- Mussel-inspired healing of a strong and stiff polymer
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Self-healability will greatly improve the reliability, service life and maintenance of synthetic materials. However, it remains a big challenge to realize the self-healing of a strong and stiff polymer due to its poor molecular mobility. Inspired by the h
- Chen, Ning,Qin, Liming,Pan, Qinmin
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Read Online
- Photodegradable self-assembling PAMAM dendrons for gene delivery involving dendriplex formation and phototriggered circular DNA release
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For effective gene delivery, structural degradation of synthetic carriers is crucial to the release of nucleic acids on the transfection time scale. In this study, we have synthesized the amphiphilic dendritic scaffolds with a photolabile o-nitrobenzyl (o-NB) group that can enable the structural decomposition and controlled release of nucleic acids under active light stimulation. The amphiphilic counterpart composed of a lipophilic cholesterol and a hydrophilic poly(amido amine) (PAMAM) dendron allows the self-assembly into a core-shell-like pseudodendrimer above the critical aggregation concentration (CAC) of approximately 20 μM. On the basis of electrostatic interaction, the polycationic pseudodendrimers are capable of forming stable complexes with polyanionic cyclic reporter genes under low charge excess values, suggesting substantial binding affinity of the dendron assembly toward circular DNA. Because the o-NB group in the dendritic structure undergoes efficient photolytic cleavage, an in vitro test shows that thus-formed "dendriplexes" are readily dissociated under 365 nm light irradiation, causing effective dendron degradation accompanied by DNA release. This photochemical strategy provides an opportunity to control gene binding and release in a spatiotemporal manner.
- Lai, Yu-Sen,Kao, Chai-Lin,Chen, Ya-Pei,Fang, Chia-Chia,Hu, Chao-Chin,Chu, Chih-Chien
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- Synthesis and in-vitro anti-hepatitis-B virus activity of 6H-[1]benzothiopyrano[4,3-b] quinolin-10-ols
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A series of 9-methoxy-6H-[1]benzothiopyrano[4,3-b]quinolin-10-ols with a Mannich side chain were synthesized and evaluated for their anti-Hepatitis B virus (HBV) activity in HepG2.2.15 cells. Some compounds showed significant anti-HBV activity with IC50 values less than 41 μM. Among them, compound 9b was the most effective anti-HBV agent (IC50 = 1.7 μM, SI = 60.3).
- Jia, Wei,Zhao, Yanfang,Li, Rongdong,Wu, Yanjiao,Li, Zebiao,Gong, Ping
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Read Online
- Phototriggered labeling and crosslinking by 2-nitrobenzyl alcohol derivatives with amine selectivity
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Here we report the use of 2-nitrobenzyl alcohol (NB) as a photoreactive group with amine selectivity and explore its applications for photoaffinity labeling and crosslinking of biomolecules. This work confirms that NB is an efficient photoreactive group a
- Wang, Chenxi,Liu, Yuan,Bao, Chunyan,Xue, Yuan,Zhou, Yaowu,Zhang, Dasheng,Lin, Qiuning,Zhu, Linyong
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p. 2264 - 2267
(2020/03/04)
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- G-A CROSSLINKING CYTOTOXIC AGENTS
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The invention relates to a compound of formula (I): or salts, solvates, isomers or tautomers thereof, wherein; A is a group selected from: R1 is selected from H and halogen; either R2 is selected from -CH2-halogen, C1
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- POLYCYCLIC AMIDES AS CYTOTOXIC AGENTS
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The invention relates to a compound of formula (I): or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; wherein the fused ring moiety is a non-alkylating moiety; and wherein the compounds are useful as medicaments, in particular for use as a drug in an antibody-drug conjugate and in the treatment of a proliferative disease, a bacterial infection, a malarial infection and inflammation.
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- Preparation method of disulfide bond-containing dual-response functional molecule and hydrogel microsphere and application thereof
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The invention discloses a disulfide bond-containing dual-response functional molecule, and the structural general formula of the disulfide bond-containing dual-response functional molecule is shown inthe specification. The invention also provides the dual
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- Synthesis and biological evaluation of a novel C8-pyrrolobenzodiazepine (PBD) adenosine conjugate. A study on the role of the PBD ring in the biological activity of PBD-conjugates
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Here we sought to evaluate the contribution of the PBD unit to the biological activity of PBD-conjugates and, to this end, an adenosine nucleoside was attached to the PBD A-ring C8 position. A convergent approach was successfully adopted for the synthesis of a novel C8-linked pyrrolo(2,1-c)(1,4)benzodiazepine(PBD)-adenosine(ADN) hybrid. The PBD and adenosine (ADN) moieties were synthesized separately and then linked through a pentynyl linker. To our knowledge, this is the first report of a PBD connected to a nucleoside. Surprisingly, the compound showed no cytotoxicity against murine cells and was inactive against Mycobacterium aurum and M. bovis strains and did not bind to guanine-containing DNA sequences, as shown by DNase I footprinting experiments. Molecular dynamics simulations revealed that the PBD-ADN conjugate was poorly accommodated in the DNA minor groove of two DNA sequences containing the AGA-PBD binding motif, with the adenosine moiety of the ligand preventing the covalent binding of the PBD unit to the guanine amino group of the DNA duplex. These interesting findings shed further light on the ability of the substituents attached at the C8 position of PBDs to affect and modulate the biological and biophysical properties of PBD hybrids.
- Bhakta, Sanjib,Brucoli, Federico,Ferguson, Lindsay,Fox, Keith R.,Wells, Geoff
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- CYTOTOXIC AGENTS
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The invention relates to a compound of formula (I) or formula (II) or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; which are useful as medicaments, in particular as anti-proliferative agents and for use as a d
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- Preparation method, raw material, product and application of photo-crosslinking hydrogel material
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The invention provides a preparation method, a raw material, a product and an application of a photo-crosslinking hydrogel material. The preparation method comprises the steps of dissolving a component A, namely a photosensitive high polymer derivative, i
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- Photoresponsive multifunctional chemical crosslinking agent and preparation method and application thereof
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The invention discloses a photoresponsive multifunctional chemical crosslinking agent. The structure of the crosslinking agent is shown in a formula I, wherein the definition of each substituent groupin the formula I is shown in the description. The prepa
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- Rapid and reversible hydrazone bioconjugation in cells without the use of extraneous catalysts
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The amenability of hydrazone linkages to disassemble via either hydrolysis in mildly acidic aqueous solutions or transimination upon treatment with amine nucleophiles renders them extremely attractive for applications in chemical biology, drug delivery and materials science. Unfortunately, however, the use of hydrazones is hampered by the extremely slow intrinsic rates of their formation from their hydrazine and carbonyl precursors. Consequently, hydrazone formation is typically performed in the presence of a large excess of cytotoxic aniline-based nucleophilic catalysts, rendering hydrazones unsuitable for biological applications that entail their formation in cells. Herein, we report a hydrazine scaffold - o-amino benzyl hydrazine - that rapidly forms hydrazones via intramolecular nucleophilic catalysis, thereby obviating the use of extraneous catalysts. We demonstrate the use of this scaffold for rapid and reversible peptide and protein hydrazone bioconjugation and also for reversible fluorescent labeling of sialylated glycoproteins and choline lipids in mammalian cells.
- Nisal, Rahul,Jose, Gregor,Shanbhag, Chitra,Kalia, Jeet
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p. 4304 - 4310
(2018/06/22)
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- Nitration Using Fuming HNO3 in Sulfolane: Synthesis of 6-Nitrovanillin in Flow Mode
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We report herein an improved synthesis of 6-nitrovanillin, an important building block used in pharmaceuticals and agrochemicals. The key step in this sequence is the nitration of O-Bn vanillin, which was carried out using fuming HNO3. Sulfolan
- Rakshit, Souvik,Lakshminarasimhan, Thirumalai,Guturi, Sivakrishna,Kanagavel, Kishorekumar,Kanusu, Umamaheswara Rao,Niyogi, Ankita G.,Sidar, Somprabha,Luzung, Michael R.,Schmidt, Michael A.,Zheng, Bin,Eastgate, Martin D.,Vaidyanathan, Rajappa
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p. 391 - 398
(2018/03/22)
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- C8-Linked Pyrrolobenzodiazepine Monomers with Inverted Building Blocks Show Selective Activity against Multidrug Resistant Gram-Positive Bacteria
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Antimicrobial resistance has become a major global concern. Development of novel antimicrobial agents for the treatment of infections caused by multidrug resistant (MDR) pathogens is an urgent priority. Pyrrolobenzodiazepines (PBDs) are a promising class of antibacterial agents initially discovered and isolated from natural sources. Recently, C8-linked PBD biaryl conjugates have been shown to be active against some MDR Gram-positive strains. To explore the role of building block orientations on antibacterial activity and obtain structure activity relationship (SAR) information, four novel structures were synthesized in which the building blocks of previously reported compounds were inverted, and their antibacterial activity was studied. The compounds showed minimum inhibitory concentrations (MICs) in the range of 0.125-32 μg/mL against MDR Gram-positive strains with a bactericidal mode of action. The results showed that a single inversion of amide bonds reduces the activity while the double inversion restores the activity against MDR pathogens. All inverted compounds did not stabilize DNA and lacked eukaryotic toxicity. The compounds inhibit DNA gyrase in vitro, and the most potent compound was equally active against both wild-Type and mutant DNA gyrase in a biochemical assay. The observed activity of the compounds against methicillin resistant S. aureus (MRSA) strains with equivalent gyrase mutations is consistent with gyrase inhibition being the mechanism of action in vivo, although this has not been definitively confirmed in whole cells. This conclusion is supported by a molecular modeling study showing interaction of the compounds with wild-Type and mutant gyrases. This study provides important SAR information about this new class of antibacterial agents.
- Andriollo, Paolo,Hind, Charlotte K.,Picconi, Pietro,Nahar, Kazi S.,Jamshidi, Shirin,Varsha, Amrit,Clifford, Melanie,Sutton, J. Mark,Rahman, Khondaker Miraz
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p. 158 - 174
(2018/02/14)
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- Scale-up Synthesis of Tesirine
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This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody-drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody-drug conjugates in multiple clinical trials, four of them pivotal.
- Tiberghien, Arnaud C.,Von Bulow, Christina,Barry, Conor,Ge, Huajun,Noti, Christian,Collet Leiris, Florence,McCormick, Marc,Howard, Philip W.,Parker, Jeremy S.
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p. 1241 - 1256
(2018/09/06)
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- Method for covalently immobilizing bioactive factor by material surface/interface photo-produced aldehyde/ketone group
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The invention relates to a method for immobilizing a bioactive factor by a material surface/interface photo-produced aldehyde/ketone group in a controllable mode. The method is characterized in that ato-be-immobilized bioactive factor does not need extra
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- Reversible Control of Protein Localization in Living Cells Using a Photocaged-Photocleavable Chemical Dimerizer
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Many dynamic biological processes are regulated by protein-protein interactions and protein localization. Experimental techniques to probe such processes with temporal and spatial precision include photoactivatable proteins and chemically induced dimerization (CID) of proteins. CID has been used to study several cellular events, especially cell signaling networks, which are often reversible. However, chemical dimerizers that can be both rapidly activated and deactivated with high spatiotemporal resolution are currently limited. Herein, we present a novel chemical inducer of protein dimerization that can be rapidly turned on and off using single pulses of light at two orthogonal wavelengths. We demonstrate the utility of this molecule by controlling peroxisome transport and mitotic checkpoint signaling in living cells. Our system highlights and enhances the spatiotemporal control offered by CID. This tool addresses biological questions on subcellular levels by controlling protein-protein interactions.
- Aonbangkhen, Chanat,Zhang, Huaiying,Wu, Daniel Z.,Lampson, Michael A.,Chenoweth, David M.
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supporting information
p. 11926 - 11930
(2018/09/25)
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- ASYMMETRIC CONJUGATE COMPOUNDS
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The invention relates to compound of formula (I): A-X1-L-X2-B and salts, solvates and tautomers thereof, which are useful as medicaments, in particular as anti-proliferative agents and for use as a drug in an antibody-drug conjugate;
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- QUINUCLIDINES FOR MODULATING ALPHA 7 ACTIVITY
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Provided are substituted quinuclidine compounds, pharmaceutical compositions comprising such compounds, and methods of modulating α7 nicotinic acetylcholine receptors and treating neurological disorders using such compounds.
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- Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload
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Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity a
- Tiberghien, Arnaud C.,Levy, Jean-Noel,Masterson, Luke A.,Patel, Neki V.,Adams, Lauren R.,Corbett, Simon,Williams, David G.,Hartley, John A.,Howard, Philip W.
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supporting information
p. 983 - 987
(2016/11/19)
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- COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
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- Controlled proliferation and screening of mammalian cells on a hydrogel-functionalized small molecule microarray
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A hydrogel-functionalized small molecule microarray has been developed, on which PC-3 cancer cells were selectively grown. Subsequent controlled release of immobilized bioactive compounds enabled cell-based screening to be directly carried out on this pla
- Zhu, Biwei,Jiang, Bo,Na, Zhenkun,Yao, Shao Q.
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p. 10431 - 10434
(2015/06/25)
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- COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
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- QUINOLINE OR QUINAZOLINE DERIVATIVES WITH APOPTOSIS INDUCING ACTIVITY ON CELLS
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Provided is a pharmaceutical composition comprising, as an active ingredient, a quinoline or quinazoline derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate, and a solvate thereof, which is effective in the prevention and treatment of a cancer, inflammation, autoimmune diseases or neurodegenerative disorders which are induced by the overexpression of inhibitor of apoptosis proteins (IAPs).
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Page/Page column 50
(2012/03/26)
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- SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS
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Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease.
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Page/Page column 48
(2012/07/28)
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- (AZA)INDOLE DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES
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The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level which has a uricosuric activity or the like. The present invention relates to (aza)indole derivatives represented by the following general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro or cyano and the like; ring J represents aryl or heteroaryl and the like; Q represents carboxy or 5-tetazolyl and the like; Y represents H, OH, NH2, halogen, nitro, alkyl, alkoxy and the like; X1, X2 and X3 independently represent CR2 or N; R1 and R2 independently represent halogen, cyano, haloalkyl, A-D-E-G, -N(-D-E-G)2 and the like, in the formula, A represents a single bond, O, S and the like; D and G independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E represents a single bond, O, S, COO, SO2 and the like.
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Page/Page column 28-29
(2009/12/27)
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- Synthesis and anti-HBV activities evaluation of new ethyl 8-imidazolylmethyl-7-hydroxyquinoline-3-carboxylate derivatives in vitro
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Some new ethyl 8-imidazolylmethyl-7-hydroxyquinoline-3-carboxylate derivatives have been synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in HepG2.2.15 cells stable transfection with HBV. Compounds 13a, 11b, 11c, 12c, 13c, 11g, and 12g inhibited the expression of the viral antigens HBsAg or HBeAg in a low concentration, of which 11c (IC50 = 12.6 μM, SI = 12.4), 12c (IC50 = 3.5 μM, SI = 37.9), and 12g (IC50 = 2.6 μM, SI = 61.6) showed more active abilities to inhibit the replication of HBV DNA than the positive control lamivudine (3TC, IC50 = 343.2 μM, SI = 7.0).
- Liu, Yajing,Zhao, Yanfang,Zhai, Xin,Liu, Xiuping,Sun, Lixue,Ren, Yanxia,Gong, Ping
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body text
p. 446 - 452
(2009/04/11)
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- Syntheses of NAMDA derivatives inhibiting NO production in BV-2 cells stimulated with lipopolysaccharide
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Sixteen derivatives of N-acetyl-3-O-methyldopamine (NAMDA), an inhibitor of BH4 synthesis, were designed and synthesized. The ability of these derivatives to inhibit NO and BH4 production by lipopolysaccharide- stimulated BV-2 microglial cells was determined. While NAMDA at 100 μM inhibited NO and BH4 production by only about 20%, its catecholamide 8, indole 23 derivative, 13, and N-acetyl tetrahydroisoquinoline 25 inhibited the NO production by >50% at the same concentration. In particular, 13 and 25 inhibited both NO and BH4 production to similar degrees, which suggested that these compounds might inhibit NO production by blocking BH 4-dependent dimerization of the newly synthesized iNOS monomer.
- Jai, Woong Seo,Srisook, Ekaruth,Hyo, Jin Son,Hwang, Onyou,Cha, Young-Nam,Dae, Yoon Chi
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p. 3369 - 3373
(2007/10/03)
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- De Novo design and utilization of photolabile caged substrates as probes of hydrogen tunneling with horse liver alcohol dehydrogenase at sub-zero temperatures: A cautionary note
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In order to understand the influence of protein dynamics on enzyme catalysis and hydrogen tunneling, the horse liver alcohol dehydrogenase (HLADH) catalyzed oxidation of benzyl alcohol was studied at sub-zero temperatures. Previous work showed that wild t
- Tsai, Shiou-Chuan,Klinman, Judith P.
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p. 172 - 190
(2007/10/03)
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- Benzyltriphenylphosphonium Peroxodisulfate (PhCH2PPh3)2S2O8: A Mild and Inexpensive Reagent for Efficient Oxidation of Organic Compounds under Nonaqueous and Aprotic Conditions
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Benzyltriphenylphosphonium peroxodisulfate is an easily prepared and stable reagent. It could be used as an oxidant under aprotic and nonaqueous conditions in organic solvents. This reagent oxidizes different classes of alcohols to carbonyl compounds, thiols to disulfides, sulfides to sulfoxides, oximes to carbonyl compounds and aromatic amines to azo compounds efficiently. α-Hydroxy carboxylic acids and phenylacetic acids undergo oxidative decarboxylation to produce carbonyl compounds.
- Mohammadpoor-Baltork, Iraj,Hajipour, Abdol Reza,Mohammadi, Hasan
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p. 1649 - 1653
(2007/10/03)
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- Tetrakis(pyridine)silver(II) Peroxodisulfate, S2O8, a Reagent for the Oxidative Transformations
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Tetrakis(pyridine)silver(II) peroxodisulfate oxidizes aromatic aldehydes to carboxylic acids, benzylic alcohols to carbonyl compounds, aromatic thiols, and allylaryl thioethers to arylsulfonic acids and benzylic carbon-hydrogen bonds to carbonyl groups. α-Hydroxycarboxylic acids and phenylacetic acids are decarboxylated to produce carbonyl compounds.Dibenzyl ether and its sulfur analogue are converted to their corresponding ester and the thioester, respectively.
- Firouzabadi, Habib,Salehi, Peyman,Mohammadpour-Baltork, Iraj
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p. 2878 - 2880
(2007/10/02)
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- Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a method for allergy treatment
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A method of inhibiting Type 1 allergic responses in a living animal body with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain known compounds: STR1 wherein P is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, CH2 -- or STR2 n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the α carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one,4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one, 1,4-benzodioxanloweralkyl-2-yl or 1,1'-biphenyl-4-yl and the pharmaceutically acceptable salts thereof.
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- Improved Synthesis of 6-Hydroxy-5-methoxy- and 5-Hydroxy-6-methoxyindoles and Their O-Acetates, Analogs of Natural Eumelanin Precursors.
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Improved routes for syntheses of gram quantities of the isomeric 5,6-acetoxymethoxyindoles, and milligram amounts of the 5,6-hydroxymethoxyindoles, have been developed.They depend on regiospecific nitration of the benzyl ethers of vanillin and isovanillin
- Rogers, C. Bradford,Blum, Charles A.,Murphy, Bryan P.
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p. 941 - 943
(2007/10/02)
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- Cleavage of the Methylenedioxy Ring. III. Cleavage with Sodium Benzyloxide in Dimethyl Sulfoxide
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Cleavage of the methylenedioxy ring in aromatic formyl (1-3), nitro (4 and 5), and acetyl (30) compounds with N-sodium benzyloxide-benzyl alcohol in dimethyl sulfoxide gave 3-hydroxybenzene derivatives (19, 22-24, 26, 27, and 33).In the case of the acetyl compound 30, the 4-hydroxybenzene derivative (34) was also obtained as a minor product.Regioselective cleavage of the ring in aromatic compounds having electronwithdrawing groups with nucleophilic oxide anions is discussed.Cleavage of the ring in 1-5 and 30 with 2 N sodium methoxide in dimethyl sulfoxide-dimethylformamide was found to be useful for the practical preparation of 3-hydroxybenzene derivatives (6-10 and 31).Keywords - Cleavage of methylenedioxy ring; regioselectivity; piperonals; 3,4-methylenedioxy-nitrobenzene; 3,4-methylenedioxy-acetophenone; sodium methoxide; sodium phenoxide; sodium benzyloxide; dimethyl sulfoxide; dimethylformamide
- Kobayashi, Shigeru,Okimoto, Kazuto,Imakura, Yasuhiro
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p. 1567 - 1573
(2007/10/02)
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- Synthesis and identification of the major metabolites of prazosin formed in dog and rat
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The 6 O demethyl and 7 O demethyl analogues of the new antihypertensive drug prazosin [2 [4 (2 furoyl) piperazin 1 yl] 4 amino 6,7 dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate ten step reaction sequences starting from isovanillin and vanillin, respectively. The 6 O demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7 O demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2 (1 piperazinyl) 4 amino 6,7 dimethoxyquinazoline and 2,4 diamino 6,7 dimethoxyquinazoline, are also described. All four metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.
- Althuis,Hess
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p. 146 - 149
(2007/10/05)
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