- Nitroxide derivative of ROCK kinase inhibitor
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The invention provides a small molecular compound of a NO donor. The small molecular compound is characterized in that the small molecular compound is a compound shown represented by structural formula I shown in the description, or a stereoisomer, a geometrical isomer, a tautomer, a racemate, a deuterated isotope derivative, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof; and in the formula I, ring A is a substituted or unsubstituted heteroaromatic ring, X is selected from (CH2)n, n is selected from 0, 1, 2 and 3, R is a substituent group of terminal -O-NO2, R is selected from hydrogen, a hydroxyl group, halogen, an amino group, a cyano group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group and a substituted or unsubstituted heteroalkyl group, and R and R are respectively and independently selected from hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted naphthenic base or an amino protecting group, or R and R are connected to form a substituted or unsubstituted cyclic heteroalkyl group. The compound has a high-activity inhibition effect on ROCK kinase.
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Paragraph 0475-0481
(2020/06/17)
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- Design, synthesis and biological activity evaluation of NO donor-containing ferrocene-pyrazole derivative
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The invention discloses an NO donor-containing ferrocene-pyrazole derivative and a preparation method thereof. A structure of the NO donor-containing ferrocene-pyrazole derivative is shown by the following formula, wherein R is selected from the following groups.
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Paragraph 0031; 0039-0040
(2020/02/14)
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- Design, synthesis and biological evaluation of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy
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A series of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy were designed, synthesized and biologically evaluated. Among them, compound 7l displayed the most potent inhibitory against COX-2 (IC50 = 0.82 μM) and antiproliferative activities against Hela cells (IC50 = 0.34 μM) compared with Celecoxib (IC50 = 0.38 and 7.91 μM). The further mechanistic studies revealed that 7l could induce apoptosis of Hela cells by mitochondrial depolarization and the antiproliferative activities of 7l were positively correlated with the levels of intracellular NO release in Hela cells. Most notably, 7l could dramatically suppress tumor growth in Hela cells xenografted mouse model. In summary, compound 7l may be promising candidates for cancer therapy.
- Ren, Shen-Zhen,Wang, Zhong-Chang,Zhu, Dan,Zhu, Xiao-Hua,Shen, Fa-Qian,Wu, Song-Yu,Chen, Jin-Jin,Xu, Chen,Zhu, Hai-Liang
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p. 909 - 924
(2018/08/31)
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- Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors
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We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties.
- Biava, Mariangela,Battilocchio, Claudio,Poce, Giovanna,Alfonso, Salvatore,Consalvi, Sara,Di Capua, Angela,Calderone, Vincenzo,Martelli, Alma,Testai, Lara,Sautebin, Lidia,Rossi, Antonietta,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Giordani, Antonio,Persiani, Stefano,Colovic, Milena,Dovizio, Melania,Patrignani, Paola,Anzini, Maurizio
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p. 772 - 786
(2014/01/23)
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- 1,5-Diaryl-2-alkylpyrrole-3-Substituted Nitro Esters, Selective COX-2 Inhibitors and Nitric Oxide Donors
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1,5-diaryl-2-alkylpyrrole-3-substituted nitro esters, of Formula (I) are provided. Such compounds are potent and selective COX-2 inhibitors which are able to release NO in concentrations that make it possible to counteract the side effects due to selective COX-2 inhibition, without giving rise to hypotensive effects. Formula (I) includes compounds wherein the groups R′ and R″ are: —H, —F, —Cl, —Br, —CH3, —CF3, —OCH3, —SCH3, R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position ?3 of the pyrrole ring is a chain, where the groups X, Y, Z, W and R2 are: X is a carbonyl or a group —(CHR3)—, Y is an oxygen atom or the group —NR3— and Z is a carbonyl or a group —(CHR3)—, or a [—CH(COOH)—] group, or a group —(NR3)—, W is an aliphatic chain substituted with one or two (—O—NO2) groups, R2 is: —H, —OH, —OCH3, or —NHR3. R3 is: —H, —CH3, —CH2CH3, [—CH2(CH3)2]. R′″ is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.
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Paragraph 0244
(2013/07/05)
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- NITRATE AND DIAZENIUMDIOLATE DERIVATIVES OF PIOGLITAZONE
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Nitrate ester and diazeniumdiolate derivatives of pioglitazone are described. They have valuable properties in the treatment of vascular and metabolic diseases, for example type 2 diabetes.
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Paragraph 0065; 0066
(2013/03/28)
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- L,5-DIARYL-2-ALKVLPVRROLE-3-SUBSTITUTED NITRO ESTERS, SELECTIVE COX-2 INHIBITORS AND NITRIC OXIDE DONORS
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The present invention relates to l,5-diaryl-2-alkylpyrrole-3-substituted nitro esters, of formula (I), which are potent and selective COX-2 inhibitors able to release NO in concentrations that make it possible to counteract the side effects due to selective COX-2 inhibition, without giving rise to hypotensive effects. (I). Where the groups R' and R" are: -H, -F, -CI, -Br, -CH3, -CF3, -OCH3, -SCH3, R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position -3 of the pyrrole ring is a chain, where the groups X, Y, Z, W and R2 are: X is a carbonyl or a group -(CHR3)-, Y is an oxygen atom or the group -NR3- and Z is a carbonyl or a group - (CHR3)-, or a [-CH(COOH)-] group, or a group -(NR3)-, W is an aliphatic chain substituted with one or two (-O-NO2) groups, R2 is: -H, -OH, -OCH3, or -NHR3. R3 is: -H, -CH3, -CH2CH3, [-CH2(CH3)2]. R'" is methylsulphonyl or sulphonamido. The purpose of the invention includes: preparation of the compounds of formula (I), the respective pharmaceutical formulations and use thereof for treating acute and chronic pain, for treating inflammatory disorders and for drug treatment of some forms of tumours.
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Page/Page column 65; 66
(2012/03/27)
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- VALSARTAN DERIVATIVES CARRYING NITROGEN OXIDE DONORS FOR THE TREATMENT OF VASCULAR AND METABOLIC DISEASES
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Nitrate esters and diazeniumdiolate derivatives of valsartanamide are described. They have valuable properties in the treatment of vascular and metabolic diseases.
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Page/Page column 15-16
(2011/11/06)
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- A valsartanamide dinitrate derivative for the treatment of vascular and metabolic diseases
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A dinitrate ester of a valsartanamide is described. It has superior properties in the treatment of vascular and metabolic diseases.
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Page/Page column 9
(2011/11/01)
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- NITRATE AND DIAZENIUMDIOLATE DERIVATIVES OF PIOGLITAZONE
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Nitrate ester and diazeniumdiolate derivatives of pioglitazone are described. They have valuable properties in the treatment of vascular and metabolic diseases, for example type 2 diabetes.
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Page/Page column 14-15
(2011/12/14)
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- N'-NITROXYALKYLNICOTINAMIDES FOR THE TREATMENT OF CARDIOVASCULAR DISEASES
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The invention relates to the novel N′-nitroxyalkylnicotinamide derivatives represented by the general formula I wherein R1 is C1-C4 alkyl; R2 is hydrogen. C1-C4 alkyl, CH2OH or CH2ONO2; R3 is ONO2, CH2ONO2 or OH; provided that when R3 is OH, R2 is CH2ONO2; and X? is an organic or inorganic anion; as well as pharmaceutical compositions thereof and their use as a medicament, in particular, in the treatment of diseases of the cardiovascular system.
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Page/Page column 4
(2011/04/24)
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- Synthesis and evaluation of nitric oxide-releasing derivatives of 3-n-butylphthalide as anti-platelet agents
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Most ischemic stroke results from brain blood vessel blockage by platelet-mediated thrombus, and anti-platelet therapy has been demonstrated clinical benefits in the treatment of this disease. In the present work, novel nitric oxide (NO)-releasing derivatives of an anti-ischemic stroke drug 3-n-butylphthalide (NBP) were synthesized. Compounds 7a and 7c exhibited more potent anti-platelet activity than NBP and aspirin, and released a moderate amount of NO, which is beneficial in improving cardiovascular and cerebral circulation. These findings provide an alternative approach to the development of drugs more potent than NBP for the intervention of ischemic stroke.
- Li, Yang,Wang, Xuliang,Fu, Rong,Yu, Wenying,Wang, Xiaoli,Lai, Yisheng,Peng, Sixun,Zhang, Yihua
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scheme or table
p. 4210 - 4214
(2011/08/06)
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- N'-NITROXYALKYLNICOTINAMIDES FOR THE TREATMENT OF CARDIOVASCULAR DISEASES
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The invention relates to the novel N'-nitroxyalkylnicotinamide derivatives represented by the general formula (I) wherein R1 is C1C4 alkyl; R2 is hydrogen, C1-C4 alkyl, CH2OH or CH2ONO2; R3 is ONO2, CH2ONO2 or OH; provided that when R3 is OH, R2 is CH2ONO2; and X- is an organic or inorganic anion; as well as pharmaceutical compositions thereof and their use as a medicament, in particular, in the treatment of diseases of the cardiovascular system.
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Page/Page column 11
(2010/04/03)
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- Nitroanandamide, nitroprostamides E2 and F2α', and their analogs
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Synthetic methods were developed for nitrates of the natural bioactive lipids anandamide and prostamides E2 and F2α in addition to their analogs that contained nitrates of ethanolamine and 3-amino-1,2-propanediol as the NO-generating fragment.
- Serkov,Gretskaya,Bezuglov
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body text
p. 696 - 700
(2011/03/21)
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- Nitric oxide enhancing diuretic compounds, compositions and methods of use
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The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.
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Page/Page column 37
(2008/06/13)
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- Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: Nitric oxide-donor naproxen prodrugs
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A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b,
- Ranatunge, Ramani R.,Augustyniak, Michael E.,Dhawan, Vijay,Ellis, James L.,Garvey, David S.,Janero, David R.,Letts, L. Gordon,Richardson, Stewart K.,Shumway, Mathew J.,Trocha, A. Mark,Young, Delano V.,Zemtseva, Irina S.
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p. 2589 - 2599
(2007/10/03)
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- Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use related applications
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The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
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Page/Page column 38; 39
(2010/11/30)
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- Synthesis of nitroxyalkylammonium nitrates
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A method for O-nitration of amino alohols with a non-detonating mixture of nitric acid with dichloromethane has been proposed.The target crystalline products were precipitated from the reaction mixture by acetic anhydride. - Key words: nitroxyalkylammonium nitrates; amino alcohols; O-nitration; concentration limits of detonation; explosion-proof process.
- Romanova, L. B.,Ivanova, M. E.,Nesterenko, D. A.,Eremenko, L. T.
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p. 1207 - 1208
(2007/10/02)
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