36 results about "Nitroimidazole derivatives" patented technology

The invention relates to a process for preparing optical enantiomers of nitroimidazole derivatives and the use of these compounds in preparing anti anaerobe medicaments.

The invention relates to an F-1,2,3-triazole ring-polyethylene glycol-metronidazole compound which has the following structural general formula: L is ethyl or polyethylene glycol with the following structure: n is equal to 0, 1, 2 or 3; M is a triazole ring with the following structure: or, N is ethyl or polyethylene glycol with the following structure; n is equal to 0, 1, 2 or 3; and A is 19F or18F. Under a changeless condition that the invention keeps the metronidazole as a targeting base group, the polyethylene glycol is introduced to modify and change the molecular structure of a medicine, and the aims of improving medicine dynamics and pharmacodynamical properties and increasing the curative effect of the medicine are achieved. The triazole ring, a PEG base group, 2- metronidazole and 18 / 19F nuclide are connected by a click method, and a series of novel F-triazole ring-PEG-metronidazole derivatives are designed and synthesized. The nitro imidazole derivatives can quicken removing from normal tissues by lowering fat solubility so as to enhance a target / non-target ratio and is used for the development research of tumours, cardiac muscles or brain anoxia.

The present invention relates to disease treating nitroimidazole derivative, and the compound may be used in preparing medicine for resisting anaerobic bacteria and trichomonas.

The invention discloses an on-line nitroimidazole derivative synthesis method by adopting lipase catalysis. The on-line nitroimidazole derivative synthesis method by adopting lipase catalysis comprises the following steps: taking imidazole compounds and acrylate compounds as raw materials, wherein mass ratio of the imidazole compounds to the acrylate compounds is 1 to (1-5); taking 0.5-1.0 gram oflipase Lipozyme RM IM as a catalyst, as well as a DMSO solvent as a reaction solvent; uniformly filling a reaction channel of a microfluidic channel reactor with the lipase Lipozyme RM IM, wherein the inner diameter of the reaction channel of the microfluidic channel reactor is 0.8-2.4 millimeters and the length of the reaction channel is 0.5-1.0 meter; continuously introducing the raw materialsand the reaction solvent into the reaction channel so as to be subjected to Michael addition reaction for 25-40 minutes, wherein the temperature of the Michael addition reaction is controlled at 40-55DEG C; collecting reacted solution on line; and then, performing conventional post-processing on the reacted solution so as to obtain nitroimidazole derivatives. The on-line nitroimidazole derivativesynthesis method disclosed by the invention has the advantages of being short in reaction time, excellent in selectivity and high in yield.

The invention relates to a novel F-triazole ring-PEG-2-nitroimidazole compound and a preparation method thereof, and the structural general formula of the compound is shown on the right. A triazole ring, a PEG group, 2-nitroimidazole and a <18 / 19>F nuclide are connected by using nitroimidazole as a targeting group by a click method, and are designed to synthesize a series of novel F-triazole ring-polyethyleneglycol-2-nitroimidazole derivatives, and the nitroimidazole derivative is used as a novel compound capable of improving the metabolic property of medicaments and is used for PET anaerobic visualization studies.

The invention relates to a nitroimidazole derivative used in therapy, and provides a compound of formula (I) or its pharmaceutical salt: wherein R1 can be taken as saturated or unsaturated straight chain, branched chain alkyl or cyclic alkyl with the carbon number from 1 to 10, R2, R3 can represent alkyl or form rings, the ring can be the ring from three-membered ring to ten-membered ring, the ring is capable of connecting with one or a plurality of same or different substituents; the rings formed by R2, R3 are capable of forming heterocycles, the heterocycle is capable of containing 0 to 5 same or different heteroatom substitutions; X expresses ion or group with negative electricity, which concretely can be halogen negative ion, organic acid radical, inorganic acid radical. According to the invention, the nitroimidazole derivative is used for treating the diseases caused by anaerobic infection or protozoans infection.

The invention discloses a radioactive drug and a preparation method thereof. The compound is fluo-polyethylene glycol-triazole ring-methylene-2metridazloe, and the structural general formula of the compound is disclosed in the specification, wherein n is 1-10, and F is 18F. The preparation method comprises the following steps of: adding 2-metridazloe, propargyl bromide and K2CO3 to CH3CN; heating for refluxing; adding a product obtained after sufficient reaction, a product obtained by adding di-p-tolyl-sulphonate of polyethylene glycol and NaN3 to DMF (Dimethyl Formamide) and heating with boiled water, CuI and Et3N to THF (Tetrahydrofuran); and finally carrying out a clink reaction on the two products to finally obtain a [18F]FPEGn-TAN solution.

The invention relates to a new method for synthesizing an ornidazole derivative, namely benzoyl ornidazole. At present, ornidazole is a third-generation novel nitroimidazole derivative after metronidazole and tinidazole, has high anaerobe resistance and protozoan resistance, but is difficultly applied to children because of bitter taste. The invention aims to provide a new method for synthesizing the ornidazole derivative. The synthesis method comprises the following steps of: adding ornidazole, fatty acid and fatty alcohol ester, and aliphatic tertiary amine or nitrogen heterocycle organic base in turn, stirring for dissolution and clarification, heating to refluxing temperature, dripping benzoyl chloride, and reacting by keeping temperature under normal pressure; cooling, adding water, stirring, standing for demixing, adding water to wash an organic phase, cooling and freezing for crystallization, filtering, washing, and drying to obtain a crude product; and recrystallizing the crude product by using ethanol to obtain the benzoyl ornidazole. The method has the advantages that: the obtained benzoyl ornidazole is a precursor medicine of ornidazole, the original bitter taste of the ornidazole is eliminated, and a method for industrially producing the benzoyl ornidazole is realized.

The invention provides synthesis of 1-indoleacetic acid-5-nitroimidazole-containing derivative. The derivative is characterized by having a general formula as shown in the specification, wherein R is 3a:o-Cl; 3b:m-Cl; 3c:p-Cl; 3d:o-Br; 3e:m-Br; 3f:p-Br; 3g:o-NO2; 3h:m-NO2; 3i:p-NO2; 3j:o-CH3; 3k:m-CH3; 3l:p-CH3; 3m:o-OCH3; 3n:m-OCH3; 3o:p-OCH3; 3p:2,4-2Cl; 3q:fused Ph; 3r:H. The 1-indoleacetic acid-5-nitroimidazole-containing derivative has a remarkable inhibiting effect on a human lung adenocarcinoma cell line (A549), a human cervical carcinoma cell line (HELA) and a human astrocytoma cell line (U251), and can be applied to preparation of anti-tumor medicines. The invention further discloses a preparation method of the derivative.

The invention discloses an on-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry. The on-line phenylethanol beta-amino-alcohol derivative synthesis method on basis of enzymatic aminolysis by flow chemistry comprises the following steps: taking methanol as a reaction solvent, aniline compounds and styrene oxide as raw materials, wherein the molar ratio of the aniline compounds to the styrene oxide is 1 to (0.6-1.4), and lipase Lipozyme RM IM as a catalyst; putting the raw materials and the reaction solvent into a syringe; uniformly filling a reaction channel of a microfluidic channel reactor with the lipase Lipozyme RM IM and continuously introducing the raw materials and the reaction solvent into the reaction channel under push force of an injection pump so as to be subjected to ring-opening reaction, wherein the inner diameter of the reaction channel of the microfluidic channel reactor is 0.8-2.4 millimeters and the length of the reaction channel is 0.5-1.0m; carrying out ring-opening reaction at 30-50 DEG C for 10-30 minutes, and collecting reacted solution on line by using a product collector; and then, performingconventional post-processing on the reacted solution so as to obtain phenylethanol beta-amino-alcohol derivatives. The on-line nitroimidazole derivative synthesis method disclosed by the invention has the advantages of being short in reaction time, excellent in selectivity and high in yield.

The invention discloses a substituted nitroimidazole derivative, which is mainly used for treating related diseases caused by mycobacterium infection, such as Mycobacterium tuberculosis, especially for diseases caused by drug-resistant Mycobacterium tuberculosis.

To provide a pharmaceutical composition containing a 2-nitroimidazole derivative, which has high solubility in an aqueous carrier and high stability.The pharmaceutical composition is characterized by containing 1-(1-hydroxymethyl-2,3-dihydroxypropyl)oxymethyl-2-nitroimidazole and creatinine, and containing creatinine of 0.001 to 1 part by mass with respect to 1 part by mass of 1-(1-hydroxymethyl-2,3-dihydroxypropyl)oxymethyl-2-nitroimidazole.

Synthesis of a nitroimidazole derivative containing a 1,4-benzdioxan skeleton is characterized by having the following general formula as described in the specification. The nitroimidazole derivative containing the 1,4-benzdioxan skeleton has significant inhibition effects on human lung adenocarcinoma cell lines (A549), human cervical carcinoma cell lines (HELA), human neuroastrocytoma cell lines (U251) and human hepatoma cell lines (HEPG2), so the imidazole derivative can be applied in preparation of antitumor drugs. The invention discloses a preparation method of the nitroimidazole derivative.

It is an object to provide a method for producing a 2-nitroimidazole derivative having an acyclic sugar chain in a side chain, which is suitable for production of a derivative having a radioisotope.A method for producing 1-(1-benzoyloxymethyl-2-hydroxyethyl)oxymethyl-2-nitroimidazole, characterized by reacting glycerin with a benzoylating agent to obtain 1-O-benzoylglycerin, reacting 1-O-benzoylglycerin with dimethoxymethane in the presence of a dehydrating agent to obtain 4-benzoyloxymethyl-1,3-dioxolane, and then reacting this product with 2-nitroimidazole or 2-nitro-1-trialkylsilylimidazole in the presence of a Lewis acid.

The invention provides a nitroimidazole derivative as shown in a general formula I or a pharmaceutically acceptable salt, a solvent compound, a hydrate, a polymorphic substance, a deuterated substance and an isomer thereof. The invention also provides a pharmaceutical composition containing the compound and application of the pharmaceutical composition. The nitroimidazole derivative provided by the invention has excellent pharmacokinetic properties, and also has excellent antibacterial activity.

The invention provides a nitroimidazole derivative as shown in a general formula I or a pharmaceutically acceptable salt, a solvent compound, a hydrate, a polymorphic substance, a deuterated substance and an isomer thereof. The invention also provides a pharmaceutical composition containing the compound and application of the pharmaceutical composition. The nitroimidazole derivative provided by the invention has excellent pharmacokinetic properties, and also has excellent antibacterial activity.

The invention relates to a novel nitroimidazole compound as well as a preparation method and application of the novel nitroimidazole compound to medical science and specifically relates to a nitroimidazole compound as shown in a general formula (I), a preparation method of the nitroimidazole compound and a pharmaceutical composition containing the compound. The invention aims at synthesizing a novel compound of a series of nitroimidazole derivatives by modifying the structure of a nitroimidazole compound, the compound can be used for obviously reducing adverse reaction in clinic, meanwhile, the compound has a relatively ideal effect on protecting the liver and kidneys, and the clinical application of the compound is apparent.

The invention provides a nitroimidazole derivative for preparing a hypoxic developer. The nitroimidazole derivative is selected from compounds with structural formulas as shown in a formula I, a formula II or a formula III, wherein R is C1-8 alkyl, saturated alkoxy or acylamino. The invention also provides a preparation method of the nitroimidazole compound and application of the nitroimidazole compound in preparation of a PET imaging agent. The nitroimidazole derivative provided by the invention has proper molecular weight and fat solubility, greatly improves the ability of an imaging agent to cross a blood brain barrier, and has higher sensitivity to hypoxia due to introduction of an azide hypoxia response group.

To provide a pharmaceutical composition containing a 2-nitroimidazole derivative, which has high solubility in an aqueous carrier and high stability.The pharmaceutical composition is characterized by containing 1-(1-hydroxymethyl-2,3-dihydroxypropyl)oxymethyl-2-nitroimidazole and creatinine, and containing creatinine of 0.001 to 1 part by mass with respect to 1 part by mass of 1-(1-hydroxymethyl-2,3-dihydroxypropyl)oxymethyl-2-nitroimidazole.

An improved process for preparing 2-chloro-4-nitroimidazole derivatives which are useful intermediates in the preparation of an anti-tuberculosis drug is provided. The process may comprise the step of chlorinating nitroimidazoles with a chlorinating agent and an activating agent to give 2-chloro-4-nitroimidazole derivatives.

The invention provides a nitroimidazole derivative. The structural formula of the nitroimidazole derivative is shown as a formula I, wherein R1 is any one selected from H or C1-8 alkyl, saturated alkoxy or amido, R5 is selected from C1-8 alkyl, saturated alkoxy or amido, a substituent group is selected from-(CH2) n and-(OCH2CH2) n-, and n is an integer of 1-4; R2 is selected from C1-8 alkyl, saturated alkoxy or acylamino, a substituent group is selected from any one of -(CH2) n and-(OCH2CH2) n-, and n is an integer of 1-4; R3 is selected from -(CH2) m and-(CH2) m-CH-COOH, and m is an integer of 1-7. The invention also provides a preparation method and application of the nitroimidazole derivative. The nitroimidazole derivative provided by the invention improves the pharmacokinetics of the imaging agent.

The object of the present invention is to provide a novel pharmaceutical for suppressing cancer stem cells. In the present invention, a mitochondria inhibitor comprising a 2-nitroimidazole derivative is applied to the cancer stem cell as an active ingredient.

An improved process for preparing 2-chloro-4-nitroimidazole derivatives which are useful intermediates in the preparation of an anti-tuberculosis drug is provided. The process may comprise the step of chlorinating nitroimidazoles with a chlorinating agent and an activating agent to give 2-chloro-4-nitroimidazole derivatives.

The object of the present invention is to provide a novel pharmaceutical for suppressing cancer stem cells. In the present invention, a mitochondria inhibitor comprising a 2-nitroimidazole derivative is applied to the cancer stem cell as an active ingredient.

It is an object to provide a method for producing a 2-nitroimidazole derivative having an acyclic sugar chain in a side chain, which is suitable for production of a derivative having a radioisotope.A method for producing 1-(1-benzoyloxymethyl-2-hydroxyethyl)oxymethyl-2-nitroimidazole, characterized by reacting glycerin with a benzoylating agent to obtain 1-O-benzoylglycerin, reacting 1-O-benzoylglycerin with dimethoxymethane in the presence of a dehydrating agent to obtain 4-benzoyloxymethyl-1,3-dioxolane, and then reacting this product with 2-nitroimidazole or 2-nitro-1-trialkylsilylimidazole in the presence of a Lewis acid.

The present invention concerns novel carbonic anhydrase IX inhibitors comprising a nitroimidazole moiety and their use in therapy of hypoxic conditions, in particular cancer treatment, especially chemotherapy and radiotherapy. The compounds of the invention have an increased specificity for the carbonic anhydrase IX enzyme compared to the art. The present invention relates to novel nitroimidazole derivates represented by formula (1), wherein R1, R2, and Z are as defined herein:

The invention relates to an F-1,2,3-triazole ring-polyethylene glycol-metronidazole compound which has the following structural general formula: L is ethyl or polyethylene glycol with the following structure: n is equal to 0, 1, 2 or 3; M is a triazole ring with the following structure: or, N is ethyl or polyethylene glycol with the following structure; n is equal to 0, 1, 2 or 3; and A is 19F or18F. Under a changeless condition that the invention keeps the metronidazole as a targeting base group, the polyethylene glycol is introduced to modify and change the molecular structure of a medicine, and the aims of improving medicine dynamics and pharmacodynamical properties and increasing the curative effect of the medicine are achieved. The triazole ring, a PEG base group, 2- metronidazole and 18 / 19F nuclide are connected by a click method, and a series of novel F-triazole ring-PEG-metronidazole derivatives are designed and synthesized. The nitro imidazole derivatives can quicken removing from normal tissues by lowering fat solubility so as to enhance a target / non-target ratio and is used for the development research of tumours, cardiac muscles or brain anoxia.