- Synthesis of Novel Aryloxyethylamine Derivatives and Evaluation of Their in Vitro and in Vivo Neuroprotective Activities
-
A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by 1H-NMR, 13C-NMR, FT-IR and HR-ESI-MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti-ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate-induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone, (4-bromophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, (4-chlorophenyl)(1-{2-[(naphthalen-2-yl)oxy]ethyl}piperidin-4-yl)methanone, (4-chlorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone and {1-[2-(4-bromophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 μM). Compounds (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, (4-fluorophenyl){1-[2-(naphthalen-2-yloxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti-ischemic stroke agents. Basic structure–activity relationships are also presented.
- Gao, Yarong,Qi, Changyong,Wu, Bin,Xu, Yi,Zhong, Yan
-
-
- 1-aryloxy ethyl piperidine-4-yl benzophenone derivative as well as preparation method and application thereof
-
The invention discloses a 1-aryloxy ethyl piperidine-4-yl benzophenone derivative as well as a preparation method and application thereof. The compound is a free alkali or salt with a compound of a formula (I) shown in the specification; the salt is one of hydrochloride, hydrobromide, sulfate, trifluoroacetate, tartrate, lactate or mesylate; in the formula, R1 independently represents H, halogen,alkyl, halogen-substituted alkyl, nitryl, amino, nitrile, hydroxyl, alkoxy, aryl alkoxy, heterocyclic alkoxy, aryl, substituted heterocyclic ring or substituted aryl; and R2 is independently selectedfrom H, halogen, alkyl, halogen substituted alkyl, nitryl, amino, nitrile, hydroxyl, alkoxy, aryl alkoxy, heterocyclic alkoxy, aryl, substituted heterocyclic ring or substituted aryl. The 1-aryloxy ethyl piperidine-4-yl benzophenone derivative is applied to preparation of medicines for treating cerebral arterial thrombosis.
- -
-
-
- Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors
-
Regulation of glycine transporter 1 (GlyT1) activity is a currently investigated strategy in drug discovery for schizophrenia. This study developed a series of new 4-benzoylpiperidine derivatives as GlyT1 inhibitors by bioisosteric replacement and mimicking of the pyridine ring of RG1678. Among the 4-benzoylpiperidine derivatives, 23q showed an IC50 of 30 nM. Preliminary optimization of the blood-brain barrier penetration led to the discovery of 3-(piperidin-4-yl)benzo[d]isoxazole derivatives. Both series showed good selectivity over GlyT2, D1, D2, D3, 5-HT1A and 5-HT2A receptors. Moreover, behavioral testing showed 23q (40 mg kg-1, intragastric) can inhibit the hyperlocomotion induced by acute treatment of phencyclidine, and improve the impaired negative and cognitive symptoms in chronic phencyclidine-induced C57BL/6J mice. An interesting finding showed that 3-(piperidin-4-yl)benzo[d]isoxazole was a privileged scaffold of atypical antipsychotic agents but exhibited high selectivity and potency as a GlyT1 inhibitor.
- Liu, Yang,Guo, Lin,Duan, Hongliang,Zhang, Liming,Jiang, Neng,Zhen, Xuechu,Shen, Jianhua
-
p. 40964 - 40977
(2015/05/20)
-
- METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0409; 0410
(2015/04/21)
-
- METHYLENE LINKED QUINOLINYL MODULATORS OF ROR-GAMMA-T
-
The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Page/Page column 115
(2015/05/05)
-
- METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt
-
The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0479; 0480
(2014/05/07)
-
- DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS
-
The present invention relates to derivatives of general formula I wherein : - W represents nitrogen, - R1 represents: ? a hydrogen or a linear or branched C1-C5 alkyl radical or, ? a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, ? a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, ? a C6 2-oxocycloalkyl radical - R2 represents a methyl or heptyl, - m, n are equal to 1, - V represents CH2, - X-Y represents -N- (C=O) -, -CH-O-, - Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.
- -
-
Page/Page column 32-33
(2010/04/03)
-
- Syntheses and Binding Studies of New [(Aryl)(aryloxy)methyl]piperidine Derivatives and Related Compounds as Potential Antidepressant Drugs with High Affinity for Serotonin (5-HT) and Norepinephrine (NE) Transporters
-
In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT1A and 5-HT2A receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT 1A and 5-HT2A receptors. Some of these racemic mixtures were resolved to their enantiomers and tested for binding to norepinephrine (NE) transporter (NET), dopamine (DA) transporter (DAT), and α2 receptor. Several of these enantiomers [(-)-15b, (-)-15j, (-)-15t, (+)-15u] displayed a dual binding profile with affinities for SERT and NET with K i i = 1.9 and 13.5 nM, respectively), and further pharmacological characterization is in progress for its evaluation as a antidepressant.
- Orjales, Aurelio,Mosquera, Ramón,Toledo, Antonio,Pumar, M. Carmen,García, Neftalí,Cortizo, Lourdes,Labeaga, Luis,Innerárity, Ana
-
p. 5512 - 5532
(2007/10/03)
-
- Subtype-selective NMDA receptor ligands and the use thereof
-
The invention relates to subtype-selective NMDA receptor ligands and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neuro-degenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, Parkinson's disease, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition.
- -
-
-
- 4-substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists
-
PCT No. PCT/US96/20872 Sec. 371 Date Sep. 16, 1998 Sec. 102(e) Date Sep. 16, 1998 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/23216 PCT Pub. Date Jul. 3, 1997Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs are selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described.
- -
-
-
- (Aryl(alkyl)carbonyl)-heterocyclic compounds, compositions and use
-
The invention relates to a compound selected from those of formula (I): STR1 wherein Ar, n, B and A are as defined in the description, to their optical isomers, and to their addition salts there of with a pharmaceutically-acceptable acid or base. Medicinal product which is useful for treating pain and treating or preventing pathologies which require psychotropic agents.
- -
-
-
- 7-fused 2-(piperazinoalkyl) indole derivatives, intermediates and compositions thereof
-
Pharmacologically active compounds having anti-allergic properties corresponding to the formula I STR1 which can be mono- or disubstituted in the phenyl ring and their acid addition salts and/or S-mono- or dioxides of sulfur-containing compounds of the formula I are described, together with processes and intermediates for their preparation.
- -
-
-
- Aryl(alkyland alkylene)-N-((phenoxy and phenylthio)alkyl) aminoheterocyclics as cardiovascular, anthihistaminic, antisecretory and antiallergy agents
-
A method of treating cardiac dysfunction, the effects of histamine, and gastric secretion excesses with aryl(alkyl and alkylene)-N-[(phenoxy and phenythio)alkyl]aminoheterocyclics corresponding to the formula: STR1 wherein Ar is phenyl or substituted phenyl; R is phenyl, substituted phenyl, pyridinyl or cycloalkyl; A is hydrogen, hydroxy, cyano, amido and amino; Q is --CH2 --, --CH--, or --CHOH--; d and n are zero or one and the dotted lines form double bonds consistent with the valence of carbon; p is zero, one or two; m is one to six inclusive; B is oxygen, nitrogen, sulfur, sulfinyl or sulfonyl; z is zero or one; l is zero or one; W is hydrogen, loweralkyl, halo, nitro, loweralkoxy or hydroxy; X is hydrogen, loweralkyl, halogen, loweralkoxy or hydroxy; Y is --CH(OH)CH2 OH, --CH(OH)C(O)OH, --C(O)C(O)OH, --C(O)CH2 OH,--C(O)C(O)OCH3, --C(O)C(O)OC2 H5, --CH2 C(O)OC2 H5, --CH(OH)C(O)OCH3, --CH(OH)C(O)OC2 H5 or --C(O)CH2 OC(O)CH3 ; and the pharmaceutically acceptable salts thereof; in addition to the above methods of treatment, compounds wherein (B)z is oxygen are useful in a method of treating Gell and Coombs type 1 allergic responses in mammals.
- -
-
-
- Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a method for allergy treatment
-
A method of inhibiting Type 1 allergic responses in a living animal body with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain known compounds: STR1 wherein P is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, CH2 -- or STR2 n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the α carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one,4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one, 1,4-benzodioxanloweralkyl-2-yl or 1,1'-biphenyl-4-yl and the pharmaceutically acceptable salts thereof.
- -
-
-
- 4-[(α,α-diaryl)-hydroxymethyl]-1-piperidinylalkyl-cyclic carbamate derivatives as allergic response inhibitors
-
4-[(α,α-Diaryl)-hydroxymethyl]-1-piperidinylalkylcyclic carbamate derivatives having the formula: STR1 wherein; R is hydrogen, loweralkyl, cycloalkyl, phenyl and substituted phenyl; Ar and Ar1 are phenyl, substituted phenyl or pyridinyl; alk is a straight or branched hydrocarbon chain; R1 is loweralkyl substituted for hydrogen on a ring carbon. The compounds are useful antihistamines and in controlling allergic response.
- -
-
-
- 1,5-Disubstituted-1,2-dihydro-2H-1,4-benzodiazepin-2-ones
-
1,5-Disubstituted-1,2-dihydro-2H-1,4-benzodiazepin-2-ones of the formula STR1 wherein R is hydrogen or fluoro, R1 is hydrogen, fluoro chloro, bromo or trifluoromethyl, and n is 2 to 4, having anticonvulsant activity and useful as anti-anxiety agents, are disclosed.
- -
-
-
- Benzoylpiperidylalkylindoles
-
New benzoylpiperidylalkylindoles and related compounds possessing tranquilizing, anti-hypertensive and analgesic properties and a process for the preparation thereof are described.
- -
-
-