- Copper-mediated etherification of arenes with alkoxysilanes directed by an (2-aminophenyl)pyrazole group
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An efficient copper-mediated etherification of inert C-H bonds of (hetero)arenes with reagent-amounts of alkoxysilanes and alkanols has been developed using (2-aminophenyl)pyrazole (2-APP) as a removable directing group. The reaction is scalable, rapidly proceeds under an open atmosphere, and tolerates diverse functional groups to provide alkyl aryl ethers in high yields (up to 87%). As an application, the formal synthesis of anti-emetic drug metoclopramide is accomplished.
- Selvakumar, Jayaraman,Grandhi, Gowri Sankar,Sahoo, Harekrishna,Baidya, Mahiuddin
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Read Online
- BICYCLIC HETEROARYL DERIVATIVES AS ECTONUCLEOTIDE PYROPHOSPHATASE PHOSPHODIESTERASE 1 INHIBITORS
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The present disclosure provides certain bicyclic heteroaryl compounds that inhibit ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzymatic activity and are therefore useful for the treatment of diseases and conditions modulated at least in part by ENPP1. In some embodiments, the bicyclic heteroaryl compounds includes those of Formula (I). Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Paragraph 0325
(2020/10/21)
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- Novel multitarget-directed ligands targeting acetylcholinesterase and σ1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase
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Pleiotropic intervention may be a requirement for effective limitation of the progression of multifactorial diseases such as Alzheimer's Disease. One approach to such intervention is to design a single chemical entity capable of acting on two or more targets of interest, which are accordingly known as Multi-Target Directed Ligands (MTDLs). We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT4 receptor, which displays promising activities in vivo. Pharmacomodulation of donecopride allowed us to develop a novel series of indole derivatives possessing interesting in vitro activities toward AChE and the σ1 receptor. The crystal structures of complexes of the most promising compounds with Torpedo californica AChE were solved in order to further understand their mode of inhibition.
- Lalut, Julien,Santoni, Gianluca,Karila, Delphine,Lecoutey, Cédric,Davis, Audrey,Nachon, Florian,Silman, Israel,Sussman, Joel,Weik, Martin,Maurice, Tangui,Dallemagne, Patrick,Rochais, Christophe
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supporting information
p. 234 - 248
(2018/11/24)
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- As neuroprotective agents of pharmaceutical compounds
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The invention discloses a medicinal compound as a neuroprotective agent. The medicinal compound is a neuronal nitric oxide synthase-postsynaptic density protein 95 (nNOS-PSD95) decoupling agent. The medicinal compound is a benzene ring derivative shown in the general formula (I) or its pharmaceutically acceptable salt. The invention further discloses a preparation method of the medicinal compound and a use of the medicinal compound in prevention and treatment on neuronal damage influence-caused diseases.
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Paragraph 0694; 0695; 0696; 0697
(2019/06/26)
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- Synthetic method of 4-amino-5-chloro-2-methoxyl benzoic acid
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The invention discloses a synthetic method of 4-amino-5-chloro-2-methoxyl benzoic acid, wherein the synthetic method includes the steps of dimethyl sulphate methylation, N-chloro-succinimide chlorination, alkaline hydrolysis de-esterification and hydrochloric acid acidification to prepare an intermediate product, wherein aminosalicylic acid, which is low in cost and easy to obtain, is employed as a raw material. The synthetic method is reasonable and simple in process route design, is mild in reaction conditions, is easy to industrially operate, is low in costs of raw material and devices, is high in yield and product quality, and is effectively reduced in production cost.
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Paragraph 0025
(2016/10/27)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 59
(2012/11/08)
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- MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
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The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating diseases using such CFTR modulators.
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Page/Page column 66
(2010/07/08)
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- Compounds having beta adrenergic receptor agonist and muscarinic receptor antagonist activity
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This invention provides compounds of formula I: wherein R1, R2, R4, R5, R6, R7, R8a, R8b, W, a, b, c and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Accordingly, such compounds are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
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Page/Page column 30-31
(2008/06/13)
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- Crystalline form of a biphenyl compound
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The invention provides a crystalline 1,2-ethanedisulfonic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also provides pharmaceutical compositions comprising such a salt or prepared using such a salt; processes and intermediates for preparing such a salt; and methods of using such a salt to treat a pulmonary disorder.
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Page/Page column 12
(2008/06/13)
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- COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY
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This invention provides compounds of formula I wherein R1, R2, R3, R4, R5, R6, R7, R8a, R8b, W, a and b are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Accordingly, such compounds are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
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Page/Page column 76
(2008/06/13)
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- THERAPEUTIC AGENT FOR RESPIRATORY DISEASE CONTAINING 4-HYDROXYPIPERIDINE DERIVATIVE AS ACTIVE INGREDIENT
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An agent for preventing/treating respiratory diseases contains, as an active ingredient, a compound represented by following Formula (I): wherein A is a group represented by L-W [wherein L is a bond or CH2; and W is O, SOn (wherein n is 0 to 2), or -NR7-(wherein R7 is hydrogen or lower alkyl)]; each of G1 and G2 is (CH2)r (wherein r is 0 to 2), provided that when n is 1, G1 and G2 may be bridged by lower alkylene; Y is a lower alkylene or (substituted) benzylidene; Z is a bond or O, provided that when Z is a bond, Y may form a 5- or 6-membered ring with carbon on the benzene ring; R1 is, for example, NO2, a lower alkoxycarbonyl, (substituted) carbamoyl, (protected) hydroxyl group, (protected) carboxyl, or (protected) N-hydroxycarbamoyl; each of R2and R3 is hydrogen, halogen, (halogenated) lower alkyl, (halogenated) lower alkoxy or NO2; each of R4 and R5 is, for example, hydrogen, halogen, (halogenated) lower alkyl, (halogenated) lower alkoxy, CN, or lower alkylsulfonyl; and R6 is hydrogen or lower alkyl, a salt thereof or a solvate of them. It has excellent antitussive activity when used as an agent for preventing/treating respiratory diseases such as lung cancer, common cold syndrome, pulmonary tuberculosis, pneumonia, acute bronchitis or chronic bronchitis.
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Page/Page column 32
(2008/06/13)
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- FUSED HETEROCYCLIC COMPOUND HAVING ANTI-HCV EFFECT
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Disclosed is a compound represented by the formula (I) below, a pharmaceutically acceptable salt thereof, or a solvate of them. (I) (In the formula, A represents N or CH; Het represents any one of the following groups: (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k) wherein R0 and R respectively represent a hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted aryl or the like; R1 and R2 respectively represent a hydrogen, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl or the like; p is an integer of 0-3; and R3 represents an optionally substituted alkyl or the like.)
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Page/Page column 229-230
(2010/02/15)
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- Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
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The invention is directed to compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7a, R7b, W, G1, G2, a, b, c, d and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
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Page/Page column 46
(2008/06/13)
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- Biphenyl derivatives
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This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
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Page/Page column 51
(2008/06/13)
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- DIARYLMETHYL AND RELATED COMPOUNDS
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This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7, Ar1, Ar2, E, a, b, c, and z are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
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- Novel cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
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The present invention provides tricyclic carboxamide compounds and methods and pharmaceutical compositions for their use in treatment, prevention, or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including prevention and/or suppression of preterm labor, suppression of labor at term prior to caesarean deliver, and for the treatment of dysmenorrhea. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.
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- Novel pyrido cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
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The present invention provides novel tricyclic pyridyl carboxamides as well as methods and pharmaceutical compositions utilizing them compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including prevention and/or suppression of preterm labor, suppression of labor at term prior to caesarean delivery, and for the treatment of dysmenorrhea. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.
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- Novel hydroxy cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
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The present invention provides substituted 10,11-Dihydro-5H-benzo[e]-pyrrolo[1,2-a][1,4]diazepine and 9,10-Dihydro-4H-3a,5,9-triaza-benzo[f]azulene compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including prevention and/or suppression of preterm labor, suppression labor at term prior to caesarean deliver, and for the treatment of dysmenorrhea. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals.
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- Novel cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators
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The present invention provides novel tricyclic diazepine compounds and methods and pharmaceutical compositions utilizing them for the treating or preventing disorders including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleedi
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- Dopamine D3 and D4 receptor antagonists: synthesis and structure--activity relationships of (S)-(+)-N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-4- [(cyclopropylcarbonyl) amino]-2-methoxybenzamide (YM-43611) and related compounds.
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In this study, we synthesized a series of (S)-N-(3-pyrrolidinyl)benzamide derivatives, 1, 2a-d, 5a-1, and 7, and their enantiomers, (R)-1 and (R)-5c-e, and evaluated their binding affinity for cloned dopamine D2, D3, and D4 receptors and their inhibitory
- Ohmori,Maeno,Hidaka,Nakato,Matsumoto,Tada,Hattori,Sakamoto,Tsukamoto,Usuda,Mase
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p. 2764 - 2772
(2007/10/03)
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- Dibenzofurancarboxamides and their pharmaceutical compositions and methods
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This invention is directed to certain dibenzofurancarboxamides and their use as 5HT3 antagonists having unique CNS, anti-emetic and gastric prokinetic activity void of any significant D2 receptor binding properties. This invention also describes novel processes necessary for their preparation.
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