- Method for synthesizing clonazepam compound
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The invention discloses a method for synthesizing a clonazepam compound, and belongs to the technical field of organic chemical synthesis, and the preparation method comprises the following steps: by taking 2-amino-4-nitrophenyl potassium trifluoroborate as an initial raw material, carrying out oxidative coupling, amidation, affinity substitution reaction, intramolecular condensation reaction and the like to obtain a target compound; the method disclosed by the invention is short in synthesis step, safe to operate and simple and convenient in post-treatment, and the product can be obtained by directly filtering and leaching without other purification; only conventional acid, alkali and solvents are used in the whole reaction process, the cost is low, and the yield is increased by 30% or above.
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Paragraph 0024; 0026-0031
(2021/07/24)
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- Novel method for preparing 7-amino clonazepam compound
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The invention discloses a novel method for preparing a 7-amino clonazepam compound, and belongs to the technical field of organic synthesis. The preparation method comprises the steps that 2-amino-4-nitrobenzoic acid serves as an initial raw material, and a target compound is obtained through the processes of acetyl-lactonization, Grignard reaction, amide hydrolysis, intramolecular condensation reaction, reduction and the like. The method provided by the invention is safe to operate, avoids the use of heavy metals, is simple and convenient in post-treatment, can obtain the product through direct filtration and recrystallization, and does not need other purification. Only conventional acid, alkali and solvents are used in the whole reaction process, so that the method is less in environmental pollution, low in cost and higher in yield.
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Paragraph 0042-0043; 0050-0052
(2021/07/08)
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- Method for synthesizing 7-amino clonazepam compound
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The invention discloses a method for synthesizing a 7-amino clonazepam compound, and belongs to the technical field of organic synthesis. The preparation method comprises the steps that 2-cyano-4-nitroaniline serves as an initial raw material, and a target compound is obtained through oxidative coupling, amidation, affinity substitution reaction, intramolecular Wittig reaction, reduction reaction and other processes. According to the invention, a brand new synthetic route is provided for 7-amino nitrazepam, the method has the advantages of short synthetic steps, safe operation and simple post-treatment, only conventional acid-base and solvent are used in the whole reaction process, the cost is low, and the yield is increased by more than 20%.
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Paragraph 0035-0039; 0056-0059
(2021/07/08)
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- 10-(4-Phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and related compounds: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
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As part of our continuing search for potent inhibitors of tubulin polymerization, two novel series of 42 10-(4-phenylpiperazine-1-carbonyl)acridin-9(10H)-ones and N-benzoylated acridones were synthesized on the basis of a retrosynthetic approach. All newly synthesized compounds were tested for antiproliferative activity and interaction with tubulin. Several analogs potently inhibited tumor cell growth. Among the compounds tested, 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)acridin-9(10H)-one (17c) exhibited excellent growth inhibitory effects on 93 tumor cell lines, with an average GI50 value of 5.4 nM. We were able to show that the strong cytotoxic effects are caused by disruption of tubulin polymerization, as supported by the EBI (N,N'-Ethylenebis(iodoacetamide)) assay and the fact that the most potent inhibitors of cancer cell growth turned out to be the most efficacious tubulin polymerization inhibitors. Potencies were nearly comparable or superior to those of the antimitotic reference compounds. Closely related to this, the most active analogs inhibited cell cycling at the G2/M phase at concentrations down to 30 nM and induced apoptosis in K562 leukemia cells. We believe that our work not only proves the excellent suitability of the acridone scaffold for the design of potent tubulin polymerization inhibitors but also enables synthetic access to further potentially interesting N-acylated acridones.
- Waltemate, Jana,Ivanov, Igor,Ghasemi, Jahan B.,Aghaee, Elham,Daniliuc, Constantin Gabriel,Müller, Klaus,Prinz, Helge
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- Design, synthesis and evaluation of aminobenzophenone derivatives containing nitrogen mustard moiety as potential central nervous system antitumor agent
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A series of novel substituted aminobenzophenone derivatives containing nitrogen mustard moiety (5a-f) were synthesized and characterized on the basis of their IR, 1H NMR, 13C NMR, CHN, and mass spectral data. All the compounds when evaluated for chemical 4-(4-nitrobenzyl) pyridine alkylating activity proved to be active alkylating agents. All the synthesized compounds were subjected to physicochemical parameters determination required for central nervous system (CNS) activity through computational, online software, and QikProp 3.2. The log P values and other in silico ADME physicochemical descriptors analyzed lay between the ranges those are required for good BBB penetration. The in vitro antiproliferative activity against human cancer cell lines viz. A 549 (lung), COLO 205 (colon), U 87 (glioblastoma), and IMR-32 (neuroblastoma) was investigated. Most of the test compounds showed potent antitumor activity, especially compound (5f) which displayed the highest activity against CNS cancer cell line comparable to that of chlorambucil and docetaxel. The preliminary structure-activity relationship (SAR) revealed that 5-chloroaminobenzophenone-mustard series (5a-c) exhibited better antitumor activity than 5-nitroaminobenzophenone-mustard series (5d-f).
- Singh, Rajesh K.,Prasad,Bhardwaj
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p. 5901 - 5911
(2013/11/06)
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- (Benzoylphenyl)piperidines: A new class of immunomodulators
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A series of (benzoylphenyl)piperidines has been synthesized and evaluated for activity as immunomodulators. Several of these compounds show good activity in primary screening on the basis of the lymphocytes mitogenic response to Con A, PHA, and PWM. A chloro group in position 4 of the benzoyl moiety as well as an amino group (or a carbamate derivative) para to the piperidine nucleus seems to be essential for activity. The depicted compounds may be considered as the first examples of a new series of immunomodulators.
- Bellamy,Chazan,Dodey,Dutartre,Ou,Pascal,Robin
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p. 1545 - 1552
(2007/10/02)
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- Studies on the detection of clonazepam and its main metabolites considering in particular thin-layer chromatography discrimination of nitrazepam and its major metabolic products (author's transl)
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The article describes analytical methods concerning screening tests for clonazepam and nitrazepam and the 7-amino derivatives. Further a detailed method is reported for the separation and identificatin of the benzodiazepine pair de. The method described permits a sharp separation and the nitro compounds with TiCl3 on the plate and forming the 7-acetamido derivatives by subsequent separation in the second dimension with ethyl acetate/acetic anhydride. The method described permits a sharp separation and highly sensitive detection by diazotization and coupling with Bratton-Marshall reagent. Amounts as low as 0.02 microng per spot can be detected. Besides preparation methods are reported for 7-aminoclonazepam, 7-acetaminoclonazepam, 2-amino-2'-chloro-5-nitrobenzophenone and 2,5-diamino-2'-chlorobenzophenone. Also spectral data (UV, IR, MS) and a literature review are given.
- Ebel,Schuetz
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p. 325 - 337,327,330,332,334
(2007/10/05)
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