- Toxicity of the amphetamine metabolites 4-hydroxyamphetamine and 4-hydroxynorephedrine in human dopaminergic differentiated SH-SY5Y cells
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Amphetamine (AMPH) is a psychostimulant used worldwide by millions of patients in the clinical treatment of attention deficit hyperactivity disorder, narcolepsy or even obesity, and is also a drug of abuse. 4-Hydroxynorephedrine (4-OHNE) and 4-hydroxyamphetamine (4-OHAMPH) are two major metabolites known to persist in the brain longer than AMPH. The contribution of AMPH metabolites for its neurotoxicity is undetermined. We evaluated the toxicity of AMPH and its metabolites 4-OHNE and 4-OHAMPH, obtained by chemical synthesis, in human dopaminergic differentiated SH-SY5Y neurons. Cells were exposed to AMPH (concentration range 0–5 mM) or 4-OHAMPH or 4-OHNE (concentration range 0–10 mM) for 24 or 48 h, and the viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) leakage assays. Results showed that for both AMPH and the metabolites a concentration-dependent toxicity was observed. The toxic concentration 50% (TC50) for AMPH and 4-OHNE following 24 h exposure was circa 3.5 mM and 8 mM, respectively. For 4-OHAMPH the TC50 was not reached in the tested concentration range. N-acetyl cysteine, cycloheximide, L-carnitine, and methylphenidate were able to reduce cell death induced by AMPH TC50. Acridine orange/ethidium bromide staining showed evident signs of late apoptotic cells and necrotic cells following 24 h exposure to AMPH 3.50 mM. The 4-OHAMPH metabolite at 8.00 mM originated few late apoptotic cells, whereas 4-OHNE at 8.00 mM resulted in late apoptotic cells and necrotic cells, in a scenario similar to AMPH. In conclusion, the AMPH metabolite 4-OHNE is more toxic than 4-OHAMPH, nonetheless both are less toxic than the parent compound in vitro. The most toxic metabolite 4-OHNE has longer permanence in the brain, rendering likely its contribution for AMPH neurotoxicity.
- Feio-Azevedo,Costa,Ferreira,Branco,Pereira,Bastos,Carvalho,Capela
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Read Online
- Synthesis, Antiproliferative Effect, and Topoisomerase II Inhibitory Activity of 3-Methyl-2-phenyl-1 H-indoles
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A series of 3-methyl-2-phenyl-1H-indoles was prepared and investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI50 values of the most potent compounds (32 and 33) were lower than 5 μM in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted the good correlation between the antiproliferative effect and topoisomerase II inhibition. The most potent derivative, 32, was shown to induce the apoptosis pathway. The obtained results highlight 3-methyl-2-phenyl-1H-indole as a promising scaffold for further optimization of compounds with potent antiproliferative and antitopoisomerase II activities.
- Argaez, Aida Nelly Garcia,Dalla Via, Lisa,Hyeraci, Mariafrancesca,Kikelj, Danijel,Ma?i?, Lucija Peterlin,Passarella, Daniele,Secci, Daniela,Toma?i?, Tihomir,Zidar, Nace
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p. 691 - 697
(2020/07/14)
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- BETA-HYDROXYETHYLAMINES FOR USE IN THE TREATMENT OR PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASES
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There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of a non-alcoholic fatty liver disease (NAFLD), such as non-alcoholic steatohepatitis (NASH), wherein X, R1, R2, R3 and n have meanings as provided in the description.
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- Heteroaryl estrogen receptor regulating agent and application thereof
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The invention provides a compound as shown in a formula (I) and a heteroaryl estrogen receptor regulating agent including the same, belonging to the technical field of medicines. The heteroaryl estrogen receptor regulating agent further comprises a calcium phosphosilicate microsphere carrier, wherein the carrier includes silicon oxide, calcium oxide and phosphorus pentoxide in a weight ratio of 20: 4: 1, and the diameters of the microspheres are in a range of 300 to 1100 nm. The compound and the regulating agent provided by the invention can be used as estrogen receptor degrading agents, AKR1C3 inhibitors and bone resorption inhibitors for treating estrogen receptor related diseases or illnesses of patients and can be applied to the treatment of breast cancer, endometriosis and osteoporosis. The preparation method for the regulating agent can prolong the shelf life of the compound, increase the loading amount of a microsphere product, and enhance the stability and sustained release performance of the regulating agent; and the regulating agent provides a supersaturation amount of Ca in a biological fluid environment for binding to bone tissue nucleation sites so as to promote regeneration or repairing of bone tissue.
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- PROCESS FOR THE PREPARATION OF BAZEDOXIFENE
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The invention relates to a process for preparation of the compound 3-methyl-5-benzyloxy-2-(4-benzyloxyphenyl)-1H-indole 5, an intermediate for the synthesis of bazedoxifene and bazedoxifene acetate.
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- INDOLE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
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The present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.
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- COMPOUNDS FOR THE TREATMENT OF HYPERGLYCAEMIA
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There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of hyperglycaemia or a disorder characterized by hyperglycaemia, such as type 2 diabetes, wherein X, R1, R2, R3 and n have meanings as provided in the description.
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- Piperazinone compounds and application thereof
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The invention belongs to the technical field of medicine and relates to 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione as well as a medical application, a stereoisomer and pharmaceutically acceptable salt thereof. The structural formula of 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl] butyl]piperazine-2,3-dione is represented in the specification; 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione and pharmaceutically acceptable acid addition salt of the compound can be combined with existing drugs or can be independently used as an estrogen receptor modulator for treating or preventing various estrogen function related diseases such as bone loss, fracture, osteoporosis, hectic fever, LDL cholesterol level rise, cardiovascular disease, cognitive impairment, brain degeneration disease and anxiety, as well as depression, sexual dysfunction, hypertension, retinal degeneration and cancer caused by estrogen deficiency, especially osteoporosis.
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- Aq HBr–NaNO2–KI/air: a new catalytic system for α-monobromination of ketones
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An efficient approach for α-bromination of aryl alkyl ketones, utilizing a system consisting of aqueous hydrobromic acid as bromine source, sodium nitrite–KI as catalyst, and air as terminal oxidant, has been developed. The method offers advantages of selective monobromination, mild reaction conditions, broad substrate scope, and good yield. The use of air as the terminal oxidant makes the reaction very attractive from both economical and environmental viewpoints.
- Ghorpade, Archana K.,Huddar, Sameerana N.,Akamanchi, Krishnacharya G.
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supporting information
p. 4918 - 4921
(2016/10/22)
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- Wavelength-dependent optoacoustic imaging probes for NMDA receptor visualisation
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The cellular localisation and binding specificity of two NMDAR-targeted near-IR imaging probes has been examined by microscopy, followed by exemplification of MSOT to monitor simulated glutamate bursts in cellulo and a preliminary study in mice observing the signal in the brain.
- Sim, Neil,Gottschalk, Sven,Pal, Robert,Delbianco, Martina,Degtyaruk, Oleksiy,Razansky, Daniel,Westmeyer, Gil G.,Ntziachristos, Vasilis,Parker, David,Mishra, Anurag
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supporting information
p. 15149 - 15152
(2015/10/12)
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- Bazedoxifene-scaffold-based mimetics of solomonsterols A and B as novel pregnane x receptor antagonists
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Pregnane X receptor (PXR), a member of the NR1I nuclear receptor family, acts as a xenobiotic sensor and a paramount transcriptional regulator of drug-metabolizing enzymes and transporters. The overexpression of PXR in various cancer cells indicates the importance of PXR as a drug target for countering multidrug resistance in anticancer treatments. We describe the discovery of novel bazedoxifene-scaffold-based PXR antagonists inspired by the marine sulfated steroids solomonsterol A and B as natural leads. A luciferase reporter assay on a PXR-transfected HepG2 cell line identified compounds 19-24 as promising PXR antagonists. Further structure-activity relationship studies of the most active PXR antagonist from the series (compound 20, IC50 = 11 μM) revealed the importance of hydroxyl groups as hydrogen-bond donors for PXR antagonistic activity. PXR antagonists 20 and 24 (IC50 = 14 μM), in addition to the downregulation of PXR expression, exhibited inhibition of PXR-induced CYP3A4 expression, which illustrates their potential to suppress PXR-regulated phase-I drug metabolism.
- Hodnik, ?iga,Peterlin Ma?i?, Lucija,Toma?i?, Tihomir,Smodi?, Domen,D'Amore, Claudio,Fiorucci, Stefano,Kikelj, Danijel
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p. 4819 - 4833
(2014/07/07)
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- Synthesis and evaluation of 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as COX-2 and serotonin reuptake inhibitors
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Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50 = 0.78 μM) than ibuprofen (IC 50 = 7.6 μM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity. A series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen were tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. Most of the compounds possess good COX-2 selectivity. Compound 1k shows better COX-2 inhibitory activity than ibuprofen and possesses favorable serotonin reuptake inhibitory activity. According to the results of the biological assays, 2-arylmorpholine-substituted ibuprofen could be used as a core structure to design novel dual COX-2 and serotonin reuptake inhibitors.
- Dou, Jie,Shi, Lei,Hu, Aixi,Dong, Minyu,Xu, Jiangping,Liu, Ailin,Jiang, Yiping
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- In vitro bioactivation of bazedoxifene and 2-(4-hydroxyphenyl)-3-methyl-1H- indol-5-ol in human liver microsomes
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Bazedoxifene is a selective estrogen receptor modulator (SERM) that has been developed for use in post-menopausal osteoporosis. However, it contains a potentially toxic 5-hydroxy-3-methylindole moiety. Previous studies on the 5-hydroxyindole and the 3-alkylindole-containing drugs indometacine, zafirlukast and MK-0524 structural analogs have shown that they are bioactivated by cytochrome P450s through a dehydrogenation process to form quinoneimine or 3-methyleneindolenine electrophilic species. In the present study, bazedoxifene was synthesized and then evaluated, together with raloxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol (13), a 3-methyl-5-hydroxyindole- based structural fragment of bazedoxifene, for its ability to form reactive electrophilic species when incubated with human liver microsomes (HLMs) or recombinant CYP isozymes. We showed that bazedoxifene was bioactivated only in trace amounts with recombinant CYP isozymes. In contrast, the N-dealkylated fragment of bazedoxifene (2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol) was bioactivated in considerable amounts to an electrophilic intermediate, which was trapped with glutathione and identified by LC-MS/MS. This suggests that bazedoxifene would require initial N-dealkylation, which could subsequently lead to the formation of the reactive intermediate. However, such an N-dealkylated metabolite of bazedoxifene was not detected after the incubation of bazedoxifene in HLM or recombinant CYP isozymes.
- Lu?in, Tina Trdan,Toma?i?, Tihomir,Trontelj, Jurij,Mrhar, Ale?,Peterlin-Ma?i?, Lucija
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- Design, synthesis and biological evaluation of 2-(2-aryl-morpholino-4-yl) ethyl esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors
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A number of novel 2-(2-arylmorpholino-4-yl)ethyl 1-(4-chlorobenzoyl)-5- methoxy-2-methyl-1H-indol-3-acetate hydrochlorides were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds exhibited moderate to good selective COX-2 inhibition, and subtle structural changes in the substituents on the side chain of the ester moiety altered the inhibitory properties significantly. 2-[2-(4-Butoxyphenyl) morpholino-4-yl]ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1f), showed good selective COX-2 inhibitory activity (Selective index (SI) 182), which is comparative with celecoxib (SI 214), a COX-2 inhibitor of diarylpyrazoles. While 2-[2-(2,4-dichloro-5-fluorophenyl)morpholino-4-yl] ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1g), showed greater selective COX-2 inhibitory activity (SI 358) than celecoxib. Both compounds were identified as compromising derivatives in this class to reduce the side effects generated by nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin.
- Shi, Lei,Hu, Aixi,Xu, Jiangping,Jiang, Yiping
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scheme or table
p. 1339 - 1344
(2012/08/29)
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- 5-Aryl-imidazolin-2-ones as a scaffold for potent antioxidant and memory-improving activity
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A series of 5-phenyl-substituted-N-alkyl-imidazolin-2-ones with potent radical-scavenging activity and lipid peroxidation inhibitory activity was synthesized. Many of the compounds showed memory-improving effect in animal models independent of the inhibitory activity on lipid peroxidation.
- Watanabe, Kazutoshi,Morinaka, Yasuhiro,Hayashi, Yoshio,Shinoda, Masaki,Nishi, Hiroyoshi,Fukushima, Nobuko,Watanabe, Toshiaki,Ishibashi, Akira,Yuki, Satoshi,Tanaka, Masahiko
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p. 1478 - 1483
(2008/09/18)
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- PYRAZOLE DERIVATIVES AS CBl MODULATORS
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The present invention relates to compounds of formula (I) wherein R1 represents a group R5O- in which R5 represents a C3-7alkyl group substituted by one or more fluoro or R5 represents a C3-7alkylsulphonyl group which is optionally substituted by one or more fluoro; R2 represents a C1-4alkyl group, hydroxy, fluoro, chloro or cyano wherein each R2 is independently selected when n is >1; R3 represents a) cyclohexyl optionally substituted by one or more of the following: hydroxy, fluoro, amino, mono or diC1-3alkylamino, carboxy or a C1-4alkoxycarbonyl group b) piperidino substituted by one or more hydroxy c) unsubstituted piperidino but only when one of the following applies: R4 represents cyano or R1 represents 3-fluoropropylsulphonyloxy or R1 represents 3,3,3-trifluoropropoxy or R1 represents 3-fluoropropoxy or R2 is methyl d) phenyl substituted by one or more of the following: hydroxy, halo or a C1-4alkyl group e) pyridyl substituted by a C1-4alkyl group or f) a C4-9alkyl group; R4 represents cyano or methyl; and n is 1, 2 or 3 and pharmaceutically acceptable salts thereof and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 32
(2010/11/25)
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- PYRAZOLE DERIVATIVES AS THERAPEUTIC AGENTS
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Salts of 1,5-diarylpyrazole-3-carboxamides and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 35; 54
(2010/11/26)
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- Asymmetric synthesis, crystal structure, and antidepressant activity of 2-aryl-3-alkyl-5-methyl-2-morpholinol hydrochlorides
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2-Aryl-3-alkyl-5-methyl-2-morpholinols were synthesized from the reactions of chiral 2-aminopropan-1-ol with 2-bromo-1-phenylpropan-1-one, 2-bromo-1-(3-chlorophenyl)propan-1-one, 1-(4-(benzyloxy)phenyl)-2-bromopropan1- one, 2-bromo-1-(6-methoxy- naphthalen-2-yl)propan-1-one, and 1-(4-(benzyloxy)phenyl)pentan-1-one in N-methyl-2-pyrrolidone (NMP), respectively. The 2-aryl-3-alkyl-5-methyl-2-morpholinols were reacted with hydrogen chloride to give the hydrochloride salts with yields of 56%-77%. The structures of the products were proven by means of their 1H NMR, IR, and MS spectroscopic data. The stereochemical properties of representative products were established unambiguously by the X-ray single crystal analysis. The antidepressant activities of the title compounds were assayed by the mouse forced swimming test (FST). The FST results confirm the antidepressant properties of our products.
- Cao, Gao,Hu, Ai-Xi,Xiao, Xin-Rong
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- Synthesis and evaluation of uterine relaxant activity for a novel series of substituted p-hydroxyphenylethanolamines
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Novel racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]aminopropan-1-ol hydrochlorides (9a-h) were synthesized by condensing racemic 1-(p-hydroxyphenyl)-2-aminopropan-1-ol hydrochloride (6) with substituted aryloxymethyloxiranes (8a-h) in DMF in presence of anhydrous potassium carbonate and then reacting with dry hydrogen chloride gas. They were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP releasing potential was studied using rat uterus tissue homogenates by cAMP [3H] assay and cardiac stimulant potential was evaluated in dog. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP releasing potential was higher than isoxsuprine hydrochloride except for 9b and 9c. Finally insignificant cardiac stimulant potential was noted for these compounds when compared to isoxsuprine hydrochloride.
- Viswanathan,Chaudhari
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p. 6581 - 6585
(2007/10/03)
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- THERAPEUTIC AGENTS
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The present invention relates to 1,5-diphenylpyrazole compounds of formula I (A chemical formula should be inserted here - please see paper copy enclosed herewith) and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 38; 39
(2008/06/13)
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- Design, synthesis and evaluation of racemic 1-(4-hydroxyphenyl)-2-[3- (substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides as novel uterine relaxants
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Novel 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl] amino-1-propanol hydrochlorides were designed based on the pharmacophore for potent uterine relaxant activity and by utilizing the principles of structural hybridization. The designed molecules were synthesized as racemates by a novel route and were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP-releasing potential was studied using rat uterus tissue homogenates by the cAMP [3H] assay, and cardiac stimulant potential was evaluated on isolated guinea pig right atrium. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP-releasing potential was slightly less, while their cardiac stimulant potential was insignificant as compared to isoxsuprine hydrochloride.
- Viswanathan,Kodgule,Chaudhari
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p. 3532 - 3535
(2007/10/03)
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- THERAPEUTIC AGENTS
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The present invention relates to compounds of formula (I) and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 20; 36-37
(2008/06/13)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE s-AMINO ALCOHOL
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A process for easily producing an optically active β-amino alcohol useful as a pharmaceutical intermediate from an inexpensive, readily available starting material is provided. A readily available α-substituted ketone is reacted with an optically active amine to yield a diastereomer mixture of an optically active α-substituted aminoketone. One of the diastereomers is isolated optionally after the diastereomers are converted to salts with an acid. The optically active α-substituted aminoketone or a salt thereof thus isolated was stereoselectively reduced to yield an optically active β-substituted amino alcohol. The optically active β-substituted amino alcohol is subjected to hydrogenolysis to produce an optically active β-amino alcohol or a salt thereof.
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(2008/06/13)
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- Pyrrole derivatives and medicinal composition
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The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.
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- A facile synthesis of 2-hydroxy-2-aryl 1,4-benzodioxanes
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Condensation of catechol with 2-bromo-1-aryl-ethanones and 2-bromo-1- aryl-propanones in dry acetone-K2CO3 medium afforded 2-hydroxy-2-aryl-1,4- benzodioxanes in good yield.
- Ganesh,Harish Kumar,David Krupadanam
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p. 2069 - 2078
(2007/10/03)
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- ARYLOXY-ALKYL-DIALKYLAMINES
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The present invention provides compounds useful in the synthesis of biologically active compounds, and processes for their production, the compounds having the formula: STR1 wherein: R 1 and R 2 are, independently, selected from H; C 1-C 12 alkyl or C 1-C. sub.6 perfluorinated alkyl; X represents a leaving group; A is O or S; m is an integer from 1 to 3, preferably 2; R 3, R 4, R 5, and R. sup. 6 are independently selected from H, halogen,--NO. sub.2, alkyl, alkoxy, C 1-C 6 perfluorinated alkyl, OH or the C. sub.1-C 4 esters or alkyl ethers thereof,--CN,--O--R 1,--O--Ar,--S--R. sup.1,--S--Ar,--SO--R 1,--SO--Ar,--SO 2--R 1,--SO. sub. 2--Ar,--CO--R 1,--CO--Ar,--CO 2--R 1, or--CO 2--Ar; and Y is selected from a) the moiety: STR2 wherein R. sub.7 and R 8 are independently selected from the group of H, C 1-C. sub.6 alkyl, or phenyl; or b) an optionally substituted five-, six-or seven-membered saturated, unsaturated or partially unsaturated heterocycle or bicyclic heterocycle containing up to two heteroatoms selected from the group consisting of--O--,--NH--,--N(C 1 C 4 alkyl)--,--N=, and--S(O). sub.n--.
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- 2-PIPERIDINO-1-ALKANOL DERIVATIVES AS NEUROPROTECTIVE AGENTS
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A method of blocking N-methyl-D-aspartic acid (NMDA) receptor sites in a mammal in need thereof with an effective NMDA blocking (neuroprotective and antiischemic) amount of 2-piperidino-1-alkanol derivatives and 2-azabicyclo-1-alkanol derivatives and analogs and pharmaceutically acceptable salts thereof; methods of using these compounds in the treatment of stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised.
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- Nortropyl-1-alkanol derivatives as antiischemic agents
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2-(8-Azabicyclo[3.2.1]oct-8-yl)alkanols of the formula STR1 wherein Q is S or CH=CH; X is H, OH or another aromatic substituent; R is hydrogen, alkyl, alkenyl or alkynyl; Y and Y1 are taken together and are arylmethylene or aralkylmethylene (or a corresponding epoxy derivative) or Y and Y1 are taken separately and Y is hydrogen or OH, and Y1 is aryl, aralkyl, arylthio, or aryloxy; and structurally related 2-(piperidino)alkanols; pharmaceutical compositions thereof; methods of treating CNS disorders therewith; and intermediates useful in the preparation of said compounds.
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