- CHLORINE-ISOTOPIC EXCHANGE BETWEEN LITHIUM CHLORIDE AND SUBSTITUTED 2-CHLOROPYRIDINE IN HOMOGENEOUS SOLUTION
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The kinetics of chlorine-isotopic exchange between lithium chloride-36 and cyano- and nitro-substituted 2-chloropyridines were measured in sulpholane, acetone or methanol solution.Activating effects of ortho-nitro and ortho-azu substitution are compared: a nitro-group is 50 x as activating as the aza-group in the p-nitrochlorobenzene system, whereas it is the aza-function which is 3 times as activiting as the nitro group in the o-nitrochlorobenzene system.The effect of Me substituents placed ortho to an activating nitro-group was studied by comparing 2-chloro-3-cyano-5-nitropyridine and its 6-methyl- and 4,6-dimethyl derivatives.
- Gore, Peter H.,Hundal, Apparapar S.,Morris, Donald F. C.
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Read Online
- Hydrophobic metallo-supramolecular Pd2L4 cages for zwitterionic guest encapsulation in organic solvents
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Hydrophilic zwitterionic guest encapsulation by metallo-supramolecular cages through synergetic coordination, H-bonding and hydrophobic interactions.
- Li, Yu-Hao,Zhang, Yan,Legrand, Yves-Marie,Van Der Lee, Arie,Jiang, Ji-Jun,Chen, Cheng-Xia,Su, Cheng-Yong,Barboiu, Mihail
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Read Online
- Synthetic method of active intermediate 4-chloro-3-nitropyridine
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The invention discloses a synthetic method of active intermediate 4-chloro-3-nitropyridine. The method comprises the following steps: step 1, adding 24L of concentrated sulfuric acid into a 50L reaction kettle, cooling to about 10 DEG C, adding 4kg of raw materials in batches, carrying out HPLC detection on the end of the reaction of the raw materials on the next day, carrying out aftertreatment, slowly pouring the reaction liquid into 30L of ice water for quenching, adjusting the pH value to 7, carrying out suction filtration to obtain a faint yellow solid, and carrying out suction filtration; drying to obtain 4.6 kg of 4-hydroxy-3-nitropyridine faint yellow solid with the yield of 80% and the purity of 98%; and 2, adding 500g of SM into a 10L reaction flask at room temperature, dissolving with 5L of methylbenzene, dropwise adding 1643g of phosphorus oxychloride at room temperature, dropwise adding the crude product into PE, stirring and extracting for multiple times to obtain 388g of 4-chloro-3-nitropyridine faint yellow solid with the yield of 68% and the purity of 95%. According to the synthetic method of active intermediate 4-chloro-3-nitropyridine, improvement points of the project process mainly aim at purity control and reaction stability control of the reaction in the third step, aftertreatment is simple, and product purification can be achieved through extraction.
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Paragraph 0013; 0019; 0025
(2021/04/28)
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- METHOD FOR PREPARING HETEROCYCLIC DERIVATIVE COMPOUND, COMPOSITION CONTAINING SAME COMPOUND, AND HYDRATE OF SAME COMPOUND
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The present invention relates to: a novel method for preparing a heterocyclic derivative compound of chemical formula I below; a novel intermediate compound used in the preparation method; a composition for treatment or prevention of hyperuricacidemia, gout, nephritis, chronic renal insufficiency, nephrolith, uremia, urolithiasis, or a uric acid-related disease, the composition containing the compound of chemical formula I at a dose of more than 2 mg and equal to or less than 10 mg and being orally administered once a day; and a hydrochloride 1.5 hydrate of the novel compound of chemical formula I.
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Paragraph 0097
(2020/04/21)
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- NOVEL AROMATIC COMPOUND AND USE THEREOF
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Provided is a compound showing a bone formation promoting action (and/or bone resorption suppressive action). A compound of the formula (I) or a pharmacologically acceptable salt: [wherein each substituent is as defined in the DESCRIPTION], has low toxicity, shows good pharmacokinetics, has an action to promote bone formation, and is useful for the prophylaxis or To treatment of metabolic bone diseases (osteoporosis, fibrous osteitis (hyperparathyroidism), osteomalacia, Paget's disease that influences the systemic bone metabolism parameter etc.) associated with a decrease in the bone formation ability as compared to the bone resorption capacity.
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Paragraph 0330-0332
(2016/08/17)
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- 4-chloro-3-nitropyridine and preparation method thereof
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The invention discloses 4-chloro-3-nitropyridine and a preparation method thereof. The preparation method is characterized in that 4-hydroxypyridine is taken as the raw material, ionic liquid is taken as a reaction medium and mesoporous silica is taken as a catalyst, and comprises the following steps: firstly, carrying out nitration reaction with nitric acid to produce 4-hydroxyl-3-nitropyridine; carrying out reaction between 4-hydroxyl-3-nitropyridine and phosphorus oxychloride under catalyzation of thionyl chloride to produce 4-chloro-3-nitropyridine. According to 4-chloro-3-nitropyridine and the preparation method thereof provided by the invention, the condition is mild and easy to control, the requirement on equipment is low, the product purity is high, and the yield is high.
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Paragraph 0019; 0022
(2016/11/17)
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- High colour rendering index and colour stable hybrid white efficient OLEDs with a double emitting layer structure using a single phosphorescence dopant of heteroleptic platinum complexes
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Four heteroleptic platinum complexes (FPtXND) bearing 4-hydroxy-1,5-naphthyridine derivatives functionalized with dimethyl (X = mm), phenoxy (X = OPh), piperidine (X = pp), or carbazole (X = Cz) units as one ligand (XND) and 2-(2,4-difluorophenyl)pyridine as the other common ligand (F) were newly synthesized and characterized. The crystal structures of FPtOPhND and FPtCzND were determined by single-crystal X-ray diffraction crystallography. Although they have a short plane-to-plane packing distance of 3.62 and 3.39 A, respectively, both platinum complexes have different molecular packing patterns, which affect their photoluminescence (PL) in solution and electroluminescence (EL) in the solid state. Due to the contribution from both monomers and excimers/aggregates, all of the platinum complexes exhibited broad and red-shifted PL in concentrated solutions as well as in doped thin films. In the monochromatic organic lighting diode (OLED) testing, FPtXND doped in 4,4′-di(9H-carbazol-9-yl)-1,1′-biphenyl (CBP) exhibited greenish yellow or orange yellow EL, of which FPtOPhND has the highest EL efficiency mainly due to its high solution PL quantum yield of 21%. Hybrid white OLEDs were first achieved with a single emitting layer configuration, of which highly fluorescent blue N,N′-di-1-naphthalenyl-N,N′-diphenyl-[1,1′:4′,1″:4″,1-quaterphenyl]-4,4-diamine (4P-NPD) was used as the host material for all four platinum complexes. To improve the performance of the FPtOPhND-based hybrid white OLEDs, double emitting layer configurations were adopted with CBP and 4P-NPD as the host material. Virtually voltage independent, a white EL having CIEx,y (0.33, 0.31) and a CRI as high as 91 was obtained. The maximum EL efficiency of 11.8%, 25.9 cd A-1, or 11.6 lm W-1 was acquired with FPtOPhND doped in the double emitting layer configuration of an OLED.
- Poloek, Anurachw,Lin, Chiao-Wen,Chen, Chin-Ti,Chen, Chao-Tsen
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p. 10343 - 10356
(2015/02/19)
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- AMINE COMPOUNDS HAVING ANTI-INFLAMMATORY, ANTIFUNGAL, ANTIPARASITIC AND ANTICANCER ACTIVITY
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Amine compounds having activity against inflammation, fungi, unicellular parasitic microorganisms, and cancer are described. The compounds contain a monocyclic, bicyclic, or tricyclic aromatic ring having one, two, or three ring nitrogen atoms.
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Page/Page column 189
(2014/08/19)
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- Use of the graebe-ullmann reaction in the synthesis of 8-methyl-γ- carboline and isomeric aromatic aza-γ-carbolines
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Two variants of the Graebe-Ullmann reaction were used to obtain 8-methyl-5H-pyrido[4,3-b]indole (8-methyl-γ-carboline) and the conditions for this reaction were optimized. The feasibility of using this method was studied for the synthesis of a series of isomeric aromatic aza-γ- carbolines from the corresponding 1-(pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridines under thermal and microwave irradiation conditions.
- Alekseev,Kurkin,Yurovskaya
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p. 1235 - 1250
(2013/03/13)
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- Preparation of azaindolines and benzoyl substituted azaindolines: Precursors of triazabenzo[cd]azulen-9-one PDE4 inhibitors
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The syntheses of various substituted azaindolines are described. Azaindolines were identified as potential key intermediates towards new PDE4 inhibitors.
- Badland, Matthew,Devillers, Ingrid,Durand, Corinne,Fasquelle, Véronique,Gaudillire, Bernard,Jacobelli, Henry,Manage, Ajith C.,Pevet, Isabelle,Puaud, Jocelyne,Shorter, Anthony J.,Wrigglesworth, Roger
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supporting information; experimental part
p. 5292 - 5296
(2011/10/30)
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- LONIDAMINE ANALOGUES FOR FERTILITY MANAGEMENT
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Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject.
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Page/Page column 68
(2011/02/24)
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- A novel one-pot palladium-mediated synthesis of N-[(2-hydroxyphenyl)methyl]-N-(4-phenoxy-3-pyridinyl) acetamide, the precursor to [11C]PBR28, a PET biomarker for the peripheral benzodiazepine receptor
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Due to an urgent need to image the peripheral benzodiazepine receptor (PBR) in living human subjects using positron emission tomography imaging, we had cause to prepare N-[(2-hydroxyphenyl)methyl]-N-(4-phenoxy-3-pyridinyl) acetamide (desmethyl-PBR28 (1)), the precursor to [11C]PBR28. Herein, we report a new synthesis of the precursor in which palladium-mediated reduction of the nitro pyridine to the corresponding amino pyridine, and subsequent reductive amination, can be achieved with decaborane in a convenient one-pot procedure. This procedure is operationally simpler than the current alternatives and provides high quality precursor suitable for use in clinical applications.
- Hoareau, Rapha?l,Scott, Peter J.H.
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scheme or table
p. 3353 - 3355
(2010/09/05)
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- Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo
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We sought to develop 11C-labeled ligands for sensitive imaging of brain peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high affinity for PBR were identified and synthesized, namely, N-acetyl-N-(2-methoxycarbonylbenzyl)-2-phenoxyaniline (3, PBR01) and N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide (10, PBR28). 3 was hydrolyzed to 4, which was esterified with [11C]iodomethane to provide [11C]3. The O-desmethyl analogue of 10 was converted into [11C]10 with [11C]iodomethane. [11C]3 and [11C]10 were each injected into monkey to assess their brain kinetics with positron emission tomography (PET). After administration of either radioligand there was moderately high brain uptake of radioactivity. Receptor blocking and displacement experiments showed that a high proportion of this radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each to a single polar radiometabolite. [11C]3 and [11C]10 are effective for imaging PBR in monkey brain. [11C]10 especially warrants further evaluation in human subjects.
- Briard, Emmanuelle,Zoghbi, Sami S.,Imaizumi, Masao,Gourley, Jonathan P.,Shetty, H. Umesha,Hong, Jinsoo,Cropley, Vanessa,Fujita, Masahiro,Innis, Robert B.,Pike, Victor W.
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- Discovery of aminofurazan-azabenzimidazoles as inhibitors of rho-kinase with high kinase selectivity and antihypertensive activity
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The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension. Despite many available treatments, hypertension remains a prevalent problem. In fact, some 30% of hypertensive patients are unable to reach their blood pressure goals. Thus, a new anti-hypertensive treatment, which acts on a broader patient population, would be an important addition to existing treatments. A number of vasoconstrictive agents, including angiotensin II, endothelin-1, and urotensin-II, exert their effect through RhoA and the downstream kinase Rho-kinase (ROCK1).1 Because of its central role in the control of smooth muscle contraction, inhibition of ROCK1 could lead to a more broadly efficacious anti-hypertensive agent.2 ROCK1 inhibitors have been shown to relax vascular smooth muscle and lower blood pressure in several animal models of hypertension.3 Therefore, we began an effort to identify potent ROCK1 inhibitors with pharmacokinetic profiles consistent with once daily oral dosing.
- Stavenger, Robert A.,Cui, Haifeng,Dowdell, Sarah E.,Franz, Robert G.,Gaitanopoulos, Dimitri E.,Goodman, Krista B.,Hilfiker, Mark A.,Ivy, Robert L.,Leber, Jack D.,Marino Jr., Joseph P.,Oh, Hye-Ja,Viet, Andrew Q.,Xu, Weiwei,Ye, Guosen,Zhang, Daohua,Zhao, Yongdong,Jolivette, Larry J.,Head, Martha S.,Semus, Simon F.,Elkins, Patricia A.,Kirkpatrick, Robert B.,Dul, Edward,Khandekar, Sanjay S.,Yi, Tracey,Jung, David K.,Wright, Lois L.,Smith, Gary K.,Behm, David J.,Doe, Christopher P.,Bentley, Ross,Chen, Zunxuan X.,Hu, Erding,Lee, Dennis
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- A COMPOSITION FOR TREATING OR PREVENTING A CANCER COMPRISING PYRROLOPYRIDINE DERIVATIVES
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The present invention provides a composition for treating or preventing a cancer comprising a pyrrolopyridine derivative or its salt and a pharmaceutically acceptable carrier.
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Page/Page column 11
(2010/11/25)
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- PYRIDONE SULFONAMIDES AND PYRIDONE SULFAMIDES AS MEK INHIBITORS
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This invention concerns N-(ortho phenylamino dihydropyridyl)sulfonamides and N-(ortho phenylamino dihydropyridyl), N′-alkyl sulfamides which are inhibitors of MEK and are useful in the treatment of cancer and other hyperproliferative diseases.
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Page/Page column 54
(2008/06/13)
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- PYRROLO[3,2-B]PYRIDINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
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The present invention provides novel pyrrolo[3,2-b]pyridine derivatives or pharmaceutically acceptable salts thereof, processes for the preparation thereof, and compositions comprising the same. The pyrrolo[3,2-b]pyridine derivatives or pharmaceutically acceptable salts thereof of the present invention have excellent proton pump inhibition effects and possess the ability to attain a reversible proton pump inhibitory effect.
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Page/Page column 7
(2010/10/20)
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- Foldamer-based pyridine-fullerene tweezer receptors for enhanced binding of zinc porphyrin
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This paper reports the design and synthesis of a new series of hydrogen bonding-mediated foldamer-derived tweezer receptors that are used for efficient complexation of zinc porphyrin guest. One end of the rigidified aromatic amide backbone is incorporated with one fullerene unit, while another end is connected to one pyridine or imidazole unit. The 1H NMR, UV-vis, and fluorescent investigations in chloroform revealed that, due to the intramolecular hydrogen bonding-driven preorganized folded conformation, the fullerene and pyridine units of the receptors are located with suitable spatial separation and consequently able to co-complex zinc porphyrin with remarkably increased stability. In contrast, the imidazole-incorporated receptor displays a weakened binding affinity possibly due to structural mismatching and large steric hindrance. The association constants of the complexes of the new receptors with zinc porphyrin have been determined.
- Wu, Zong-Quan,Li, Chang-Zhi,Feng, Dai-Jun,Jiang, Xi-Kui,Li, Zhan-Ting
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p. 11054 - 11062
(2007/10/03)
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- Lonidamine analogues and their use in male contraception and cancer treatment
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Novel compounds useful for inhibiting spermatogenesis and cancer treatment, and in particular as inhibitors of heat shock proteins and/or elongation factor 1 alpha.
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Page/Page column 24
(2008/06/13)
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- AKT PROTEIN KINASE INHIBITORS
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The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.
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Page/Page column 70
(2008/06/13)
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- PREPERATION OF 1,6-DISUBSTITUTED AZABENZIMIDAZOLES AS KINASE INHIBITORS
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Novel inhibitors of Rho-kinases are disclosed.
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Page/Page column 80; 83
(2008/06/13)
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- PREPARATION OF 1,7-DISUBSTITUTED AZABENZIMIDAZOLES AS KINASE INHIBITORS
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Novel inhibitors of Rho-kinases are disclosed.
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Page/Page column 20
(2008/06/13)
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- GABANERGIC MODULATORS
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This invention relates to the use of compounds of benzoindazole derivatives salts and solvates thereof for the preparation of a medicament for modulating alpha2 subtype GABA A receptors. The invention further relates to novel heterocyclic compounds and pharmaceutical compositions containing said compounds. In addition the invention relates to the use of compounds of formula (I) salts and solvates thereof for the preparation of a medicament for the treatment of depression, an anxiety disorder, a psychiatric disorder, a learning or cognitive disorder, a sleep disorder, a convulsive or seizure disorder or pain.
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Page/Page column 106
(2010/02/10)
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- Substituted indoles as inhibitors of poly (ADP-ribose) polymerase (PARP)
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The present invention relates to a series of substituted indole derivatives of the formula I: wherein R, R1, R2, R3, R4, X and Y are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5′-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.
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Page/Page column 24
(2010/02/11)
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- Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides
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This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with new piperidine 4-alkenyl derivatives that possess unique antiviral activity. More particularly, the present invention relates to compounds useful for the treatment of HIV and AIDS. The compounds of the invention for the general Formula I: wherein: Z is Q is selected from the group consisting of: —W— is
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Page/Page column 46
(2010/02/06)
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- Heterocyclic-ring condensed benzothiazine compound
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The invention provides a novel heterocyclic ring condensed benzothiazine compound which is effective for prevention or remedy of disease, in which histamine, leukotriene and the like participate. The heterocyclic ring condensed benzothiazine compound of the present invention or a pharmacologically acceptable salt thereof is effective for prevention or remedy of disease, in which a chemical mediator, such as histamine, leukotriene and the like, participate, for example, asthma, allergic coryza, atopic dermatitis, hives, hay fever, gastrointestinal allergy, food allergy and the like. Further, the heterocyclic ring condensed benzothiazine compound of the present invention, its pharmacologically acceptable salt or hydrates thereof is represented by the following formula: In the formula, the ring Het represents an unsaturated heterocyclic ring; R1and R2are the same as or different from each other, and each represents halogen atom, a lower alkyl group that may be substituted with a halogen atom, a lower alkoxy group that may be substituted with a halogen atom, a lower alkyl lower alkoxy group, cyano group; D represents a lower alkylene group and the like that may have a substituent; Q represents, for example, the formula —NR20R2(in the formula, R20and R21are the same as or different from each other, and each represents hydrogen atom, a lower alkyl group that may be substituted with a halogen atom, an aryl group that may have a substituent, an arylalkyl group that may have a substituent, a heteroaryl group that may have a substituent or a heteroarylalkyl group that may have a substituent, or R20and R21may form a 3- to 8-membered ring along with the nitrogen atom to which they are bound); and x represents an integer of from 1 to 2.
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- IL-8 receptor antagonists
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The present invention relates to the use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
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- Synthesis and SAR of a new series of COX-2-selective inhibitors: Pyrazolo[1,5-α]pyrimidines
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The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-α]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vivo (carrageenan-induced paw edema and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl) pyrazolo[1,5-α]pyrimidine (10f) as one of the most potent and selective COX-2 inhibitor in this series.
- Almansa,De Arriba,Cavalcanti,Gómez,Miralles,Merlos,García-Rafanell,Forn
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p. 350 - 361
(2007/10/03)
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- Cross coupling strategies towards the synthesis of the streptonigrin CD moiety
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An efficient route to an appropriate model of the streptonigrin 4- phenylpyridine CD moiety is reported. 4-Chloro-3-nitropyridine was found to be the key precursor and its reactivity in cross coupling reactions was further investigated.
- Crous, Renier,Dwyer, Catherine,Holzapfel, Cedric W.
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p. 721 - 726
(2007/10/03)
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- Dipeptides which promote release of growth hormone
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Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1
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- Synthesis of new dipyridotetraazapentalenes
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The new heteroaromatic compounds, dipyridotetraazapentalenes 3-5, were synthesized in two steps from readily available triazolopyridines 6 and 10. N-Arylation of 6 and 10 followed by subsequent reductive cyclization of the N-(nitropyridyl)-triazolopyridines with triethylphosphite in toluene afforded 3, 4 and 5, respectively, in good yield. Nitration of 3 afforded the new energetic tetranitrotetraazapentalene derivative 15 in 58% yield.
- Balachari, Devan,Trudell, Mark L.
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p. 8607 - 8610
(2007/10/03)
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- Design, synthesis, and structure-activity relationship studies of novel 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives as potent, orally active platelet-activating factor antagonists
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Replacement of the polar head of our previous series of 1-acyl-4-[(2-methyl-3-pyridyl)-cyanomethyl]piperazines with a 2-methylimidazo[4,5-c]pyridine group has led to the identification of a new series of 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives as potent, orally active platelet-activating factor (PAF) antagonists. On the basis of the general structure - activity relationship trends found for the acyl substituent in our earlier series, five groups of compounds were tested, diaryl- or alkylarylpropanoyl derivatives, their 3-hydroxy-substituted analogues, and urea, carbamate and amino acid derivatives. The optimal compound 19 (UR-12670), bearing the 3,3-diphenylpropanoyl moiety, exhibited very high in vitro and in vivo potency (IC50 = 0.0076 μM for the in vitro PAF-induced platelet aggregation assay, ID50 = 0.0086 mg/kg for the in vivo PAF-induced hypotension test in normotensive rats, and ID50 = 0.092 mg/kg po and 0.0008 mg/kg iv for the PAF-induced mortality test in mice). Compound 19 also showed long duration of activity. It gave 100% protection against PAF-induced mortality in mice 7 h after iv administration of a single dose of 1 mg/kg and also provided 100% inhibition of PAF-induced aggregation in dog whole blood 6 h after iv administration of the same dose. The lead structure 19 has been selected for in-depth pharmacological evaluation.
- Carceller, Elena,Merlos, Manuel,Giral, Marta,Balsa, Dolors,García-Rafanell, Julián,Forn, Javier
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p. 487 - 493
(2007/10/03)
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- Polyhydronorharman synthase inhibitors
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Selected acid functional polyhydronorharman type derivatives effective as thromboxane synthase inhibitors having the formula: STR1 where R1 and R2 are monovalent radicals, --(La)-- is a linking group of 4 to 8 chain atoms, and A is an acidic group.
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- Aminopyridine compounds
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An aminopyridine compound represented by the formula: STR1 wherein n represents 0 or 1; Z represents =S, =NCN or =CHNO2 ; R1 represents --NR3 R4, --NHNR3 R4, --NHCONHR3 or --NHSO2 R3 ; R2 represents H, or substituted or unsubstituted alkyl; R3 and R4, which may be the same or different, represent H, substituted or unsubstituted alkyl, aryl, substituted or unsubstituted acyl or alkoxycarbonyl group; and R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which R3 and R4 are bound, through another heteroatom or without it; an optical isomer thereof or art acid salt thereof, which is excellent in pharmacological effect and repressed in side effects as a drug for circulatory diseases.
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- Aminopyridine compounds
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An aminopyridine compound represented by the formula: STR1 wherein n represents 0 or 1; Z represents =S, =O, =NCN or =CHNO2 ; R1 represents --CN, --NR3 R4, --CONR3 R4, --NHNR3 R4, --NHCONHR3, --NHSO2 R3 or --SR3 ; R2 represents H, or substituted or unsubstituted alkyl; R3 and R4, which may be the same or different, represent H, substituted or unsubstituted alkyl, aryl, substituted or unsubstituted acyl or alkoxycarbonyl group; and R3 and R4 may form a heterocyclic ring together with a nitrogen atom to which R3 and R4 are bound, through another heteroatom or without it; or an acid salt thereof, which is excellent in pharmacological effect and repressed in side effects as a drug for circulatory diseases.
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- Pyrido[3,4-e]-1,2,4-triazines and related heterocycles as potential antifungal agents
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The preparation and biological activities of a series of pyrido[3,4-e]-1,2,4-triazines, 1,2,4-triazino[5,6-c]quinolines, and related fused triazines are described. Methyl, amino, and acylamino substituents were placed in the pyridyl ring of the former system. Other structural modifications included various alkyl, cycloalkyl, substituted phenyl, and heterocyclic groups in the 3-position of these ring systems. In agar dilution assays, actives in this series inhibited strains of Candida, Aspergillus, Mucor, and Trychophyton species at MIC's of ≤ 16 μg/mL.
- Reich,Fabio,Lee,Kuck,Testa
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p. 2474 - 2485
(2007/10/02)
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- Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 8. Molecular dissections of carbocyclic 3-deazaadenosine as inhibitors of S-adenosylhomocysteine hydrolase
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A series of 9-(hydroxyalkyl)-3-deazaadenines, which are analogues of the carbocyclic derivative of 3-deazaadenosine (3-deaza-C-Adpo), were synthesized. The analogues were tested as inhibitors of bovine liver S-adenosyl-L-homocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus (WR) replication in clone 929 mouse L cells and the results were compared to those observed for the parent compound, 3-deaza-C-Ado. 4-Amino-1-(2,3-dihydroxy-1-propyl)imidazo[4,5-c]pyridine (14), the analogue which included the 1'-, 2'- and 3'-carbons of 3-deaza-C-Ado, was the most active inhibitor toward purified AdoHcy hydrolase. The inhibitory effect of 14 (K(i) = 768 nM) on AdoHcy hydrolase was significantly less than that observed for 3-deaza-C-Ado (K(i) = 4 nM). Analogue 14 also exhibited inhibitory activity against vaccinia virus replication, but the activity was less than that observed with 3-deaza-C-Ado. 4-Amino-1-(4-hydroxy-1-butyl)imidazo[4,5-c]pyridine (15) showed little or no inhibitory activity toward AdoHcY hydrolase, but it did exhibit antiviral effects comparable to 14. These results suggest that 3-deaza-C-Ado and analogue 14 may be producing their antiviral effects by altering a critical viral methylation (e.g., methylation of the 5'-cap of viral mRNA), whereas analogue 15 may be acting through an alternative mechanism.
- Houston,Dolence,Keller,Patel-Thombre,Borchardt
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p. 467 - 471
(2007/10/02)
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- Nitro, amino and aroylamino-N-phenylpyridinamines in a process for preparing pyrido[1,4]benzodiazepines
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Nitro, amino and aroylamino-N-phenylpyridinamines as chemical intermediates and/or having antidepressant activity having the formula STR1 wherein R3 is nitro, amino or aroylamino, and Q is hydrogen, --NR1 R2 or halogen are disclosed in a process for preparing pyrido[1,4]benzodiazepines.
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- [2-[(Nitropyridinyl)amino]phenyl]arymethanones
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[2-[(Nitropyridinyl)amino]phenyl]arylmethanones as chemical intermediates and/or having antidepressant activity having the formula: STR1 wherein: B is carbonyl, thioxomethyl, ketal or thioketal, R is hydrogen or -alk1 -Q, Q is hydrogen, --NR1 R2 or halogen are disclosed in a process for preparing pyrido[1,4]benzodiazepines.
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