- FREE RADICAL CHLORINATION OF METHYL DERIVATIVES OF PYRIDINE, PYRAZINE, AND THIAZOLE BY N-CHLOROSUCCINIMDE
-
When methylazines (2-, 3-, and 4-methylpyridines, methylpyrazine) are treated with N-chlorosuccinimide they undergo successive chlorination of the methyl group to give 2-chloromethylpyridine, 2-dichloromethylpyridine, and dichloromethylpyrazine in preparative yields. 3-Dichloromethylpyridine was synthesized from pyridine-3-aldehyde and PCl5.The primary chlorination products of 4-methylthiazole are 4-methyl-5-chlorothiazole and 5-chloro-4-chloromethylthiazole.
- Rubina, K. I.,Iovel', I. G.,Gol'dberg, Yu. Sh.,Shimanskaya, F. V.
-
-
Read Online
- New strategy for quantifying biological zinc by a modified zinpyr fluorescence sensor
-
Substitution of one pyridine by pyrazine in each DPA appendage of ZP1 leads to a new zinc sensor, ZPP1, with a modified background fluorescence and zinc affinity. ZPP1 exhibits a two-step zinc response during fluorescence titrations, which leads to a new method for zinc quantification. The ability of ZPP1 to image and quantify zinc was demonstrated in pancreatic Min6 cells. Copyright
- Zhang, Xiao-An,Hayes, Dugan,Smith, Sarah J.,Friedle, Simorie,Lippard, Stephen J.
-
-
Read Online
- Synthesis and characterization of nitrogen-rich macrocyclic ligands and an investigation of their coordination chemistry with lanthanum(III)
-
Derivatives of the ligand 1,4,7,10-tetraazacyclododecane (cyclen) containing pendant N-heterocyclic donors were prepared. The heterocycles pyridine, pyridazine, pyrimidine, and pyrazine were conjugated to cyclen to give 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (Lpy), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (Lpyd), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (Lpyr), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (Lpz), respectively. The coordination chemistry of these ligands was explored using the La3+ ion. Accordingly, complexes of the general formula [La(L)(OTf)](OTf)2, where OTf = trifluoromethanesulfonate and L = Lpy (1), Lpyd (2), Lpyr (3), and Lpz (4), were synthesized and characterized by NMR spectroscopy. Crystal structures of 1 and 2 were also determined by X-ray diffraction studies, which revealed 9-coordinate capped, twisted square-antiprismatic coordination geometries for the central La3+ ion. The conformational dynamics of 1-4 in solution were investigated by variable-temperature NMR spectroscopy. Dynamic line-shape and Eyring analyses enabled the determination of the activation parameters for the interconversion of enantiomeric forms of the complexes. Unexpectedly, the different pendant N-heterocycles of 1-4 give rise to varying values for the enthalpies and entropies of activation for this process. Density functional theory calculations were carried out to investigate the mechanism of this enantiomeric interconversion. Computed activation parameters were consistent with those experimentally determined for 1 but differed somewhat from those of 2-4.
- Wilson, Justin J.,Birnbaum, Eva R.,Batista, Enrique R.,Martin, Richard L.,John, Kevin D.
-
-
Read Online
- Mononuclear Fe(II) Complexes Based on the Methylpyrazinyl-Diamine Ligand: Chemical-, Thermo- and Photocontrol of Their Magnetic Switchability
-
Two new mononuclear Fe(II) complexes, [Fe(2MeLpz)(NCX)2] (L = N,N′-dimethyl-N,N′-bis((pyrazin-2-yl)methyl)-1,2-ethanediamine and X = S (1), BH3 (2)), have been synthesized and characterized by single-crystal X-ray diffraction, magnetic, optical reflectivity, and photomagnetic measurements. They have similar FeN6 coordination environments offered by the tetradentate ligand with a cis-α conformation and two NCX- coligands in cis positions. However, 1 and 2 have different molecular arrangements and crystal packings, and are isolated in orthorhombic Pbnb and monoclinic C2/c space groups, respectively. 1 remains in a high spin state (S = 2) over all temperatures while 2 undergoes a spin transition around 168 K with a small thermal hysteresis of about 0.4 K (at a temperature scan rate of 1.3 K min-1). This phase transition, which can also be optically detected due to the associated marked change of the sample color, occurs between two structurally characterized phases, which exhibit Fe(II) complexes in their high spin and low spin states at high and low temperatures, respectively. The reversible photoswitching between these two states has also been confirmed at low temperatures using well separated wavelength irradiations.
- Liu, Xue,Zhou, Jian,Bao, Xin,Yan, Zheng,Peng, Guo,Rouzières, Mathieu,Mathonière, Corine,Liu, Jun-Liang,Clérac, Rodolphe
-
-
Read Online
- Hederagenin compound H-X with anti-lung cancer effect and preparation method and application thereof
-
The invention provides a hederagenin compound H-X with an anti-tumor effect and a preparation method and application thereof. The structural general formula 1 is shown in the specifications. Most of the derivatives provided by the invention have obvious inhibition effects on tumor cells A549, MCF-7 and HepG2, and the compound hederagenin-2, 6-dimethylpyrazine (H-08) shows good selectivity betweentumors and normal conditions, especially on lung cancer A549 cells. The IC50 of the compound to A549, MCF-7, HepG2, MDCK and H9c2 is 3.45+/-0.59 muM, 8.73+/-1.49 muM, 8.71+/-0.38 muM, 14.11+/-0.04 muM, and 16.69+/-0.12 muM, the inhibition effect on A549 cells is similar to that of a positive drug cis-platinum (IC50 is 3.85+/-0.63 muM), but the toxicity on MDCK and H9c2 is obviously lower than thatof cis-platinum.
- -
-
Paragraph 0045; 0046; 0118; 0119
(2020/04/17)
-
- Monoacylglycerol Lipase Modulators
-
Fused compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. Wherein R1, R2, R2a, R3, R3a, R4, and R4a are defined herein.
- -
-
Paragraph 0371; 0528
(2020/04/24)
-
- NOVEL TETRAZOLE COMPOUNDS AND THEIR USE IN THE TREATMENT OF TUBERCULOSIS
-
The invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis.
- -
-
Page/Page column 91
(2019/03/05)
-
- Design, synthesis, and cytotoxic analysis of novel hederagenin–pyrazine derivatives based on partial least squares discriminant analysis
-
Hederagenin (He) is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new He–pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents; they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of these derivatives showed much stronger cytotoxic activity than He. Remarkably, the most potent was compound 9 (half maximal inhibitory concentration (IC50) was 3.45 ± 0.59 μM), which exhibited similar antitumor activities against A549 (human non-small-cell lung cancer) as the positive drug cisplatin (DDP; IC50 was 3.85 ± 0.63 μM), while it showed lower cytotoxicity on H9c2 (murine heart myoblast; IC50 was 16.69 ± 0.12 μM) cell lines. Compound 9 could induce the early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549 cells. Impressively, we innovatively introduced the method of cluster analysis modeled as partial least squares discriminant analysis (PLS-DA) into the structure–activity relationship (SAR) evaluation, and SAR confirmed that pyrazine had a profound effect on the antitumor activity of He. The present studies highlight the importance of pyrazine derivatives of He in the discovery and development of novel antitumor agents.
- Fang, Kang,Zhang, Xiao-Hua,Han, Yao-Tian,Wu, Gao-Rong,Cai, De-Sheng,Xue, Nan-Nan,Guo, Wen-Bo,Yang, Yu-Qin,Chen, Meng,Zhang, Xin-Yu,Wang, Hui,Ma, Tao,Wang, Peng-Long,Lei, Hai-Min
-
-
- SUBSTITUTED 1H-IMIDAZO[4,5-B]PYRIDIN-2(3H)-ONES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS
-
Substituted 1 H-imidazo[4,5-b]pyridin-2(3H)-ones as NR2B receptor ligands. Such compounds may be used in NR2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by NR2B receptor activity.
- -
-
Page/Page column 103
(2018/04/23)
-
- Preparation method of medical intermediate N-(2-methylpyrazine)benzylamine phosphate compound
-
The invention discloses a preparation method of a medical intermediate N-(2-methylpyrazine)benzylamine phosphate compound. The method includes the steps of: under the protection of nitrogen, adding 2-methylpyrazine, dibenzoyl peroxide and N-chlorosuccinimide in a mole ratio of 1:0.05-0.1:1-1.4 into a solvent anhydrous carbon tetrachloride, and carrying out reflux reaction to obtain alpha-chloromethyl pyrazine; adding benzylamine and cesium hydroxide in a mole ratio of 1:1-1.3 into a solvent anhydrous dimethylformamide, under stirring, adding alpha-chloromethyl pyrazine according to a alpha-chloromethyl pyrazine/benzylamine mole ratio of 1:1-1.3, thus obtaining N-(2-methylpyrazine)benzylamine phosphate with a content of 95-97%; and subjecting the N-(2-methylpyrazine)benzylamine phosphate to recrystallization in methanol-chloroform, thus obtaining a N-(2-methylpyrazine)benzylamine phosphate product with a content of more than 99.5%. The method has the advantages of easily available raw materials, high total yield, and simple post-treatment.
- -
-
Paragraph 0034; 0041; 0046; 0051; 0056
(2017/08/27)
-
- NOVEL CLOSTRIDIUM DIFFICILE TOXIN INHIBITORS
-
The present invention relates to benzodiazepine derivative compounds of formula (I), or pharmaceutically acceptable salts thereof. The present benzodiazepine compounds are useful Clostridium difficile inhibitors in the treatment of Clostridium difficile infection in humans. The present invention provides a pharmaceutical composition containing benzodiazepine compounds of formula (I) and a method of making as well as a method of using the same in treating patients infected with Clostridium difficile infection by administering the same. The compounds of the present invention may be used in combination with additional antibiotics or anti-toxin antibody drugs.
- -
-
-
- Hetero-aromatic compound and its use in medicine (by machine translation)
-
The invention discloses heteroaromatic compound and its use in medicine, in particular, the invention provides a hetero-aromatic compound or its stereoisomers, geometric isomers, tautomers, racemate, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug, and containing said pharmaceutical composition; the invention also discloses the compound or its pharmaceutical compositions in use for preparing a medicament, and in the treatment of autoimmune diseases or proliferative diseases of application. (by machine translation)
- -
-
Paragraph 0782; 0783
(2017/08/29)
-
- Improved Halogenation of Methyl Aromatics and Methyl Heteroaromatics: Unexpected Reactivity of Tetrahalogeno-diphenylglycolurils
-
1,3,4,6-Tetrachloro (TCDGU) and 1,3,4,6-tetrabromo-3α,6α-diphenylglycolurils smooth halogen oxidizers have been exploited in a new direction as reagents for free radical substitution toward some N-halosuccinimide nonreactive bis-heterocycles. An unexpected selectivity and reactivity were observed with methyl benzenes, methyl heterocycles, and methyl-bis-heterocycles of interest. A chemometric study has been performed to optimize five independent factors of the chlorination reaction with TCDGU. The predictive model was established either for the halogenation conversion and the ratio of monochlorination.
- Moretti, Florian,Poisson, Guillaume,Marsura, Alain
-
p. 173 - 183
(2016/05/19)
-
- PYRIDO[2,3-d]PYRIMIDIN-4-ONE COMPOUNDS AS TANKYRASE INHIBITORS
-
Pyrido[2,3-d]pyrimidin-4-one compounds, formulations containing those compounds, and their use as tankyrase 1 and 2 inhibitors Formula (I).
- -
-
Page/Page column 17
(2015/05/26)
-
- FUSED PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON FMS KINASES
-
Disclosed are a fused pyrimidine derivative of formula (I), and a pharmaceutically acceptable salt, stereoisomer, hydrate and solvate thereof, which have an excellent inhibitory activity on FMS kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating diseases caused by abnormal activation of FMS kinases such as immunologic diseases, metabolic diseases, inflammatory diseases, cancers and tumors.
- -
-
Page/Page column 46; 47
(2014/01/17)
-
- IMIDAZOTRIAZINONE COMPOUNDS
-
The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.
- -
-
-
- OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
-
The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.
- -
-
Page/Page column 83
(2012/05/05)
-
- IMIDAZOTRIAZINONE COMPOUNDS
-
The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including CNS or neurodegeneration disorder.
- -
-
-
- Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
-
1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
- Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
-
experimental part
p. 4721 - 4734
(2011/09/19)
-
- HYDRAZONE COMPOUNDS AND THEIR USE
-
The present invention relates to hydrazone compounds of Formula I: (I) and pharmaceutically acceptable salts and stereoisomers thereof, wherein R1, R2, R3, R4, L1, and L2 are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I as inhibitors of TRPM5 protein.
- -
-
Page/Page column 116
(2010/12/17)
-
- Intermolecular S...π interactions in crystalline sulfanyl-triazine derivatives
-
Three types of intermolecular S...π interaction geometry are identified in the crystal structures of four sulfanyl-triazine derivatives bearing pendant heterocyclic rings, in which the triazinyl, pyrazinyl, pyrimidinyl and pyridyl rings are found to exhibit different affinities for the divalent S atom.
- Wan, Chong-Qing,Han, Jie,Mak, Thomas C. W.
-
experimental part
p. 707 - 712
(2009/06/20)
-
- 3-SUBSTITUTED-[1,2,3]BENZOTRIAZINONE COMPOUNDS FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES
-
This invention relates to the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for higher order behaviors. These brain networks are involved in cognitive abilities related to memory impairment, such as is observed in a variety of dementias and in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia and affective disorders. In a particular aspect, the present invention relates to compounds useful for treatment of such conditions, and methods of using these compounds for such treatment.
- -
-
Page/Page column 88
(2008/12/07)
-
- Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds
-
The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38α MAP kinase with good cellular potency toward the inhibition of TNF-α production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38α is also disclosed.
- Murali Dhar,Wrobleski, Stephen T.,Lin, Shuqun,Furch, Joseph A.,Nirschl, David S.,Fan, Yi,Todderud, Gordon,Pitt, Sidney,Doweyko, Arthur M.,Sack, John S.,Mathur, Arvind,McKinnon, Murray,Barrish, Joel C.,Dodd, John H.,Schieven, Gary L.,Leftheris, Katerina
-
p. 5019 - 5024
(2008/03/11)
-
- Pyridazinoquinolinetriones as NMDA glycine-site antagonists with oral antinociceptive activity in a model of neuropathic pain
-
A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyi)alkyl]-pyridazino[4,5-b] quinoline-1,4,10(5H)-triones were synthesized and found to have potent activity at the glycine site of the NMDA receptor. In some cases, these compounds possessed poor aqueous solubility that may have contributed to poor rat oral bioavailability. Subsequently, compounds have been identified with improved aqueous solubility and oral bioavailability. Several of these compounds were examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and found to have potent activity when dosed orally.
- Bare, Thomas M.,Brown, Dean G.,Horchler, Carey L.,Murphy, Megan,Urbanek, Rebecca A.,Alford, Vernon,Barlaam, Christine,Dyroff, Martin C.,Empfield, James B.,Forst, Janet M.,Herzog, Keith J.,Keith, Richard A.,Kirschner, Alan S.,Lee, Chi-Ming C.,Lewis, Joseph,McLaren, Frances M.,Neilson, Kathy L.,Steelman, Gary B.,Trivedi, Shephali,Vacek, Edward P.,Xiao, Wenhua
-
p. 3113 - 3131
(2008/02/06)
-
- Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazines as GABAA receptor agonists at the α3 subunit
-
We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the 0.3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at α1 and antagonism at α3 (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.
- Russell, Michael G. N.,Carling, Robert W.,Atack, John R.,Bromidge, Frances A.,Cook, Susan M.,Hunt, Peter,Isted, Catherine,Lucas, Matt,McKernan, Ruth M.,Mitchinson, Andrew,Moore, Kevin W.,Narquizian, Robert,Macaulay, Alison J.,Thomas, David,Thompson, Sally-Anne,Wafford, Keith A.,Castro, José L.
-
p. 1367 - 1383
(2007/10/03)
-
- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
-
The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
- -
-
Page/Page column 82-83
(2008/06/13)
-
- NOVEL BENSOPHENONE DERIVATIVES OR SALTS THEREOF
-
A benzophenone derivative represented by the following formula: whereinR1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R2 represents, for example, a carboxyl group optionally protected with alkyl;R3 represents, for example, an optionally protected hydroxyl group; R4 represents, for example, an optionally substituted cycloalkyloxy group; and R5 represents, for example, a hydrogen atom, ???or a salt thereof has anti-arthritic activity, inhibits bone destruction caused by arthritis, and provides high safety and excellent pharmacokinetics and thus is useful as therapeutic agent for arthritis. These compounds have inhibitory effect on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression of AP-1 is involved.
- -
-
-
- 3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and Analogues: High-Affinity γ-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with α2, α3, and α5-Subtype Binding Selectivity over α1
-
Studies with our screening lead 5 and the literature compound 6 led to the identification of 6-benzyloxy-3-(4-methoxy)phenyl-1,2,4-triazolo[3,4-a]phthalazine 8 as a ligand with binding selectivity for the γ-aminobutyric acid-A (GABA-A) α3- and α5-containing receptor subtypes over the GABA-A α1 subtype (Ki: α2 = 850 nM, α3 = 170 nM, α5 = 72 nM, α1 = 1400 nM). Early optimization studies identified the close analogue 10 (Ki: α2 = 16 nM, α3 = 41 nM, α5 = 38 nM, α1 = 280 nM) as a suitable lead for further study. High-affinity ligands were identified by replacing the 6-benzyloxy group of compound 10 with 2-pyridylmethoxy (compound 29), but binding selectivity was not enhanced (K i: α2 = 1.7 nM, α3 = 0.71 nM, α5 = 0.33 nM, α1 = 2.7 nM). Furthermore, on evaluation in xenopus oocytes, 29 was discovered to be a weak to moderate inverse agonist at all four receptor subtypes α1, -7%; α2, -5%; α3, -16%; α5, -5%). Replacement of the 3-phenyl group of 29 with alternatives led to reduced affinity, and smaller 3-substituents led to reduced efficacy. Methyl substitution of the benzo-fused ring of 29 at the 7-, 8-, and 10-positions resulted in increased efficacy although selectivity was abolished. Increased efficacy and retention of selectivity for α3 over α1 was achieved with the 7,8,9,10-tetrahydro-(7,10-ethano)-phthalazine 62. Compound 62 is currently one of the most binding selective GABA-A α3-benzodiazepine-site partial agonists known, and although its selectivity is limited, its good pharmacokinetic profile in the rat (33% oral bioavailability after a 3 mg/kg dose, reaching a peak plasma concentration of 179 ng/mL; half-life of 1 h) made it a useful pharmacological tool to explore the effect of a GABA-A α2/α3 agonist in vivo.
- Carling, Robert W.,Moore, Kevin W.,Street, Leslie J.,Wild, Deborah,Isted, Catherine,Leeson, Paul D.,Thomas, Steven,O'Connor, Desmond,McKernan, Ruth M.,Quirk, Katherine,Cook, Susan M.,Atack, John R.,Wafford, Keith A.,Thompson, Sally A.,Dawson, Gerard R.,Ferris, Pushpinder,Castro, José L.
-
p. 1807 - 1822
(2007/10/03)
-
- Substituted triazolo-pyridazine derivatives as ligands for GABA receptors
-
Substituted triazolo-pyridazine derivative compounds represented by wherein the variables are disclosed herein are selective ligands for GABA-A receptors, particularly for the α2 and/or α3 subunits.
- -
-
-
- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
-
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
- -
-
-
- (Azaarylmethoxy)indoles as inhibitors of leukotriene biosynthesis
-
Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.
- -
-
-
- PIPERIDINE TACHYKININ RECEPTOR ANTAGONISTS
-
Compounds of formula (I), and salts and prodrugs thereof STR1 wherein n is 1, 2 or 3;X represents O or S;Y represents a hydrocarbon chain of 1, 2, 3 or 4 carbon atoms optionally substituted by oxo;R 1 is phenyl optionally substituted by 1, 2 or 3 of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl,--OR a, SR a, SOR a, SO 2 R a,--NR a R b,--NR a COR b,--NR a CO 2 R b,--CO 2 R a or--CONR a R b ;R 2 is phenyl, indazolyl, thienyl, furyl, pyridyl, thiazolyl, tetrazolyl, quinolyl, benzhydryl, or benzyl;R 4 and R 5 each independently represent H, halo, C 1-6 alkyl, oxo, CH 2 OR a, CO 2 R a or CONR. sup.a R b ;R 8 represents an optionally substituted aromatic heterocycle; andR a and R b are H, trifluoromethyl, C 1-6 alkyl or phenyl optionally substituted by C. sub.1-6 alkyl, halo or trifluoromethyl; are tachykinin antagonists useful in medicine.
- -
-
-
- N-heterocyclic compounds as radioprotectors. 1. 2-Pyridinemethanethiol, 2-pyrazinemethanethiol and related compounds
-
2-Pyridinemethanethiol 1, which is structurally related to cysteamine, showed good radioprotective potency in mice, but 2-pyrazinemethanethiol 9 was inactive. Certain derivatives of 1 and 9 that were synthesized were radioprotective. The 3 isomeric mercaptopyridines showed activity. Further study of N-heteroaromatic compounds as radioprotectors is indicated. An improved method for the preparation of 9 is described.
- Barnes,Fatome,Esslemont,Jones
-
p. 515 - 519
(2007/10/02)
-
- 2-Alkoxy(and 2-amino)-3-amino-2-heterocyclic-thiopropanamides
-
The compounds are 2-alkoxy(and 2-amino)-3-amino-2-heterocyclic-thiopropanamides, for example 2-methoxy-N-methyl-3-morpholino-2-(2-pyridyl)thiopropanamide, which are inhibitors of gastric acid secretion.
- -
-
-