cas 1622-57-7, 2-AMINO-1-METHYLBENZIMIDAZOLE

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2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling
Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro proper-ties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency.
Ferreira, Rafael Augusto Alves,Junior, Celso de Oliveira Rezende,Martinez, Pablo David Grigol,Koovits, Paul John,Soares, Bruna Miranda,Ferreira, Leonardo L. G.,Michelan-Duarte, Simone,Chelucci, Rafael Consolin,Andricopulo, Adriano D.,Galuppo, Mariana K.,Uliana, Silvia R. B.,Matheeussen, An,Caljon, Guy,Maes, Louis,Campbell, Simon,Kratz, Jadel M.,Mowbray, Charles E.,Dias, Luiz Carlos
(2021/03/24)

HMOX1 inducers
The present invention is related to compounds of structure (I) as heme oxygenase 1 (HMOX 1) inducers. The present invention is also related a method of controlling the activity or the amount, or both the activity and the amount, of heme-oxygenase 1 in a mammalian subject. The definitions of the variables are provided herein.
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Page/Page column 21; 159

(2020/09/18)

Hit-to-lead optimization of novel benzimidazole phenylacetamides as broad spectrum trypanosomacides
Trypanosoma cruzi and Trypanosoma brucei are the parasitic causative agents of Chagas disease and human African trypanosomiasis (HAT), respectively. The drugs currently used to treat these diseases are not efficacious against all stages and/or parasite sub-species, often displaying side effects. Herein, we report the SAR exploration of a novel hit, 2-(4-chlorophenyl)-N-(1-propyl-1H-benzimidazol-2-yl)acetamide previously identified from high throughput screens against T. cruzi, Trypanosoma brucei brucei and Leishmania donovani. An informative set of analogues was synthesized incorporating key modifications of the scaffold resulting in improved potency whilst the majority of compounds retained low cytotoxicity against H9c2 and HEK293 cell lines. The SAR observed against T. cruzi broadly matches that observed against T.b. brucei, suggesting the possibility for a broad-spectrum candidate. This class of compounds therefore warrants further investigation towards development as a treatment for Chagas disease and HAT. This journal is
Avery, Vicky M.,Baell, Jonathan,McNamara, Nicole,Rahmani, Raphael,Sykes, Melissa L.
supporting information
p. 685 - 695
(2020/08/24)

Benzimidazole compound and application thereof
The invention relates to a benzimidazole compound and an application thereof. The structure of the benzimidazole compound is shown as a formula I, and the compound is used as a focal adhesion kinase inhibitor and shows relatively good focal adhesion kinase (FAK) inhibition activity. Meanwhile, the benzimidazole compound has stronger medicine effect and better pharmacokinetic property and/or toxicological characteristics, such as good brain/plasma ratio, good bioavailability, good metabolic stability, and reduced inhibition to respiratory action of mitochondria. The benzimidazole compound has agood clinical application prospect.
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Paragraph 0194; 0198; 0199

(2019/01/07)

Metal-free C(sp2)-H functionalization of azoles: K2CO3/I2-mediated oxidation, imination, and amination
The direct C2-H oxidation and imination of a wide variety of azoles was achieved by using a commercially available simple K2CO3/I2 reagent combination. The iodinated azole adduct, produced via the in situ generation of N-heterocyclic carbene, is the key intermediate for C2-H oxidation, imination, and amination of azoles. Significantly, these reactions proceed under mild conditions with high to excellent yields, are scalable to large quantity and exhibit a broad substrate scope. Interestingly, this direct C2-H imination method allowed us to access various pharmacologically active N6-alkyl or N6-aryl substituted benzimidazoquinazolinone scaffolds through intramolecular C-H imination in a sequential one-pot reaction.
Das, Ranajit,Banerjee, Mainak,Rai, Rakesh Kumar,Karri, Ramesh,Roy, Gouriprasanna
p. 4243 - 4260
(2018/06/22)

Synthesis and pharmacological activity of 2-(biphenyl-4-yl)imidazo[1,2-a]benzimidazoles
An efficient method for the synthesis of novel 9H-imidazo[1,2-a]benzimidazole derivatives containing a biphenyl substituent at position 2 was developed. These compounds, belonging to the privileged substructures, have been tested for a wide range of pharmacological activities in the in vitro test panel. It was shown that the synthesized derivatives demonstrated high antioxidant activity, some of them inhibit type 1B protein tyrosine phosphatase, activate AMP-activated protein kinase, possess antiplatelet properties, and a rare and very interesting kind of activity, the ability to break cross-links of glycated proteins. The most active compounds can be suggested for further optimization.
Spasov,Zhukovskaya,Brigadirova,Abbas,Anisimova,Sysoeva,Rashchenko,Litvinov,Mayka, O. Yu.,Babkov,Morkovnik
p. 1905 - 1912
(2018/02/06)

PHOTOREDOX-CATALYZED DIRECT C-H FUNCTIONALIZATION OF ARENES
The invention generally relates to methods of making substituted arenes via direct C-H amination. More specifically, methods of making para- and ortho-substituted arenes via direct C-H amination are disclosed. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00349; 00384

(2017/01/31)

Water compatible photoarylation of amino acids and peptides
A novel photoarylation of amino acids and peptides is described, which tolerates the presence of water. Irradiation of Boc-protected amino acids in the presence of N-protected 2-azidobenzimidazoles leads to selective arylation of carboxy termini or side chains. The new reaction also works for peptides. Irradiation of the nonapeptide H-SPSYVYHQF-OH also resulted in selective arylation of the tyrosine side chains, as indicated by ESI-MS/MS fragmentation. Chemo- and regioselectivity could add the title reaction to the repertoire of photoaffinity labeling methods.
Sudakow, Alex,Papke, Uli,Lindel, Thomas
supporting information
p. 10223 - 10226
(2014/08/18)

Discovery of 2-iminobenzimidazoles as potent hepatitis C virus inhibitors with a novel mechanism of action
In this report we describe 2-iminobenzimidazole (IBI) analogs, identified during the course of a phenotypic high-throughput screening campaign, as novel hepatitis C virus (HCV) inhibitors. A series of IBI derivatives was synthesized and evaluated for their inhibitory activity against infectious HCV. Among the IBIs derivatives studied in this work, we identified promising compounds with high antiviral efficacy, high selectivity index and good microsomal stability. Noteworthy, the IBI series exhibited inhibitory activity on early and late steps of the viral cycle, but not in the HCV replicon system demonstrating a mechanism of action distinct from clinical-stage and approved anti-HCV drugs. Overall, our results suggest that IBIs are predestinated for further exploration as lead compounds for novel HCV interventions.
Windisch, Marc Peter,Jo, Suyeon,Kim, Hee-Young,Kim, Soo-Hyun,Kim, Keumhyun,Kong, Sunju,Jeong, Hyangsuk,Ahn, Sujin,No, Zaesung,Hwang, Jong Yeon
p. 35 - 42
(2014/04/17)

Benzazoles: II.* synthesis and arenesulfonylation of 1-methyl-1H-benzimidazol-2-amine
The reaction of 1-methyl-1H-benzimidazol-2-amine with arenesulfonyl chlorides in the presence of triethylamine afforded 1-arenesulfonyl-3-methyl-2, 3-dihydro-1H-benzimidazol-2-imines instead of expected N-(1-methyl-1H- benzimidazol 2-yl)arenesulfonamides.
Kaipnazarov,Mukhamedov,Okmanov,Berdimbetova,Zhonkhozhaeva
p. 1744 - 1747
(2014/08/05)

Novel N-heterocyclic ylideneamine gold(i) complexes: Synthesis, characterisation and screening for antitumour and antimalarial activity
Ylideneamine functionalised heterocyclic ligands, 1,3-dimethyl-1,3-dihydro- benzimidazol-2-ylideneamine (I), 3-methyl-3H-benzothiazol-2-ylideneamine (II) or 3,4-dimethyl-3H-thiazol-2-ylideneamine (III), were employed in the preparation of a series of both charged and neutral gold(i) complexes consisting either of a Au(C6F5) fragment (1-3), a [Au(PPh3)] + unit (4-6) or a [Au(NHC)]+ unit (7) coordinated to the imine nitrogen of the neutral ylideneamine ligand. These complexes were fully characterised by various techniques including X-ray diffraction. In addition, the antitumour and antimalarial potential of selected compounds were assessed in a preliminary study aimed at determining the medicinal value of such compounds. Complexation of the azol-2-ylideneamine ligands with [Au(PPh3)] + increases their antitumour as well as antimalarial activity.
Coetzee, Jacorien,Cronje, Stephanie,Dobrzanska, Liliana,Raubenheimer, Helgard G.,Joone, Gisela,Nell, Margo J.,Hoppe, Heinrich C.
experimental part
p. 1471 - 1483
(2011/03/16)

Synthesis, characterization and cytotoxicity of some novel 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles
Some new 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles were synthesized using 1-(un)substituted-2-aminobenzimidazoles as precursors in order to determine their cytotoxicity. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Compounds 4, 7-11 and 13-14 were evaluated for their cytotoxical effect on two cancer cell lines: human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231 and as well as normal spleen cells. The distinctly marked antiproliferative activity of 1,3-bis(3-phenylpropyl-1)-1,3-dihydro-2H-benzimidazol-2-imine hydro bromide 7, N-(aminopropyl)-2-(3-{2-[(aminopropyl)-amino]-2-oxoethyl}-2-imino-2, 3-dihydro-1H-benzimidazol-1-yl)acetamide 9 and 1,3-bis[2-(4-methylpiperazin-1- yl)-2-oxoethyl]-2,3-dihydro-2H-benzimidazol-2-imine 11 against human colorectal cancer cell line HT-29 was ascertained and the calculated IC50 were 9.26, 0.56 and 0.013 nM respectively. Compounds 4, 9, 10 and 13 exhibited relative high cytotoxic activity against MDA-MB-231 cells. The calculated IC50 values were in the range 0.123-1.65 nM. All tested compounds excluding compound 1,3-bis[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2,3-dihydro- 2H-benzimidazol-2-imine (11) revealed proliferative activities to normal spleen cells. The computed EC50 values varied from 0.05 to 16.91 nM.
Mavrova, Anelia Ts.,Wesselinova, Diana,Vassilev, Nikolay,Tsenov, Jordan A.
body text
p. 3362 - 3367
(2011/07/29)

FUSED PYRIMIDINEONE COMPOUNDS AS TRPV3 MODULATORS
The present invention provides transient receptor potential vanilloid (TRPV) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPV3. Also provided herein are pro
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Page/Page column 21

(2009/12/05)

Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3
High-throughput screening identified a low molecular weight antagonist of CXCR3 displaying micromolar activity in a membrane filtration-binding assay. Systematic modification of the benzimidazole core and tethered acetophenone moiety established tractable SAR of analogs with improved physicochemical properties and sub-micromolar activity across both human and murine receptors.
Hayes, Martin E.,Wallace, Grier A.,Grongsaard, Pintipa,Bischoff, Agnieszka,George, Dawn M.,Miao, Wenyan,McPherson, Michael J.,Stoffel, Robert H.,Green, David W.,Roth, Gregory P.
p. 1573 - 1576
(2008/09/21)

Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3
Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in compounds with improved in-vitro species selectivity. Incorporation of an 8-quinoline amide and conformational rigidification of an aliphatic tether furnished potent compounds suitable for further lead optimization.
Hayes, Martin E.,Breinlinger, Eric C.,Wallace, Grier A.,Grongsaard, Pintipa,Miao, Wenyan,McPherson, Michael J.,Stoffel, Robert H.,Green, David W.,Roth, Gregory P.
p. 2414 - 2419
(2008/09/20)

Synthesis and antitrichinellosis activity of some bis(benzimidazol-2-yl)amines
Novel bis(benzimidazol-2-yl)amines were synthesized using two methods and studied for antitrichinellosis activity. DFT calculations were performed in order to determine the geometry of molecules. All derivatives of 2-aminobenzimidazole exhibited higher activity in vitro against Trichinella spiralis larvae in regard to the activity of albendazole, moreover compounds 4f-i manifested antitrichinellosis effect, which surpassed five times the activity of albendazole. The in vivo screening of intestinal phase of the T. spiralis revealed 100% effectiveness of compounds 4g-i at oral dosages of 50 and 100 mg/kg mw, while albendazole possesses 100% efficacy only at a dose of 100 mg/kg mw.
Mavrova, Anelia Ts.,Denkova, Pavletta,Tsenov, Yordan A.,Anichina, Kameliya K.,Vutchev, Dimitar I.
p. 6291 - 6297
(2008/04/05)

Synthesis and some conversions of N-substituted benzimidazole-2-sulfonic acids
A series of N-substituted benzimidazole-2-sulfonic acids was synthesized in good yield by the N-alkylation of benzimidazole-2-sulfonic acids by alkylation with simple and functionalized alkylating agents under mild conditions. The corresponding N-substitu
Divaeva,Kuzmenko,Morkovnik,Komissarov
p. 463 - 468
(2008/02/02)

Synthesis and?QSAR studies of?novel 1-substituted-2-aminobenzimidazoles derivatives
A series of novel 1-substituted-2-aminobenzimidazole derivatives were synthesized. The structures of the synthesized compounds were confirmed by 1H-NMR spectra and by elemental analysis. Acute toxicities of these compounds were detected on mice via toxicity (logLD50). QSAR analysis of these chemicals was studied on the relationship between acute toxicity and the octanol/water partition coefficient (LogP). The products were identified by the results of elemental analysis and 1H-NMR spectra. The toxicity (logLD50) of 2-aminobenzimidazole 1-substituents were correlated well with the partition coefficient LogP, r = 0.9243. The bioactivity (toxicity) of 2-aminobenzimidazoles can be predicted by the molecular structural parameter such as LogP.
Guida, Xuan,Jianhua, Han,Xiaomin, Li
p. 1080 - 1083
(2007/10/03)

Total syntheses of naamine A and naamidine A, marine imidazole alkaloids
The first total syntheses of naamine A (4) and naamidine A (5), marine imidazole alkaloids, were achieved through twelve and thirteen steps of reactions, respectively, starting from 1-methyl-2-phenylthio-1H-imidazole (17).
Ohta, Shunsaku,Tsuno, Naoki,Nakamura, Seikou,Taguchi, Norio,Yamashita, Masayuki,Kawasaki, Ikuo,Fujieda, Mieko
p. 1939 - 1955
(2007/10/03)

Electrosynthesis and studies of adducts of 2-amino-1-methylbenzimidazole with metal chelates based on 2-tosylammo-N-salicylideneaniline
For the first time the adducts of 2-amino-1-methylbenzimidazole (L) with cobalt, copper, and zinc chelates based on 2-tosylamino-N-salicylideneaniline were electrochemically synthesized, and the properties and structures of these adducts were studied. According to the IR and 1H NMR spectral data on the adducts obtained and X-ray structural analysis of the copper complex, the adducts of composition mL · ML′ · nH2O (m = 1 or 2; n = 0, 1, or 2) contain the L moiety bonded to the metal atom through the pyridine-type N atom of the imidazole ring.
Garnovskii,Sousa,Antsyshkina,Sadikov,Vasil'chenko,Sigeikin,Burlov,Castineiras,Garnovskii
p. 1988 - 1992
(2007/10/03)

Highly effective procedure for introduction of amino group into the 2-position of imidazole ring
Procedures for the preparation of 2-amino- and 2-arylaminobenzimidazoles were developed, and one of the efficient procedure was applied to the synthesis of preclathridine A, a marine imidazole alkaloid isolated from a sponge.
Kawasaki, Ikuo,Taguchi, Norio,Yoneda, Youko,Yamashita, Masayuki,Ohta, Shunsaku
p. 1375 - 1379
(2007/10/03)

OXIDATIVE CYCLIZATION OF 2-AMINO-1-ARYLIDENEAMINOBENZIMIDAZOLES INTO 1,2,4-TRIAZOLOBENZIMIDAZOLES
When heated in nitrobenzene, 1-arylideneamino-2-methylaminobenzimidazoles convert in a 20...30percent yield into 2-aryl-3-methyl-1,2,4-triazolobenzimidazoles.In addition, 2-methylaminobenzimidazole and the corresponding benzonitrile are formed as a result of thermal splitting of the N-N bond.Under the same conditions, 2-amino-1-arylideneaminobenzimidazoles and 1-arylideneamino-3-methylbenzimidazoline-2-imines give only products of splitting off of the nitrile.In several cases, the subsequent reaction of the nitrile with 2-amino-1-methylbenzimidazole leads to the formation of benzamidines.
Kuz'menko, T. A.,Kuz'menko, V. V.,Pozharskii, A. F.,Klyuev, N. A.
p. 1012 - 1017
(2007/10/02)

Nucleophilic Substitution in Quaternary Salts of NN'-Linked Biazoles and Related Systems.
Some reactions of dicationic and monocationic N,N'-linked biazoles and of quaternized 1-(N-azolyl)pyridinium ions with nucleophiles have been studied.Although the pyrrolyl nucleus has been found to be a poor leaving group in these reactions, in other cases nucleophilic attack readily takes place at an azolyl carbon atom, with subsequent elimination of the N-substituent.The 1-methyl-3-(1-methyl-1,2,4-triazol-4-ylio)benzimidazolium dication (1) reacted at room temperature with ammonium, diethylamine, methoxyde, hydroxide, and cyanide ions, and with sodium borohydride, giving in all cases the corresponding 2-substituted benzimidazoles in good yield.In the case of the 2,4,6-trimethyl-1-(2-methylpyrazol-1-io)pyridinium dication (6), the reaction with cyanide ion afforded, regioselectively, 5-cyano-1-methylpyrazole, with no trace of the isomeric 3-cyano-1-methylpyrazole.The synthesis of the cations and dications from N-aminoazoles was easily performed.The reaction of 1-aminobenzimidazole with dehydroacetic acid in aqueous hydrochloric acid gave not only the expected 1-benzimidazol-1-yl-2,6-dimethylpyridin-4(1H)-one (9), but also 3-acetyl-1-benzimidazol-1-yl-4-hydroxy-6-methylpyridin-2(1H)-one (11).In pyridine, a pyran-2,4-dione intermediate (10), isomeric to (11), was also isolated.The quaternization reactions were easily performed, but high temperatures caused cleavage of the N-N bond.
Castellanos, Maria Luisa,Llinas, Montserrat,Bruix, Marta,Mendoza, Javier de,Martin, M. Rosario
p. 1209 - 1216
(2007/10/02)

REDUCTION OF BENZIMIDAZOLE-2-SULFONIC ACIDS
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Popov, I. I.,Boroshko, S. L.,Tertov, B. A.
p. 224
(2007/10/02)

A Facile N-Alkylation of Imidazoles and Benzimidazoles
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Kikugawa, Yasuo
p. 124 - 125
(2007/10/02)

Iminoisoindolinone metal complex
Iminoisoindolinone metal complexes of formula STR1 wherein A represents a 5- or 6-membered heterocyclic radical which contains at least one further heteroatom and can be fused or doubled with benzene nuclei, M represents a divalent metal atom excluding the alkaline earth metals, X represents a hydrogen atom, Y represents a halogen atom, Z represents a nitro group, an alkoxycarbonyl group of 2 to 6 carbon atoms or a group of formula RY2 --, wherein R represents a hydrogen atom, an alkyl group of 1 to 6 carbon atoms which is substituted by an aryl radical or is unsubstituted, a cycloalkyl group of 5 to 6 carbon atoms, or represents an aryl group, and Y2 represents an oxygen or a sulphur atom, m and n are 0 to 4, p is 0 to 2, and the sum of m+n+p must be 4, which are useful for pigmenting high molecular organic material.
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(2008/06/13)