- Novel synthetic bisbenzimidazole that targets angiogenesis in Ehrlich ascites carcinoma bearing mice
-
Abstract Cancer is a leading cause of death in developed countries and second cause in developing countries. Herein we are reporting the synthesis of novel bisbenzimidazole derivatives and their anticancer properties. Among the newly synthesized bisbenzimidazoles, 3-(4-flurophenylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole (FDPB) presented as a potent antiproliferative agent against HeLa, HCT116 and A549 cells with selectivity over normal Vero cells (IC50 >50 μM). Additionally, we evaluated the efficacy of lead compound against Ehrlich ascites tumor (EAT) bearing mice for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature and production of Vascular Endothelial Growth Factor (VEGF).
- Roopashree, Rangaswamy,Mohan, Chakrabhavi Dhananjaya,Swaroop, Toreshettahally Ramesh,Jagadish, Swamy,Raghava, Byregowda,Balaji, Kyathegowdanadoddi Srinivas,Jayarama, Shankar,Basappa,Rangappa, Kanchugarakoppal Subbegowda
-
-
Read Online
- Novel preparation method of antihypertensive drug telmisartan intermediate
-
The invention relates to an electric reduction preparation method of aminobenzoic acid represented by formula I and ester thereof. The preparation reaction of the method is shown in the description; and in the reaction formula, R is selected from hydrogen, a methyl group, an ethyl group, a benzyl group, a C3 or C4 straight-chain alkyl or branched-chain alkyl group, -NO2 is selected from 4-NO2 or 5-NO2, and Y is selected from H or 4-NHCOC3H7-n. The electroreduction preparation method of aminobenzoic acid and ester I thereof is characterized in that in a separated electrolytic cell, an acidic solution of nthe itrobenzoic acid and ester III thereof is taken as a catholyte; the voltage of a cathode working electrode relative to a reference electrode is 1.00-2.50 V; and an anolyte is an acidicsolution, the current density is 25.0-250.0 mA/cm, and the electrolysis temperature is 15-90 DEG C.
- -
-
Paragraph 0081-0084
(2021/06/26)
-
- Design, synthesis and biological evaluation of AT1 receptor blockers derived from 6-substituted aminocarbonyl benzimidazoles
-
A series of new 6-substituted aminocarbonyl benzimidazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole moiety and benzoic acid moiety were designed, synthesized and pharmacologically evaluated. Most of the synthesized compounds could bind to the AT1 receptor and decrease blood pressure significantly. Notably, 2e and 1h could obviously decrease MBP in a dose dependent manner. The maximal response lowered 57.9 ± 2.3 mmHg (2e) and 57.6 ± 1.9 mmHg (1h) of MBP at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan (Fig. 1). These results indicate that 2e and 1h are effective and long-lasting anti-hypertension drug candidates and deserve further investigation for therapeutic application.
- Wu, Zhuo,Anh, Nguyen Thi Phuong,Yan, Yi-Jia,Xia, Ming-Bao,Wang, Yan-Hui,Qiu, Yan,Chen, Zhi-Long
-
-
- Design, Synthesis, and Biological Evaluation of 6-Benzoxazole Benzimidazole Derivatives with Antihypertension Activities
-
A series of new angiotensin II receptor 1 antagonists were prepared. They displayed nanomolar affinity to AT1 receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. Among them, compounds 1b and 2b could reduce the blood pressure with more or equal potency compared to Losartan. So, compounds 1b and 2b could be considered as potential antihypertension drug candidates.
- Wu, Zhuo,Bao, Xiao-Lu,Zhu, Wei-Bo,Wang, Yan-Hui,Phuong Anh, Nguyen Thi,Wu, Xiao-Feng,Yan, Yi-Jia,Chen, Zhi-Long
-
-
- N-Phenyl indole derivatives as AT1 antagonists with anti-hypertension activities: Design, synthesis and biological evaluation
-
The design, synthesis, in vitro and in vivo evaluation of 6-substituted benzimidazole with 1, 4-disubsituted or 1, 5-disubsituted indole derivatives as novel angiotensin II receptor antagonists are outlined. Radioligand binding assays showed that several 6-substituted benzimidazole derivatives displayed high affinities binding to the angiotensin II type 1 receptor at the same order of magnitude to telmisartan. The biological evaluation on spontaneously hypertensive rats showed that 2-[4-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole-1-yl]methyl]-1H-indol-1-yl]benzoic acid, 1c, could cause significant decrease on MBP in a dose dependent manner. Its maximal response lowered 53 mmHg of MBP at 5 mg/kg and 64 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which was better than both losartan and telmisartan. A study designed to determine acute toxicity showed that 1c had low acute toxicity with no significant changes in the weight and no obvious untoward reactions. The encouraging results make 1c an effective and durable anti-hypertension drug candidate and deserve further investigation for therapeutic application.
- Zhu, Weibo,Bao, Xiaolu,Ren, He,Da, Yajing,Wu, Dan,Li, Fuming,Yan, Yijia,Wang, Li,Chen, Zhilong
-
p. 161 - 178
(2016/04/05)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF TELMISARTAN
-
Methyl-4-(butyramido)-3-methyl-5-nitrobenzoate is treated with sulphur containing reducing agent to give methyl-4-methyl-2-propyl-lH-benzimidazole-6-carboxylate, which is further hydrolyzed to the corresponding acid, 2-n-propyl-4-methyl-6- carboxy benzimidazole. The critical intermediate l,4'-dimethyl-2'-propyl-lH,3'H- 2,6'-bisbenzimidazol (DMPBB) is prepared by treating the above acid with N- mehtyl-o-phenylenediamine dihydrochloride under acidic conditions. Reaction of 4'-halomethylbiphenyl-2-carboxylic acid alkyl ester with DMPBB in presence of base to give Telmisartan ester which is further converted to Telmisartan of Formula (I).
- -
-
Page/Page column 11
(2012/03/26)
-
- PROCESS FOR PREPARING TELMISARTAN
-
Novel processes for preparing a telmisaitan nitrile intermediate (4'-[{2-n-propyl-4- methyI-6-f l-methyJbenzimidazol-2-yl)-benzimidazol- l -yl)-methyl]-biphenyl-2-nitrile) and further converting it to telmisaitan and/or salts thereof are disclosed.
- -
-
Page/Page column 13; 40
(2009/03/07)
-
- NOVEL INTERMEDIATES AND METHOD FOR SYNTHESIS OF 4'-[(1,4'-DIMETHYL-2'-PROPYL-[2,6'- BI-1HBENZIMIDAZOL]-L-YL)METHYL]-1,1-BIPHENYL]-2-CARBOXYLIC ACID.
-
Disclosed herein is a method for synthesis of 4'-[(1,4'-dimethyl-2'-propyl-[2,6'-bi- 1H]benzimidazol]-l-yl)methyl]-[1,1-biphenyl]-2-carboxylic acid or its derivatives, and novel intermediate compounds useful in the synthesis.
- -
-
Page/Page column 17-18
(2009/10/22)
-
- PROCESS FOR PREPARATION OF TELMISARTAN
-
A process for preparation of telmisartan comprises: (i) oxidation of compound of formula (a), wherein R2 is a hydrogen atom or a substituent of formula (b), in which R1 is a protecting group for the carboxyl function, to an aldehyde of formula (c), in which R2 is defined as in the formula (a), and, optionally, (ii) in case R2 in the compound (c) thus obtained is a hydrogen atom, iV-alkylation of the compound (c) with a biphenyl derivative, (iii) treatment of the compound (c) thus obtained with N- methyl- o-nitroaniline in a cyclocondensation reaction, and (iv) cleavage of the protecting group R1.
- -
-
Page/Page column 11
(2009/10/30)
-
- Dual-acting benzoimidazole antihypertensive agents
-
The invention is directed to compounds having the formula: wherein: Ar, r, n, X, R2-3 and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
- -
-
Page/Page column 44
(2009/01/24)
-
- Facile Synthesis of Novel Nonpeptide Angiotensin II Receptor Antagonists
-
A series of Losartan analogues 1-12 with different functional groups were synthesized and characterized. In comparison with the previous reports, the synthetic procedures described in this paper have been optimized as follows below: 1) preparation of aromatic amine 15 and 18 through hydrogenation by employing Raney Ni and hydrazine as catalysts in place of palladium; 2) preparation of nitro-compound 17 by using pure fuming nitric acid at -20 - -15°C; 3) alkylation of 21 with 22 or 23 in the presence of sodium hydride in place of potassium tert-butylate; 4) preparation of carboxylic acid 4 by ester cleavage rather than hydrolysis of cyano group.
- Yang, Ling-Chun,Qi, Chuan-Min,Zhang, Guan-Xin,Zou, Nan-Zhi
-
p. 1107 - 1112
(2007/10/03)
-
- 6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: Synthesis, biological activity, and structure-activity relationships
-
Starting from the recently reported nonpeptidic angiotensin II (AII) receptor antagonists DuP 753 (1) and Exp 7711 (2), we have designed and investigated novel substituted benzimidazoles. Systematic variation of several substituents at the benzimidazole ring positions 4-7 led to the finding that substitution in position 6 with acylamino groups results in highly active AII antagonists. Compounds with 6-membered lactam or sultam substituents in position 6 of benzimidazole showed receptor activities in the low nanomolar range but were only weakly active when given orally to rats. In contrast, analogous substitution of the benzimidazole moiety with basic heterocycles resulted in potent AII antagonists which were also well absorbed after oral application. The most active compound of this series, 33 (BIBR 277), was selected as a candidate for clinical development. On the basis of molecular modeling studies a binding model of this new class of AII antagonists to the AT1 receptor is proposed.
- Ries,Mihm,Narr,Hasselbach,Wittneben,Entzeroth,Van Meel,Wienen,Hauel
-
p. 4040 - 4051
(2007/10/02)
-
