WO2010059844A1 - Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof - Google Patents
Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof Download PDFInfo
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- WO2010059844A1 WO2010059844A1 PCT/US2009/065173 US2009065173W WO2010059844A1 WO 2010059844 A1 WO2010059844 A1 WO 2010059844A1 US 2009065173 W US2009065173 W US 2009065173W WO 2010059844 A1 WO2010059844 A1 WO 2010059844A1
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4462—Non condensed piperidines, e.g. piperocaine only substituted in position 3
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Definitions
- Nicotinic acetylcholine receptors form a family of ion channels activated by acetylcholine. Functional receptors contain five subunits and there are numerous receptor subtypes. Studies have shown that central nicotinic acetylcholine receptors are involved in learning and memory. Nicotinic acetylcholine receptors of the alpha7 subtype are prevalent in the hippocampus and cerebral cortex.
- WO 2003/055878 describes a variety of agonists of the alpha7 nAChR said to be useful for improving cognition.
- WO 2003/055878 suggests that certain agonists of the alpha7 nAChR are useful for improving perception, concentration, learning or memory, especially after cognitive impairments like those occurring for example in situations/diseases/syndromes such as mild cognitive impairment, age-associated learning and memory impairments, age-associated memory loss, Alzheimer's disease, schizophrenia and certain other cognitive disorders.
- the compounds described are (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2- carboxamide and pharmaceutically acceptable salts thereof.
- Alzheimer's disease schizophrenia and other disorders such as other neurodegenerative diseases (e.g., Huntington's Disease or Parkinson's Disease) and attention deficit disorder. It can be used treat certain disorders, e.g., Alzheimer's disease, schizophrenia (e.g., paranoid type, disorganized type, catatonic type, and undifferentiated type), schizophreniform disorder, schizoaffective disorder, delusional disorder, positive symptoms of schizophrenia, negative symptoms of schizophrenia at a daily dose of 3 mg, 2.70 mg, 2.50 mg, 2.25 mg, 2 mg, 1.75 mg, 1.50 mg, 1.25 mg, 1 mg, 0.7, 0.5, 0.3 mg or even 0.1 mg.
- the compound can be used to improve one or more aspects of cognition, e.g., one or more of: executive function, memory (e.g., working memory), social cognition, visual learning, verbal learning and speed of processing.
- the treatment can improve one or more facets of cognition (e.g., visual motor skill, learning, delayed memory, attention, working memory, visual learning, speed of processing, vigilance, verbal learning, visual motor function, social cognition, long term memory, executive function, etc.).
- the methods can be used to treat: Alzheimer's disease, schizophrenia (e.g., paranoid type, disorganized type, catatonic type, and undifferentiated type), schizophreniform disorder, schizoaffective disorder, delusional disorder, positive symptoms of schizophrenia or negative symptoms of schizophrenia.
- schizophrenia e.g., paranoid type, disorganized type, catatonic type, and undifferentiated type
- Dose is the amount of active pharmaceutical ingredient (API) administered to a patient.
- API active pharmaceutical ingredient
- 1 mg dose means 1 mg of API was administered to each patient each day.
- Active Pharmaceutical Ingredient is defined as either (R)-7-chloro-N-(quinuclidin-3- yl)benzo[b]thiophene-2-carboxamide hydrochloride, (R)-7-chloro-N-(quinuclidin-3- yl)benzo[b]thiophene-2-carboxamide, (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2- carboxamide hydrochloride monohydrate or (R)-7-chloro-N-(quinuclidin-3- yl)benzo[b]thiophene-2-carboxamide hydrochloride solvate.
- solvate represents a stoichiometric ratio of 0.1 to 10 molecules of solvent compared to (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride or (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide.
- Solvent molecules include but are not limited to water, methanol, 1,4 dioxane, ethanol, iso-propanol or acetone. In some cases water is the preferred solvate.
- "The test compound” is defined as (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene- 2-carboxamide hydrochloride.
- ECR is the concentration of drug which elicits equal response in oocytes transfected with cloned human alpha7 receptor at 50 ⁇ M acetylcholine. Maximum stimulation of the cloned human alpha 7 receptor occurs at a concentration >250 ⁇ M of acetylcholine.
- FIGURE 1 depicts the results of a study on the effect of the test compound on P50 gating.
- the standard errors of each mean are noted in the legend.
- the bars (left to right) represent placebo, 0.3 mg test compound, and 1.0 mg test compound.
- the standard errors of each mean are noted in the legend.
- the bars left to right represent placebo, 0.3 mg test compound, and 1.0 mg test compound.
- FIGURE 2 depicts the results of a study on the effect of the test compound on PlOO gating.
- the standard errors of each mean are noted in the legend.
- the bars left to right represent placebo, 0.3 mg test compound, and 1.0 mg test compound
- the standard errors of each mean are noted in the legend.
- the bars left to right represent placebo, 0.3 mg test compound, and 1.0 mg test compound.
- FIGURE 3 depicts that results of a study on the effect of the test compound on MMN amplitude and POO amplitude.
- the standard errors of each mean are noted in the legend.
- the bars left to right represent placebo, 0.3 mg test compound, and 1.0 mg test compound.
- the standard errors of each mean are noted in the legend.
- the bars left to right represent placebo, 0.3 mg test compound, and 1.0 mg test compound.
- (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide can improve cognition at an unexpectedly low free plasma concentration, it is less likely to elicit harmful side-effects on its own and is less likely to exhibit harmful interactions with other drugs. Due to the unexpectedly low free plasma concentration required and the long half-life, (R)-7- chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is expected to have special drug properties. These properties include a high margin of safety and a favorable dosing regimen (e.g., once daily dosing), both of which are highly advantageous for treating patients with cognitive defects as well as patients that are required to take additional medications.
- Impairment of the ability of central nervous system to inhibit irrelevant sensory information has long been used as a model for understanding the deficits of attention seen in schizophrenic patients.
- Two approaches to the measurement of this ability have commonly been employed (see (Heinrichs, 2004; Potter et al., 2006; Turetsky et al., 2007; Umbricht and Krljes, 2005) for reviews and meta-analyses): (1) the sensory gating paradigm in which the presentation of one stimulus normally suppresses the response elicited by a stimulus which rapidly follows it. Schizophrenic patients typically exhibit less suppression (gating) of the second response. (2) the oddball or orienting paradigm in which a rare or unexpected event elicits a diminished response in schizophrenic patients because attentional resources are inappropriately focused on less salient aspects of the environment.
- Two responses are commonly used assess brain activity: (1) the auditory P50 response elicited by the second member of a pair of clicks; and (2) the mismatch negativity (MMN) or N2 response evoked by a rarely occurring pure tone of no instructed relevance to the patient.
- Abnormalities in both P50 gating and the MMN have been reported in schizophrenic patients. Described below are studies assessing both of these responses in patients treated with (R)-7- chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride salt ("the test compound”). Also presented below are studies assessing the influence of the test compound on the NlOO and P300 components of the evoked response. These components emerge after the P50 component and are as much related to attention to, and memory for, task relevant stimuli as to the neural processes by which task irrelevant stimuli are filtered (Turetsky et al., 2007; and Sandman and Patterson, 2000).
- the neurobiology of the MMN is more complex. Imaging studies suggest that the primary and secondary auditory cortices in the temporal lobe are important for its generation (Naatanen and Alho, 1995). The dorsolateral prefrontal cortex also contributes (Schall et al., 2003). The neurotransmitter systems underlying the MMN are understudied and largely unknown. Yet, as is the case for P50, nicotinic cholinergic systems appear important (Baldeweg et al., 2006; Dunbar et al., 2007).
- test described above were used to study the effect of the test compound on cognition in patients suffering from schizophrenia. Prior to testing the patient were dosed with: 1 mg of the test compound daily, 0.3 mg of the test compound daily or were administered a placebo for 20 days. Subjects were tested as described below.
- Electrodes were collected from 63 tin electrodes positioned by an electrode cap (Compumedics Neuroscan, Inc.). Additional electrodes of the same type were applied to the mid-forehead (ground) and in a vertical orientation above and below the left eye. Interelectrode impedances were maintained below 10 kOhms. All recordings were made with the subject sitting upright and relaxed but awake.
- the EEG and eye movement signals were sampled by an analog-to-converter programmed to retain EEG activity from 50 msec preceding to 325 msec following click onset.
- the sampling rate was 1000 Hz.
- the digitized signals were stored in a database for subsequent analysis.
- the 150 sweeps of Sl and S2 responses were screened and sweeps with voltage deviations greater than 100 microvolts in the eye movement channels were rejected. The remaining accepted sweeps were formed into time point averages. While blinded to group assignment, the investigator visually examined the evoked potential waveforms at the FCz electrode site. When possible, the investigator identified a negative trough immediately prior to the P50, the P50 itself, and the following NlOO component. Admittedly, a distinct P50 component could not be visually identified in all patients at all time points. In those cases, the data were coded as missing.
- P50 response amplitude was calculated as the voltage difference between the P50 peak and the preceding negative trough.
- the P50 gating ratio was then calculated after (Olincy et al., 2006) as the amplitude of the P50 response to the second (test) stimulus divided by the amplitude of the P50 response to the first (conditioning) stimulus. A small gating ratio is considered normal or optimal.
- the P50 amplitude difference (Fuerst et al., 2007) was also measured. It was the amplitude of the conditioning stimulus P50 response minus the amplitude of the test stimulus P50 response. A large P50 amplitude difference indicates normal gating.
- NlOO amplitude was calculated as the peak voltage of NlOO minus the average voltage during the brief, 50 msec prestimulus period. As was the case for P50, NlOO responses to the conditioning and test stimuli were calculated as ratios as well as differences.
- the MMN and P300 components were elicited during the so-called oddball sequence.
- the stimulus sequence was a series of lower (500 Hz) and higher (1000 Hz) pitched pure tones presented at a rate of 1 tone per 0.6 sec.
- the tones were 50 msec in duration, 50 dB above hearing level, and randomly interspersed.
- the higher pitched tone was the oddball event. Across the series of 600 tones, it occurred at a probability of 0.2.
- the other tone occurred at the complementary probability of 0.8. Patients were instructed to ignore the tones and instead attend to a magazine held in the lap.
- EEG and EOG activity were digitized at a rate of 500 Hz per channel for 50 msec preceding and 500 msec following stimulus onset. Trials contaminated by eyeb links or eye movements were removed.
- the MMN was measured by an automated algorithm that computed the summed amplitude, relative to the prestimulus baseline, over a 100- 200 msec time window following the onsets of the rare (oddball) and frequent tones. MMN was then recalculated as the voltage difference between these responses.
- P300 amplitude was measured at the Pz electrode site as the peak amplitude between 250 and 500 msec following stimulus onset.
- Figure 1 presents the results of simple analyses of co variance wherein all time points during the treatment period with valid data were averaged together to yield a single value. This value was then adjusted by regressing it against the baseline value and estimating a new value as if all patients possessed the same baseline. Then, a simple F test was performed. In support of the assumption of no significant differences between the treatment groups at the baseline (i.e., before treatment), we conducted simple ANOVAs evaluating the effect of treatment on all of the evoked potential components discussed presently. In no case did treatment significantly affect the baseline value.
- the right panel of Figure 1 shows the P50 amplitude difference score — a metric with superior reliability. It likewise shows normalization at the high dose.
- Figure 2 presents an identical analysis of the NlOO gating ratio and amplitude difference.
- In the left panel of Figure 2 normalization is suggested by a lower score.
- MMN was calculated as the voltage difference over 100-200 msec post-stimulus onset between the responses to the rare and frequent stimuli. A more negative MMN suggests normal cognitive function.
- P300 is not entirely independent of MMN.
- P300 was calculated as the peak amplitude relative to the average voltage of the waveform during the 50 msec prestimulus period. A more positive P300 response is indicative of improved cognitive function.
- P300 is maximal in amplitude when the eliciting stimulus is both rare and task relevant (i.e., attended). In the present study, the rare stimulus was not task relevant.
- P300 amplitude is very small in comparison to amplitudes recorded under active task conditions.
- the present P300 component is more similar to the small, frontally-generated P300a described by Knight and colleagues than the large, parietally- generated P300b described in most studies of attentional dysfunction in schizophrenia.
- the relative sensitivity or insensitivity of various evoked response components to the test compound may be related to their size and reliability of measurement.
- sensitivity differences may relate to differences across the components in their neural generators and innervation by cholinergic afferents.
- the two components (MMN and P300) which were most sensitive to the test compound are generated or modulated by frontal cortical pathways that receive input from brainstem cholinergic fibers.
- the P50 is, in contrast, generated subcortically.
- test compound The impact of the test compound on cognition in normal subjects was assessed as described below. In these studies subjects were treated with the test compound dissolved in cranberry juice.
- test compound The impact of the test compound on cognition in normal subjects was assessed in a SAD (Single Ascending Dose) study with the Digit Symbol Substitution Test (DSST). Utilizing this test, the test compound was shown to have pro-cognitive effects at daily a dose as low as 1 mg. This is unexpected since acetylcholine esterase inhibitors, which indirectly activates the alpha 7 receptor by increasing acetylcholine levels, are not understood to exhibit pro-cognitive effects in normal subject and even in patients with cognitive impairment are not understood to exhibit pro- cognitive effects after a single dose. The positive effects of the test compound in the DSST indicate a beneficial effect on working memory and executive function.
- the test compound was shown to have pro-cognitive effects at daily a dose as low as 1 mg.
- the CogState battery is a proprietary computerized cognitive battery of tests measure various cognitive domains including: attention, identification capability, working memory, visual memory, and executive function.
- the test compound was found to have a positive impact on: visual motor skills, learning, executive function, and delayed memory.
- the profile of the response was unique insofar as the test compound had positive effects on non-verbal learning and memory and executive function without having a stimulatory effect on attention.
- a small molecule drug In order for a small molecule to exert action at its target, often a cell receptor, it must bind to its target.
- a small molecule drug is expected to exhibit activity when the free drug concentration at the target (i.e., the concentration of drug that is free and available to bind to the target) approaches or exceeds the K 1 of the drug for target.
- the free drug concentration at the target i.e., the concentration of drug that is free and available to bind to the target
- the free drug concentration in a particular tissue is about equal to the free drug concentration in plasma (Mauer et al 2005 and Tf ainor 2007).
- the free plasma concentration is generally considered to represent the maximum possible free drug concentration.
- the total plasma drug concentration and the fraction that binds to plasma protein can both be measured using techniques known to those of skill in the art.
- the maximum plasma concentration was determined and used to calculate the maximum free drug concentration which was used to determine the maximum free drug concentration as a fraction of the ECref of the drug for human alpha7 receptor and the maximum free drug concentration as a fraction of the K 1 of the drug for rat brain alpha7 receptors.
- the EC re f the concentration of drug which elicits equal response in oocytes trans fected with cloned human alpha7 receptor at 50 ⁇ M acetylcholine (the endogenous receptor ligand), was determined to be 0.158 ⁇ M.
- the K 1 for rat brain alpha7 receptors was determined to be 10 nM.
- Table 2 presents half-life (Iy 2 ) data for (R)-7-chloro-N-(quinuclidin-3- yl)benzo[b]thiophene-2-carboxamide obtained from pre-clinical species as well as the half-life in humans determined in clinical trials.
- the half-life determined in rat and dog suggested a human half-life much shorter than the observed 60 hr half-life (initial allometric scaling suggested a half-life of about 8 hours).
- the unexpectedly long half-life in humans has several advantages. It allows for once a day dosing.
- the drug will also have a very small dynamic plasma range over the course of a day (about 15- 20%). Thus, if a patient misses a daily dose, the plasma level and the consequent brain level will not be altered by a great degree. This means that the beneficial effects of the drug will be less dependent upon careful adherence to a specific dosing scheme.
- long half-life and slow elimination also mean that the final dose will be lower than expected.
- Schizophrenia sensory gating, and nicotinic receptors. Schizophr Bull 24, 189-202.
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Priority Applications (35)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK09756921.4T DK2355822T3 (da) | 2008-11-19 | 2009-11-19 | behandling af kognitive forstyrrelser med (R)-7-chlor-N-(quinuclidin-3-yl)benzoe[b]thiophen-2-carboxamid og farmaceutisk acceptable salte deraf |
CA2744278A CA2744278C (en) | 2008-11-19 | 2009-11-19 | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
SI200930466T SI2355822T1 (sl) | 2008-11-19 | 2009-11-19 | Zdravljenje kognitivnih motenj z (R)-7-kloro-N-(kinuklidin-3-il)benzo(b)tiofen-2-karboksamidom in njegovimi farmacevtsko sprejemljivimi solmi |
CN2009801546937A CN102281878A (zh) | 2008-11-19 | 2009-11-19 | 用(R)-7-氯-N-(奎宁环-3-基)苯并[b]噻吩-2-甲酰胺及其可药用盐治疗认知障碍 |
JP2011537621A JP5272080B2 (ja) | 2008-11-19 | 2009-11-19 | (R)−7−クロロ−N−(キヌクリジン−3−イル)ベンゾ[b]チオフェン−2−カルボキサミド及びその製薬上許容しうる塩を用いた認知障害の治療 |
RS20120560A RS52583B (en) | 2008-11-19 | 2009-11-19 | TREATMENT OF COGNITIVE DISORDERS WITH (R) -7-CHLORO-N- (HINUCLIDIN-3-IL) BENZO [B] THIOPHENE-2-CARBOXAMIDE OR ITS PHARMACEUTICALLY ACCEPTABLE SALTS |
NZ593467A NZ593467A (en) | 2008-11-19 | 2009-11-19 | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
EP18152484.4A EP3357495B1 (en) | 2008-11-19 | 2009-11-19 | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
US13/129,782 US8642638B2 (en) | 2008-11-19 | 2009-11-19 | Treatment of cognitive disorders with (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
KR1020187002503A KR20180011888A (ko) | 2008-11-19 | 2009-11-19 | (r)-7-클로로-n-(퀴누클리딘-3-일)벤조[b]티오펜-2-카르복사미드 및 그 약학적으로 허용가능한 염을 이용한 인지 장애의 치료 |
PL09756921T PL2355822T3 (pl) | 2008-11-19 | 2009-11-19 | Leczenie zaburzeń funkcji poznawczych (R)-7-chloro-N-(chinuklidyn-3-ylo)benzo[b]tiofeno-2-karboksyamidem i jego farmaceutycznie dopuszczalnymi solami |
MX2011005270A MX2011005270A (es) | 2008-11-19 | 2009-11-19 | Tratamiento de trastornos cognitivos con (r)-7-cloro-n-(quinuclidi n-3-il)benzo[b]tiofeno-2-carboxamida y sales farmaceuticamente aceptables de la misma. |
KR1020147032489A KR20140146216A (ko) | 2008-11-19 | 2009-11-19 | (r)-7-클로로-n-(퀴누클리딘-3-일)벤조[b]티오펜-2-카르복사미드 및 그 약학적으로 허용가능한 염을 이용한 인지 장애의 치료 |
ES09756921T ES2396300T3 (es) | 2008-11-19 | 2009-11-19 | Tratamiento de trastornos cognitivos con (R)-7-cloro-N-(quinuclidin-3-il)benzo[b]tiofeno-2-carboxamida y sales farmacéuticamente aceptables de la misma |
RU2011124515/15A RU2532327C2 (ru) | 2008-11-19 | 2009-11-19 | ЛЕЧЕНИЕ КОГНИТИВНЫХ РАССТРОЙСТВ (R)-7-ХЛОР-N-(ХИНУКЛИДИН-3-ИЛ) БЕНЗО[b] ТИОФЕН-2-КАРБОКСАМИДОМ И ЕГО ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫМИ СОЛЯМИ |
BRPI0922057A BRPI0922057A2 (pt) | 2008-11-19 | 2009-11-19 | tratamento dos transtorno cognitivos com (r)-7-cloro-n-(quiniclidin-3-il)benzo[b]tiofeno-2-carboxamida e sais farmeceuticamente aceitaveis do mesmo |
EP09756921A EP2355822B1 (en) | 2008-11-19 | 2009-11-19 | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
AU2009316557A AU2009316557B2 (en) | 2008-11-19 | 2009-11-19 | Treatment of cognitive disorders with (R)-7-chloro-N-(quinuclidin-3-yl) benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
IL212921A IL212921A (en) | 2008-11-19 | 2011-05-16 | (r) –7 – chloro n –– (quinoclidin – 3 – ram) benzo [b] thiophene-2-carboxamide for the preparation of drugs for the treatment of cognitive disorders |
EC2011011076A ECSP11011076A (es) | 2008-11-19 | 2011-05-23 | Tratamiento de trastornos cognitivos con (r)-7-cloro-n-(quinuclidin-3-il)benzo[b]tiofeno-2-carboxamida y sales farmacéuticamente aceptables de la misma |
ZA2011/04044A ZA201104044B (en) | 2008-11-19 | 2011-05-31 | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
HK11113010.6A HK1158520A1 (en) | 2008-11-19 | 2011-11-30 | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3- yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
US13/674,290 US8569354B2 (en) | 2008-11-19 | 2012-11-12 | Treatment of cognitive disorders with (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
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US14/139,178 US20140148479A1 (en) | 2008-11-19 | 2013-12-23 | Treatment of Cognitive Disorders with (R)-7-Chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-Carboxamide and Pharmaceutically Acceptable Salts Thereof |
US14/175,654 US8815933B2 (en) | 2008-11-19 | 2014-02-07 | Treatment of cognitive disorders with (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
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US14/509,305 US20150265583A1 (en) | 2008-11-19 | 2014-10-08 | Treatment of Cognitive Disorders with (R)-7-Chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-Carboxamide and Pharmaceutically Acceptable Salts Thereof |
IL242034A IL242034A (en) | 2008-11-19 | 2015-10-12 | Use of (r) -7- chlorone- (quinoclidin-3-yl) benzo [b] thiophene-2-carboxamide for the preparation of drugs for the treatment of cognitive disorders |
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US15/796,475 US20180271844A1 (en) | 2008-11-19 | 2017-10-27 | Treatment of Cognitive Disorders with (R)-7-Chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-Carboxamide and Pharmaceutically Acceptable Salts Thereof |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2640378A1 (en) * | 2010-11-18 | 2013-09-25 | Envivo Pharmaceuticals, Inc. | Treatment of inflammation with certain alpha-7 nicotinic acid receptor agonists in combination with acetylcholinesterase inhibitors |
EP2706854A1 (en) * | 2011-05-09 | 2014-03-19 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with certain alpha-7 nicotinic acid receptor agonists in combination with nicotine |
EP2725906A1 (en) * | 2011-07-01 | 2014-05-07 | Envivo Pharmaceuticals, Inc. | Methods of treatment of limited cognitive impairment |
US8884017B2 (en) | 2001-12-27 | 2014-11-11 | Bayer Intellectual Property Gmbh | 2-heteroarylcarboxylic acid amides |
US20150126547A1 (en) * | 2012-05-08 | 2015-05-07 | Forum Pharmaceuticals, Inc. | Methods of Maintaining, Treating or Improving Cognitive Function |
US9108961B2 (en) | 2010-05-17 | 2015-08-18 | Forum Pharmaceuticals, Inc. | Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3017886A1 (en) | 2008-11-19 | 2010-05-27 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
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WO2020056418A1 (en) | 2018-09-14 | 2020-03-19 | Neuroenhancement Lab, LLC | System and method of improving sleep |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003055878A1 (de) * | 2001-12-27 | 2003-07-10 | Bayer Healthcare Ag | 2-heteroarylcarbonsäureamide |
Family Cites Families (112)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5122528A (en) | 1983-12-22 | 1992-06-16 | Erbamont, Inc. | Analgesic use of benzobicyclic carboxamides |
US4605652A (en) | 1985-02-04 | 1986-08-12 | A. H. Robins Company, Inc. | Method of enhancing memory or correcting memory deficiency with arylamido (and arylthioamido)-azabicycloalkanes |
EP0201165B1 (en) | 1985-03-14 | 1994-07-20 | Beecham Group Plc | Medicaments for the treatment of emesis |
HU895334D0 (en) | 1986-07-30 | 1990-01-28 | Sandoz Ag | Process for the preparation of nasal pharmaceutical compositions |
DE3827253A1 (de) | 1987-08-20 | 1989-03-02 | Sandoz Ag | Ester und amide von cyclischen carbonsaeuren und cyclischen alkoholen und aminen sowie verfahren zu deren herstellung und sie enthaltende therapeutische zusammensetzungen |
DE3740984A1 (de) | 1987-12-03 | 1989-06-15 | Sandoz Ag | N-oxide von heterocyclischen carbonsaeurederivaten bzw. verfahren zu deren herstellung und deren verwendung |
US5198437A (en) | 1987-12-10 | 1993-03-30 | Duphar International Research B.V. | 1,7-annelated indolecarboxylic acid esters and amides |
IL88615A (en) | 1987-12-10 | 1992-11-15 | Duphar Int Res | 1,7-annelated indolecarboxylic acid esters and carboxamides,their preparation and pharmaceutical compositions containing them |
US4863919A (en) | 1988-02-01 | 1989-09-05 | A. H. Robins Company, Incorporated | Method of enhancing memory or correcting memory deficiency with arylamido(and arylthiomido)-azabicycloalkanes |
DE3810552A1 (de) | 1988-03-29 | 1989-10-19 | Sandoz Ag | Ester und amide von indol-, benzo(b)thiopen-, benzo(b)furancarbonsaeuren oder 4-amino-2-methoxy-benzolsaeuren mit n-heterocyclischen oder n-heterobicyclischen alkoholen oder aminen, verfahren zu deren herstellung sie enthaltende pharmazeutische zusammensetzungen sowie applikator zur verabreichung derselben |
EP0353371A1 (en) | 1988-08-04 | 1990-02-07 | Synthelabo | Memory enhancing-R-N-(1-azabicyclo[2.2.2] oct-3-yl) benzamides and thiobenzamides |
IE62662B1 (en) | 1989-01-06 | 1995-02-22 | Elan Corp Plc | Use of nicotine in the treatment of conditions susceptible to said treatment |
US5189041A (en) | 1990-11-16 | 1993-02-23 | Syntex (U.S.A.) Inc. | Tricyclic 5-ht3 receptor antagonists |
US5114947A (en) | 1990-12-27 | 1992-05-19 | Erbamont Inc. | Method for alleviating anxiety using benzobicyclic carboxamides |
DE4115215A1 (de) | 1991-05-10 | 1992-11-12 | Merck Patent Gmbh | Indolderivate |
SE9201478D0 (sv) | 1992-05-11 | 1992-05-11 | Kabi Pharmacia Ab | Heteroaromatic quinuclidinenes, their use and preparation |
US5977144A (en) | 1992-08-31 | 1999-11-02 | University Of Florida | Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines |
EE03399B1 (et) | 1994-08-24 | 2001-04-16 | Astra Aktiebolag | Teraapias kasutatavad spiro-asabitsüklilised ühendid ja nende valmistamise protsess |
US5656638A (en) | 1995-04-18 | 1997-08-12 | Geron Corporation | Telomerase inhibitors |
US5703116A (en) | 1995-04-18 | 1997-12-30 | Geron Corporation | Telomerase Inhibitors |
US5863936A (en) | 1995-04-18 | 1999-01-26 | Geron Corporation | Telomerase inhibitors |
US5760062A (en) | 1995-04-18 | 1998-06-02 | Geron Corporation | Telomerase inhibitors |
GB9606736D0 (en) | 1996-02-19 | 1996-06-05 | Shire International Licensing | Therapeutic method |
FR2756826B1 (fr) | 1996-12-05 | 1999-01-08 | Adir | Nouveaux derives tetrahydropyridiniques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
CZ298824B6 (cs) | 1997-05-30 | 2008-02-20 | Neurosearch A/S | Deriváty 8-azabicyklo[3.2.1]okt-2-enu, zpusob jejich prípravy a jejich použití |
US7214686B2 (en) | 1997-06-30 | 2007-05-08 | Targacept, Inc. | Pharmaceutical compositions and methods for effecting dopamine release |
JPH1180027A (ja) | 1997-09-12 | 1999-03-23 | Dai Ichi Seiyaku Co Ltd | 向知性薬 |
US6875606B1 (en) | 1997-10-23 | 2005-04-05 | The United States Of America As Represented By The Department Of Veterans Affairs | Human α-7 nicotinic receptor promoter |
US6277870B1 (en) | 1998-05-04 | 2001-08-21 | Astra Ab | Use |
WO2000017356A2 (en) | 1998-09-18 | 2000-03-30 | The Rockefeller University | Lynx, a novel family of receptor ligands in the central nervous system, corresponding nucleic acids and proteins and uses therof |
US6432975B1 (en) | 1998-12-11 | 2002-08-13 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
US6953855B2 (en) | 1998-12-11 | 2005-10-11 | Targacept, Inc. | 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof |
SE9900100D0 (sv) | 1999-01-15 | 1999-01-15 | Astra Ab | New compounds |
FR2790474B1 (fr) | 1999-03-05 | 2001-04-06 | Synthelabo | Derives de pyridopyranoazepines, leur preparation et leur application en therapeutique |
FR2791678B1 (fr) | 1999-03-30 | 2001-05-04 | Synthelabo | Derives de 1,4-diazabicyclo [3.2.2] nonane-4-carboxylates et -carboxamides, leur preparation et leur application en therapeutique |
US6416735B1 (en) | 1999-11-08 | 2002-07-09 | Research Triangle Institute | Ligands for α-7 nicotinic acetylcholine receptors based on methyllcaconitine |
JP2003530542A (ja) | 1999-12-01 | 2003-10-14 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | 神経変性疾患の診断方法 |
WO2001044283A2 (en) | 1999-12-14 | 2001-06-21 | Pharmacia & Upjohn Company | Human ion channels |
FR2804430B1 (fr) | 2000-01-28 | 2002-03-22 | Sanofi Synthelabo | Derives de 4-heteroaryl-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
GB0010955D0 (en) | 2000-05-05 | 2000-06-28 | Novartis Ag | Organic compounds |
EP1287001B1 (en) | 2000-06-06 | 2004-09-29 | Pfizer Products Inc. | Thiophene derivatives useful as anticancer agents |
TW593223B (en) | 2000-06-20 | 2004-06-21 | Merz Pharma Gmbh & Co Kgaa | 1-amino-alkylcyclohexanes as 5-HT3 and neuronal nicotinic receptor antagonists |
FR2810664B1 (fr) | 2000-06-27 | 2004-12-24 | Adir | Nouveaux composes cyclopropaniques 1,1 et 1,2-dissubstitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
JP4616971B2 (ja) | 2000-07-18 | 2011-01-19 | 田辺三菱製薬株式会社 | 1−アザビシクロアルカン化合物およびその医薬用途 |
US20030092613A1 (en) | 2000-08-14 | 2003-05-15 | Lee Daniel H. S. | Alpha7 nicotinic receptor peptides as ligands for beta amyloid peptides |
US6492385B2 (en) | 2000-08-18 | 2002-12-10 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
JP2004506735A (ja) | 2000-08-18 | 2004-03-04 | ファルマシア・アンド・アップジョン・カンパニー | 疾患治療用キヌクリジン置換アリール化合物 |
WO2002016356A2 (en) | 2000-08-18 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl moieties for treatment of disease (nicotinic acetylcholine receptor ligands) |
US6500840B2 (en) | 2000-08-21 | 2002-12-31 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
DE10044905A1 (de) | 2000-09-12 | 2002-03-21 | Merck Patent Gmbh | (2-Azabicyclo[2.2.1]hept-7-yl)methanol-Derivate als nikontinische Acetylcholinrezeptor Agonisten |
US20020086871A1 (en) | 2000-12-29 | 2002-07-04 | O'neill Brian Thomas | Pharmaceutical composition for the treatment of CNS and other disorders |
EP1231212B1 (en) | 2001-02-06 | 2006-12-20 | Pfizer Products Inc. | Pharmaceutical compositions for the treatment of disorders of the CNS and other disorders |
GB0108337D0 (en) | 2001-04-03 | 2001-05-23 | Novartis Ag | Organic compounds |
US6569865B2 (en) | 2001-06-01 | 2003-05-27 | Astrazeneca Ab | Spiro 1-azabicyclo[2.2.2]octane-3,2′(3′h)-furo[2,3-b]pyridine |
AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
CA2455773A1 (en) | 2001-08-24 | 2003-03-06 | Pharmacia & Upjohn Company | Substituted-aryl 7-aza¬2.2.1|bicycloheptanes for the treatment of disease |
JP2003081978A (ja) | 2001-09-10 | 2003-03-19 | Mitsubishi Pharma Corp | スピロ環式化合物およびその医薬用途 |
BR0212477A (pt) | 2001-09-12 | 2004-08-24 | Upjohn Co | 7-aza[2.2.1] bicicloheptanos substituìdos para o tratamento de doenças |
US6911543B2 (en) | 2001-10-02 | 2005-06-28 | Pfizer Inc. | Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease |
CA2464194A1 (en) | 2001-10-26 | 2003-05-08 | Pharmacia & Upjohn Company | N-azabicyclo-substituted hetero-bicyclic carboxamides as nachr agonists |
MXPA04004464A (es) | 2001-11-08 | 2004-08-11 | Upjohn Co | Compuestos de heteroarilo sustituido con azabiciclo para el tratamiento de enfermedades. |
JP2005510523A (ja) | 2001-11-09 | 2005-04-21 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | アザ二環式フェニル縮合複素環式化合物、及びα7NACHRリガンドとしての当該化合物の使用 |
GB0127008D0 (en) | 2001-11-09 | 2002-01-02 | Novartis Ag | Organic compounds |
DE10156719A1 (de) | 2001-11-19 | 2003-05-28 | Bayer Ag | Heteroarylcarbonsäureamide |
FR2832714B1 (fr) | 2001-11-23 | 2004-07-16 | Sanofi Synthelabo | Derives de 4-(oxazolopyridin-2-yl)-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
FR2832712B1 (fr) | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(oxadiazol-3-yl)-1,4-diazabicyclo[3.2.2]nonane, leur preparation et leur application en therapeutique |
FR2832713B1 (fr) | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(1,3,4-thiadiazol-2-yl)-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
CN100371714C (zh) | 2001-12-14 | 2008-02-27 | 塔加西普特公司 | 治疗中枢神经系统病症的方法和组合物 |
DE10162375A1 (de) | 2001-12-19 | 2003-07-10 | Bayer Ag | Bicyclische N-Aryl-amide |
DE10162442A1 (de) | 2001-12-19 | 2003-07-03 | Bayer Ag | Monocyclische N-Aryl-amide |
MXPA04007936A (es) | 2002-02-15 | 2004-11-26 | Upjohn Co | Compuestos de aril-sustituidos para el tratamiento de enfermedades. |
BR0307735A (pt) | 2002-02-19 | 2005-01-25 | Upjohn Co | Carboxamidas heteroaromáticas com ligação-n em ponte biciclìcas fundidas para o tratamento de doença |
JP2005523287A (ja) | 2002-02-19 | 2005-08-04 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 疾患治療用アザビシクロ化合物 |
CA2475773A1 (en) | 2002-02-20 | 2003-09-04 | Pharmacia & Upjohn Company | Azabicyclic compounds with alfa7 nicotinic acetylcholine receptor activity |
DE10211415A1 (de) | 2002-03-15 | 2003-09-25 | Bayer Ag | Bicyclische N-Biarylamide |
DE10211416A1 (de) | 2002-03-15 | 2003-09-25 | Bayer Ag | Essig- und Propionsäureamide |
US20030236287A1 (en) | 2002-05-03 | 2003-12-25 | Piotrowski David W. | Positive allosteric modulators of the nicotinic acetylcholine receptor |
EP1502110A4 (en) | 2002-05-09 | 2007-09-05 | Memory Pharm Corp | QM-7 AND QT-6 CELLS TRANSFECTED WITH MUTANT CHANNEL RECEPTORS WITH SURFACE EXPRESSION AND TESTS USING THESE TRANSFECTED CELLS |
CA2495432A1 (en) | 2002-07-17 | 2004-01-22 | Warner-Lambert Company Llc | Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib |
DE10234424A1 (de) | 2002-07-29 | 2004-02-12 | Bayer Ag | Benzothiophen-, Benzofuran- und Indolharnstoffe |
AU2003249532A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | 4-hydroxyquinoline derivatives as matrix metalloproteinase inhibitors |
WO2004014909A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Fused tetrahydropyridine derivatives as matrix metalloproteinase inhibitors |
GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
ES2405594T3 (es) | 2002-09-25 | 2013-05-31 | Memory Pharmaceuticals Corporation | Idazoles, benzotiazoles y benzisotiazoles, y preparación y usos de los mismos |
MXPA05005666A (es) | 2002-12-11 | 2005-07-26 | Pharmacia & Upjohn Co Llc | Tratamiento de enfermedades con combinaciones de agonistas del receptor nicotinico de acetilcolina alfa-7 y otros compuestos. |
US20050031651A1 (en) | 2002-12-24 | 2005-02-10 | Francine Gervais | Therapeutic formulations for the treatment of beta-amyloid related diseases |
CA2519265A1 (en) | 2003-03-28 | 2004-10-07 | Pharmacia & Upjohn Company Llc | Positive allosteric modulators of the nicotinic acetylcholine receptor |
US20050119249A1 (en) | 2003-12-02 | 2005-06-02 | Erik Buntinx | Method of treating neurodegenerative diseases using D4 and 5-HT2A antagonists, inverse agonists or partial agonists |
US20050245531A1 (en) | 2003-12-22 | 2005-11-03 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
BRPI0508771A (pt) | 2004-03-25 | 2007-08-14 | Memory Pharm Corp | indazóis, benzotiazóis, benzoisotiazóis, benzisoxazóis, e a preparação e usos dos mesmos |
AU2004325725A1 (en) | 2004-12-10 | 2006-06-22 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
AU2006295397A1 (en) | 2005-09-23 | 2007-04-05 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
CL2007003049A1 (es) | 2006-10-23 | 2008-05-16 | Cephalon Inc Pharmacopeia Drug | Compuestos derivados de 2,4-diaminopirimidina; composicion farmaceutica, utiles para tratar trastornos proliferativos. |
BRPI0811280B8 (pt) | 2007-05-11 | 2021-05-25 | Pfizer | compostos amino-heterocíclicos, composição farmacêutica que os compreende e usos dos referidos compostos |
AR068121A1 (es) | 2007-08-31 | 2009-11-04 | Eisai R&D Man Co Ltd | Compuestos multiciclicos para tratar enfermedades neurodegenerativas |
US7935815B2 (en) | 2007-08-31 | 2011-05-03 | Eisai R&D Management Co., Ltd. | Imidazoyl pyridine compounds and salts thereof |
WO2009046025A1 (en) | 2007-10-01 | 2009-04-09 | Comentis, Inc. | Quinuclidin-4-ylmethyl 1h-indole-3-carboxylate derivatives as alpha 7 nicotinic acetylcholine receptor ligands for the treatment of alzheimer's disease |
SG186018A1 (en) | 2007-11-21 | 2012-12-28 | Abbott Lab | Biaryl substituted azabicyclic alkane derivatives as nicotinic acetylcholine receptor activity modulators |
DK2282779T3 (da) | 2008-04-29 | 2013-05-27 | Pharnext | Nye terapeutiske fremgangsmåder til behandling af alzheimer sygdom og beslægtede lidelser gennem en modulation af cellestress-respons |
WO2009133141A2 (en) | 2008-04-29 | 2009-11-05 | Pharnext | New therapeutic approaches for treating alzheimer disease and related disorders through a modulation of angiogenesis |
CA2722295C (en) | 2008-04-29 | 2019-01-15 | Pharnext | Combination compositions for treating alzheimer disease and related disorders with zonisamide and acamprosate |
MX2011005096A (es) | 2008-11-13 | 2011-11-18 | Link Medicine Corp | Derivados de azaquinolinona y usos de los mismos. |
CA3017886A1 (en) | 2008-11-19 | 2010-05-27 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
US8674095B2 (en) | 2008-12-19 | 2014-03-18 | Afraxis Holdings, Inc. | Compounds for treating neuropsychiatric conditions |
JP2012514011A (ja) | 2008-12-30 | 2012-06-21 | ラモト アト テルーアビブ ユニバーシティー リミテッド | Napを用いる併用治療の方法 |
TWI404721B (zh) | 2009-01-26 | 2013-08-11 | Pfizer | 胺基-雜環化合物 |
WO2010095940A2 (en) | 2009-02-20 | 2010-08-26 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
KR20110122746A (ko) | 2009-02-26 | 2011-11-10 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 질소를 함유하는 융합된 헤테로사이클릭 화합물 및 β 아밀로이드 생산 저해제로서의 용도 |
MX2011010782A (es) | 2009-04-13 | 2012-01-20 | Theravance Inc | Compuestos agonistas del receptor 5-ht4 para el tratamiento de trastornos cognitivos. |
BRPI1010024A2 (pt) | 2009-06-05 | 2019-09-24 | Link Medicine Corp | derivados de aminopirrolidinona e uso dos mesmos |
WO2011057199A1 (en) | 2009-11-06 | 2011-05-12 | Adenios, Inc. | Compositions for treating cns disorders |
US20110274628A1 (en) | 2010-05-07 | 2011-11-10 | Borschke August J | Nicotine-containing pharmaceutical compositions |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003055878A1 (de) * | 2001-12-27 | 2003-07-10 | Bayer Healthcare Ag | 2-heteroarylcarbonsäureamide |
Non-Patent Citations (3)
Title |
---|
ACKER BRAD A ET AL: "Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridi ne-5-carboxamide as an agonist of the alpha 7 nicotinic acetylcholine receptor: In vitro and in vivo activity", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 18, no. 12, June 2008 (2008-06-01), pages 3611 - 3615, XP002572658, ISSN: 0960-894X * |
GRAY J A ET AL: "The pipeline and future of drug development in schizophrenia.", MOLECULAR PSYCHIATRY OCT 2007, vol. 12, no. 10, October 2007 (2007-10-01), pages 904 - 922, XP002572660, ISSN: 1359-4184 * |
WISHKA DONN G ET AL: "Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine- 5-carboxamide, an agonist of the alpha 7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: Synthesis and structure-activity relationship", JOURNAL OF MEDICINAL CHEMISTRY, vol. 49, no. 14, July 2006 (2006-07-01), pages 4425 - 4436, XP002572659, ISSN: 0022-2623 * |
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Publication number | Priority date | Publication date | Assignee | Title |
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US9108961B2 (en) | 2010-05-17 | 2015-08-18 | Forum Pharmaceuticals, Inc. | Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride |
US9550767B2 (en) | 2010-05-17 | 2017-01-24 | Forum Pharmaceuticals, Inc. | Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate |
US9273044B2 (en) | 2010-05-17 | 2016-03-01 | Forum Pharmaceuticals, Inc. | Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate |
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