ARKAT USA, Inc.
Mitchell, William R.,Paton, R. Michael
experimental part
p. 34 - 54
(2011/02/21)

Synthesis of aryliminoacetonitriles under FVT conditions or by dehydrogenation of arylaminoacetonitriles: an NMR and UV-photoelectron spectroscopy study
The synthesis of [(E)-arylimino]-acetonitriles 3 has been described. It was found that the title compounds can be obtained on the three ways, namely by: (i) dehydrogenation of arylaminoacetonitriles 1, (ii) thermal fragmentation of 1-aryl-4-cyano-β-lactams 4 and (iii) retro-ene reaction of (allyl-p-methoxyphenyl-amino)-acetonitrile (7a) under FVT conditions. 1H and 13C NMR spectra of compounds 3, 5 and 6, and all their precursors 1 and 4, were recorded and analysed in detail using chemical shifts δH and δC [from GIAO DFT B3LYP/6-31(d) calculations] and J-couplings predicted at the DFT B3LYP/IGLO-II level. Also, UV-photoelectron spectra of 4a,d and 3a,d were measured and analysed considering the theoretical evaluation of their ionisation potentials.
Le?niak, Stanis?aw,Chrostowska, Anna,Kuc, Dawid,Maciejczyk, Ma?gorzata,Khayar, Sa?d,Nazarski, Ryszard B.,Urbaniak, ?ukasz
experimental part
p. 10581 - 10589
(2010/02/28)

Synthesis and evaluation of structurally constrained imidazolidin derivatives as potent dipeptidyl peptidase IV inhibitors
To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine derivatives with constrained imidazolidin ring and tested their activities against DPP-IV. Most of them exhibited submicromolar inhibitory activities against DPP-IV. The most potent compound among these is (S)-1-(2-(2-(3-(3,4-dimethoxyphenyl)-2-oxoimidazolidin-1-yl)ethyl-amino)acetyl)pyrrolidine-2-carbonitrile (6n), which is a 2 nM DPP-IV inhibitor.
Wang, Liutang,Zhang, Bin,Ji, Jianxin,Li, Bogang,Yan, Jufang,Zhang, Weiyu,Wu, Yong,Wang, Xuechao
experimental part
p. 3318 - 3322
(2009/12/01)

Carbonyldiimidazole-mediated lossen rearrangement
[Chemical Equation Presented] Carbonyldiimidazole (CDI) was found to mediate the Lossen rearrangement of various hydroxamic acids to isocyanates. This process is experimentally simple and mild, with imidazole and CO 2 being the sole stoichiometric byproduct. Significant for large-scale application, the method avoids the use of hazardous reagents and thus represents a green alternative to standard processing conditions for the Curtius and Hofmann rearrangements.
Dube, Pascal,Fine Nathel, Noah F.,Vetelino, Michael,Couturier, Michel,Aboussafy, Claude Larrivee,Pichette, Simon,Jorgensen, Matthew L.,Hardink, Mark
supporting information; experimental part
p. 5622 - 5625
(2010/03/02)

Synthesis and structure of N-alkyl(aryl)aminocarbonyl-1,4-benzoquinone imines
New N-alkyl(aryl)aminocarbonyl-1,4-benzoquinone imines were synthesized by reaction of isocyanates with the corresponding substituted 4-aminophenols, and their structure was determined on the basis of 1H and 13C NMR spectra and X-ray diffraction data.
Avdeenko,Konovalova,Sergeeva,Zubatyuk,Palamarchuk,Shishkin
experimental part
p. 1765 - 1772
(2009/09/05)

Organometallic chemistry and catalysis on gold metal surfaces
As in transition metal complexes, C{triple bond, long}N-R ligands adsorbed on powdered gold undergo attack by amines to give putative diaminocarbene groups on the gold surface. This reaction forms the basis for the discovery of a gold metal-catalyzed reaction of C{triple bond, long}N-R, primary amines (R′NH2) and O2 to give carbodiimides (R′-N{double bond, long}C{double bond, long}N-R). An analogous reaction of C{triple bond, long}O, RNH2, and O2 gives isocyanates (R-N{double bond, long}C{double bond, long}O), which react with additional amine to give urea (RNH)2C{double bond, long}O products. The gold-catalyzed reaction of C{triple bond, long}N-R with secondary amines (HNR′2) and O2 gives mixed ureas RNH(C{double bond, long}O)NR′2. In another type of gold-catalyzed reaction, secondary amines HN(CH2R)2 react with O2 to undergo dehydrogenation to the imine product, RCH{double bond, long}N(CH2R). Of special interest is the high catalytic activity of gold powder, which is otherwise well-known for its poor catalytic properties.
Angelici, Robert J.
p. 847 - 856
(2008/03/30)

Novel and efficient synthesis of 4-substituted-1,2,4-triazolidine-3,5- diones from anilines
A simple and efficient three-step synthetic procedure for the preparation of 4-substituted phenyl derivatives of 1,2,4-triazolidindiones (urazoles), starting from anilines, has been developed. In this method, aniline derivatives were reacted with 4-nitrophenyl chloroformate to provide corresponding carbamate derivatives. In the second step, semicarbazide derivatives were prepared from these carbamates by reaction with ethyl carbazate. The cyclization reaction of corresponding semicarbazides furnished 1,2,4-triazolidindiones in high yields. Copyright Taylor & Francis Group, LLC.
Mallakpour, Shadpour,Rafiee, Zahra
p. 1927 - 1934
(2008/02/04)

Kinetic and mechanistic study on the thermal reactivity of stabilized phosphorus ylides, part 3: [(Acetyl) (arylcarbamoyl)-methylene] triphenylphosphoranes and [(alkoxy-carbonyl) (arylcarbamoyl)-methylene] triphenylphosphoranes and their thiocarbamoyl analogues
A series of five [(acety])(arylcarbabmoyl)methylene]triphenyl-phosphoranes 1a-e and their thiocarbamoyl analogues 2a-e, |(alkoxycarbonyl)(arylcarbamoyl) methylene]triphenylphosphoranes 3a-e and thiocarbamoyl analogues 4a-e were prepared and fully characterized. All ylides are found under conditions of flash vacuum pyrolysis to fragment giving arylisocyanate or isothiocyanate and acetyl ylides or alkoxy ylides which undergo thermal extrusion of Ph3PO. A kinetic study shows that these reactions are unimolecular and are of first-order nature with no significant substituent effect. The thiocarbamoyl ylides 2 react from 4.6 to 42 times faster than their carbamoyl ylides 1, while the thiocarbamoyl ylides 4 react from 6.6 to 20.9 times faster than their carbamoyl ylides 3.
Aitken, R. Alan,Al-Awadi, Nouria A.,Dawson, Graham,El-Dusouqui, Osman,Kaul, Kamini,Kumar, Ajith
p. 6 - 16
(2008/02/12)