- SUBSTITUTED ARYLUREA COMPOUNDS FOR INDUCING APOPTOSIS AND COMPOSITION FOR ANTICANCER COMPRISING THE SAME
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The present invention relates to a substituted arylurea compound inducing apoptosis and an anticancer composition comprising the same. The present invention relates to a novel compound capable of preventing, treating and alleviating cancer diseases such as prostate cancer, breast cancer, lung cancer, colorectal cancer, and skin cancer by inhibiting apoptosis of cancer cells and inhibiting proliferation of cancer cells.
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- Synthetic method of venlafaxine hydrochloride intermediate
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The invention provides a synthetic method of a venlafaxine hydrochloride intermediate, the venlafaxine hydrochloride intermediate is a compound 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol as shown in a formula I. The method comprises the following steps: carrying out hydrogenation catalytic reaction on a compound 1-cyano-(4-methoxyphenyl) methyl cyclohexanol as shown in a formula II as a raw material; and carrying out hydrogenation catalytic reaction by adopting a copper-nickel catalyst to obtain the compound as shown in the formula I. The venlafaxine hydrochloride produced by the method can effectively control the generation of impurities, and the yield and the purity of the compound shown in the formula I are improved.
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Paragraph 0023; 0025; 0027; 0029; 0031; 0033; 0035-0036
(2021/06/02)
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- Preparation method of venlafaxine impurity E (by machine translation)
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The invention belongs to the technical field of organic synthesis, and relates to a preparation method of venlafaxine impurity E, which comprises (1) a condensation reaction, (2) a reduction reaction and (3) a ring-forming reaction. The method for synthesizing venlafaxine impurity E is less in steps, high in product purity, safe in reaction, less in waste liquid, simple in post-treatment, convenient to operate and convenient for industrial production. (by machine translation)
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- A method for the preparation of venlafaxine hydrochloride (by machine translation)
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The invention discloses a method for the preparation of venlafaxine hydrochloride. The method is provided with the screen of the Raney nickel catalyst in the micro-reactor, at a temperature of 20 - 40 °C lower, compound I with the hydrogen reaction to obtain compound II; compound II by adding sulfuric acid to form the salt to obtain the target product 1 - [2 - amino - 1 - (4 - methoxyphenyl) ethyl] cyclohexanol sulfate (compound III). The present invention provides a micro-reactor on the basis of the Raney nickel sieve catalyst of the creativity of the card in the pipe joint, the catalytic effect is enhanced, and the catalyst can be recycled, at the same time avoid the catalyst mixed in the feed liquid to the micro-reactor slurry pump damage and to avoid reaction of the pipeline blockage. (by machine translation)
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Paragraph 0031-0033; 0035-0037
(2017/07/19)
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- Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis
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Elevated activity of methionyl-tRNA synthetase (MRS) in many cancers renders it a possible drug target in this disease area, as well as in a series of parasitic diseases. In the present work, we report the synthesis and in vitro screening of a library of 1,3-oxazines, benzoxazines and quinoline scaffolds against human MRS. Among the compounds tested, 2-(2-butyl-4-chloro-1-(4-phenoxybenzyl)-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane (compound 21) and 2-(2-butyl-4-chloro-1-(4-nitrobenzyl)-1H-imidazol-5-yl)-2,4-dihydro-1H-benzo[d][1,3]oxazine (compound 8) were found to be potent inhibitors of MRS. Additionally, these compounds significantly suppressed the proliferation of A549 and HCT116 cells with IC50 values of 28.4, 17.7, 41.9, and 19.8 μM respectively. Molecular docking studies suggested that the ligand binding orientation overlaps with the original positions of both methionine and adenosine of MRS. This suggests the binding of compound 21 against MRS, which might lead the inhibitory activity towards cancer cells.
- Bharathkumar, Hanumantharayappa,Mohan, Chakrabhavi Dhananjaya,Rangappa, Shobith,Kang, Taehee,Keerthy,Fuchs, Julian E.,Kwon, Nam Hoon,Bender, Andreas,Kim, Sunghoon,Basappa,Rangappa, Kanchugarakoppal S.
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p. 9381 - 9387
(2015/09/15)
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- DERIVATIVES OF (-)-VENLAFAXINE AND METHODS OF PREPARING AND USING THE SAME
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Methods of preparing, and compositions comprising, derivatives of (?)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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- An improved and impurity-free large-scale synthesis of venlafaxine hydrochloride
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An improved and impurity-free synthetic method for large-scale synthesis of venlafaxine hydrochloride was developed using inexpensive reagents. The overall yield obtained from this newly developed process is 55% in a highly pure state with >99.9% purity by HPLC.
- Saravanan, Mohanarangam,Satyanarayana, Bollikonda,Reddy, Padi Pratap
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p. 1392 - 1395
(2012/01/13)
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- A PROCESS FOR PREPARATION OF PHENETHYLAMINE DERIVATIVE
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The present invention relates to a process for the preparation of 1-[2-amino-1-(4-substituted phenyl)ethyl]cyclohexanol (3) (where R is OMe, OH), said process comprising the steps of; subjecting a reaction mixture of substituted phenylacetonitrile (2) in alcohol, an organic acid, and a hydrogenating catalyst in the presence of hydrogen gas pressure in the range of 0.5 kg/cm2 to 30 kg/cm2 and temperature in the range of 0-100°C; filtering and concentrating the cooled reaction mixture to obtain an acid addition salt of 1-[2-amino-1-(4-substituted phenyl)ethyl]cyclohexanol (4); and treating the acid addition salt of 1-[2-amino-1-(4-substituted phenyl)ethyl]cyclohexanol (4) with an ester in presence of a base to obtain 1-[2-amino-1-(4-substituted phenyl) ethyl] cyclohexanol (3).
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Page/Page column 12
(2010/09/18)
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- PROCESS FOR THE PREPARATION OF PHENETHYLAMINE DERIVATIVES
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The present invention relates to an improved process for the preparation of essentially pure Venlafaxine Hydrochloride. Particularly, the process for the preparation of Venlafaxine Hydrochloride comprises the following steps: i) Preparation of 1-[Cyano-1-(4-methoxyphenyl)methyl]cyclohexanol, ii) Preparation of crude Venlafaxine Hydrochloride by reduction of 1-[Cyano-1-(4-methoxyphenyl)methyl]cyclohexanol with Alkali metal borohydride and Lewis acid and subsequent conversion to Venalfaxine hydrochloride with formic acid and paraformaldehyde and finally iii) Purification of crude Venlafaxine Hydrochloride.
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Page/Page column 4
(2010/04/30)
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- A PROCESS FOR THE PREPARATION OF VENLAFAXINE HYDROCHLORIDE
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The present invention relates to a process for the preparation of Venlafaxine Hydrochloride comprising steps of i) treating 4-methoxyphenyl acetonitrile with cyclohexanone in presence of alkali hydroxide and super base to get 1-[cyano (4-methoxyphenyl) methyl] cyclohexanol and ii) reducing 1-[cyano (4-methoxyphenyl) methyl] cyclohexanol in presence of catalyst, activator and alcoholic ammonia under hydrogen pressure.
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Page/Page column 11-12
(2010/05/13)
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- SOLID FORMS COMPRISING (-) O-DESMETHYLVENLAFAXINE AND USES THEREOF
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Solid forms comprising a compound useful in the treatment, prevention and management of various conditions and diseases are provided herein. In particular, the invention provides solid forms comprising (-)-O-desmethylvenlafaxine, including salts thereof, having utility for the treatment, prevention and management of conditions and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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- Processes for the synthesis of O-desmethylvenlafaxine
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The present invention describes processes for the preparation of O-desmethylvenlafaxine and tridesmethylvenlafaxine, which may be used as an intermediate in preparing O-desmethylvenlafaxine.
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Page/Page column 5
(2008/12/06)
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- IMPROVED PROCESS FOR THE PREPARATION OF PHENETHYLAMINE DERIVATIVES
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The present invention relates to an improved process for the preparation of essentially pure Venlafaxine Hydrochloride. Particularly, the process for the preparation of Venlafaxine Hydrochloride comprises the following steps: i) Preparation of l-[Cyano-l- (4-methoxyphenyl) methyl] cyclohexanol, ii) Preparation of crude Venlafaxine Hydrochloride by reduction of l-[Cyano-l-(4-methoxyphenyl) methyl] cyclohexanol with Alkali metal borohydride and Lewis acid and subsequent conversion to Venalfaxine hydrochloride with formic acid and paraformaldehyde and finally iii) Purification of crude Venlafaxine Hydrochloride.
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Page/Page column 7-8
(2008/12/07)
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- Process for preparation of o-desmethylvenlafaxine and its analogue
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The present invention belongs to the field of organic chemistry and refers to a process for the preparation of O-desmethylvenlafaxine (1-[2-Dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol) and its analogues. The invention also relates to a catalytic hydrogenation of cyano-group of the substituted acetonitrile.
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Page/Page column 8
(2008/06/13)
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- PROCESS FOR PREPARATION OF 0-DESMETHYLVENLAFAXINE AND ITS ANALOGUES
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The present invention belongs to the field of organic chemistry and refers to a process for the preparation of O-desmethylvenlafaxine (l-[2-Dimethylamino)-l-(4-hydroxyphenyl)ethyl]cyclo- hexanol), its analogues and pharmaceutical acceptable salts thereof. The invention also relates to a catalytic hydrogenation of cyano-group of the substituted acetonitrile.
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Page/Page column 12-13
(2008/06/13)
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- A NOVEL PROCESS FOR PREPARATION OF VENLAFAXINE HYDROCHLORIDE AND ITS INTERMEDIATES
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A process for the preparation of 1-cyano-[(4-methoxyphenyl)methyl] cyclohexanol by reacting cyclohexanone with the carbanion of 4-methoxyphenyl acetonitrile in the presence of polyethylene glycol-400 (PEG-400) or Aliquate-336, as a phase transfer catalyst (PTC). The present invention also relates to an novel process for the preparation of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol, using borane-dimethyl sulphide complex (BDMS) or AlCl3-NaBH4, in refluxing tetrahydrofuran. 1-[2-Amino-1-(4-methoxyphenyl)ethyl]cyclohexanol thus obtained was subjected to N,N-dimethylation using formic acid-formaldehyde in boiling 1,4-dioxane: water mixture to obtain 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol in high purity, which was treated with isopropanol saturated with HCl gas to get venlafaxine hydrochloride in high purity and high yield.
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Page/Page column 7-8
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF HIGHLY PURE 1-[2-DIMETHYLAMINO-(4-METHOXYPHENYL) ETHYL]CYCLOHEXANOL HYDROCHLORIDE
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The invention encompasses processes for the preparation of highly pure venlafaxine hydrochloride, l-[2-dimethylamino-(4-methoxyphenyl)ethyl]cyclohexanol hydrochloride as well as intermediates thereof.
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Page/Page column 17; 18; 19; 20
(2010/11/27)
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- AN IMPROVED PROCESS FOR PRODUCTION OF INTERMEDIATE OF ANTIDEPRESSANT AGENT
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The present invention discloses a process for the preparation of substituted aryl alkylamine compounds comprising the steps of, reducing the substituted aryl acetonitrile substrate using Raney nickel catalyst at lower substrate/catalyst ratio of 20: 1 to 6: 1 with higher substrate concentration, at ramped temperature / pressure profile, in the presence of an alcoholic solvent selected from C1 to C4 alcohol and isolating the corresponding substituted phenyl ethylamine as a suitable salt.
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Page/Page column 8-10
(2008/06/13)
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- Process for the preparation of phenethylamine derivative, an intermediate of Venlafaxine hydrochloride
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The present invention relates to an improved process for the preparation of phenethylamine derivatives or salts by hydrogenation of phenylacetonitriles in the presence of heterogeneous palladium on carbon catalyst.
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Page/Page column 3
(2010/02/10)
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- Synthesis and molecular structure analysis of venlafaxine intermediate and its analog
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1-(cyano-(4-methoxyphenyl) methyl cyclohexanol (2), C24U 32N2O2, a Venlafaxine intermediate is found to crystallize in both monoclinic (2a) and orthorhombic (2b) crystal systems. The form 2a crystallizes in the space group C2/c with the cell parameters a = 23.506(3), b = 5.550(3), c = 23.192(3), and β = 115.116(2)°. 2b crystallizes in space group P212121 with cell parameters α = 5.7850(6), b = 11.2680(6), and c = 20.6730(19). The intermolecular hydrogen bonding in the case of the monoclinic polymorph leads to the formation of dimer. The synthesis, characterization, and crystal structure studies of Venlafaxine analog 1-[2-1-(4-dimethylamino-phenyl)-ethylideneamino]- 1-(4-methoxyphenyl)-ethyl]-cyclohexanol (4) is reported. 4 crystallizes in P1 space group with cell parameters a = 10.801(7), b = 12.078(7), c = 9.928(5), α = 96.12(5)°, β = 110.49(5)°, and γ = 112.42(6)°.
- Kavitha,Lakshmi,Basappa,Mantelingu,Sridhar,Shashidhara Prasad,Rangappa
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p. 957 - 963
(2007/10/03)
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- Derivatives of venlafaxine and methods of preparing and using the same
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Methods of preparing, and compositions comprising, derivatives of venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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- Simple and an efficient method for the synthesis of 1-[2-dimethylamino-1- (4-methoxy-phenyl)-ethyl]-cyclohexanol hydrochloride: (±) venlafaxine racemic mixtures
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A novel synthetic method was developed for the synthesis of venlafaxine using inexpensive reagents. An improvement in the method, in the yield was achieved for the conversion of the venlafaxine. This is an improved version, simple and efficient method for the large-scale synthesis of venlafaxine.
- Basappa,Kavitha,Rangappa
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p. 3279 - 3281
(2007/10/03)
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- An efficient and green protocol for the preparation of cycloalkanols: A practical synthesis of venlafaxine
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The condensation of arylacetonitriles with cyclic ketones using aqueous NaOH or KOH under phase transfer catalysis gives almost quantitative yields of cycloalkanols. This protocol is utilized for a practical synthesis of the antidepression drug, venlafaxine 1.
- Chavan, Subhash P.,Khobragade, Dushant A.,Kamat, Subhash K.,Sivadasan, Latha,Balakrishnan, Kamalam,Ravindranathan,Gurjar, Mukund K.,Kalkote, Uttam R.
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p. 7291 - 7295
(2007/10/03)
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- Process for preparation of phenethylamine derivatives
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A process for the preparation of a compound of formula I, wherein R1 and R2 are ortho or para substituents, independently selected from the group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C7-C9 aralkoxy, C2-C7 alkanoyloxy, C1-C6 alkylmercapto, halo and trifluoromethyl; R3 is hydrogen or C1-C6 alkyl ; R4 is hydrogen, C1-C6 alkyl, formyl or C2-C7 alkanoyl; n is one of the integers 0, 1, 2, 3 or 4; and the dotted line represents optional olefinic unsaturation; comprising hydrogenating a compound of formula III, in the presence of a nickel or cobalt catalyst at a temperature of about 5° C. to 25° C.
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- Derivatives of (?)-venlafaxine and methods of preparing and using the same
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Methods of preparing, and compositions comprising, derivatives of (?)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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- Intermediate for the production of 1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]-cyclohexanol
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Processes for the preparation of Venlafaxine (IX) via the novel epoxy-nitrile intermediate (I), which when subjected to hydrogenation forms compound (X), and may subsequently be reduced to yield the desired product (IX). The epoxy-nitrile intermediate (I) itself may be synthesised via various alternative reaction strategies, from a range of starting materials. E.g. 4-methoxy-benzaldehyde (VI), upon treatment with cyclohexyl magnesium bromide yields compound (V). This in turn may be oxidised to yield compound (III), which forms compound (II) on treatment with an α-keto-halogenation agent. Cyanation of compound (II), then yields the desired epoxy nitrile intermediate (I), from which Venlafaxine (IX) may be synthesised.
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- Derivatives of (+)-venlafaxine and methods of preparing and using the same
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Methods of preparing, and compositions comprising, derivatives of (+)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.
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- 2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: Synthesis and antidepressant activity
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A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models - the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.
- Yardley,Morris Husbands,Stack,Butch,Bicksler,Moyer,Muth,Andree,Fletcher III,James,Sielecki
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p. 2899 - 2905
(2007/10/02)
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- 2-PHENYL-2-(1-HYDROXYCYCLOALKYL OR 1-HYDROXYCYCLOALK-2-ENYL)ETHYLAMINE DERIVATIVES
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This invention provides a group of hydroxycycloalkanephenethyl amine antidepressant derivatives of the following structural formula: STR1 in which A is a moiety of the formula STR2 where the dotted line represents optional unsaturation;R 1 is hydrogen or alkyl;R 2 is alkyl;R. sub.4 is hydrogen, alkyl, formyl or alkanoyl;R 5 and R 6 are, independently, hydrogen, hydroxyl, alkyl, alkoxy, alkanoyloxy, cyano, nitro, alkylmercapto, amino, alkylamino, dialkylamino, alkanamido, halo, trifluoromethyl or, taken together, methylenedioxy;R. sub.7 is hydrogen or alkyl; andn is 0, 1, 2, 3 or 4;or a pharmaceutically acceptable salt thereof.
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