- Novel and efficient method to synthesize N-benzyl-4-formyl-piperidine
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A novel and efficient method was developed to synthesize N-benzyl-4-formyl-piperidine, a key intermediate of Donepezil (Aricept). N-Benzyl-4-piperidone was reacted with dimethyloxosulfonium methylide to get epoxide, followed by rearrangement in the presence of magnesium bromide etherate to give target compound in high yield.
- Sheng, Rong,Hu, Yongzhou
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Read Online
- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
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Paragraph 0315; 0320-0322
(2021/04/23)
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- 4-Aryl-1-oxa-4,9-diazaspiro[5.5]undecane Derivatives as Dual μ-Opioid Receptor Agonists and σ1 Receptor Antagonists for the Treatment of Pain
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The synthesis and pharmacological activity of a new series of 1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the sigma-1 receptor (σ1R) and the μ-opioid receptor (MOR) are reported. The different positions of the central scaffold, designed using a merging strategy of both target pharmacophores, were explored using a versatile synthetic approach. Phenethyl derivatives in position 9, substituted pyridyl moieties in position 4 and small alkyl groups in position 2 provided the best profiles. One of the best compounds, 15au, showed a balanced dual profile (i.e., MOR agonism and sigma antagonism) and a potent analgesic activity, comparable to the MOR agonist oxycodone in the paw pressure test in mice. Contrary to oxycodone, as expected from the addition of σ1R antagonism, 15au showed local, peripheral activity in this test, which was reversed by the σ1R agonist PRE-084. At equianalgesic doses, 15au showed less constipation than oxycodone, providing evidence that dual MOR agonism and σ1R antagonism may be a useful strategy for obtaining potent and safer analgesics.
- García, Mónica,Virgili, Marina,Alonso, Mònica,Alegret, Carles,Fernández, Bego?a,Port, Adriana,Pascual, Rosalía,Monroy, Xavier,Vidal-Torres, Alba,Serafini, María-Teresa,Vela, José Miguel,Almansa, Carmen
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p. 2434 - 2454
(2019/12/25)
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- ANTIMICROBIAL COMPOUNDS AND METHODS
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The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
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Paragraph 00323
(2020/07/31)
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- Continuous Flow Synthesis of Terminal Epoxides from Ketones Using in Situ Generated Bromomethyl Lithium
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A scalable procedure for the direct preparation of epoxides from ketones has been developed. The method is based on the carefully controlled generation of (bromomethyl)lithium (LiCH2Br) from inexpensive CH2Br2 and MeLi in a continuous flow reactor. The reaction has shown excellent selectivity for a variety of substrates, including α-chloroketones, which typically fail under classic Corey-Chaykovsky conditions. This advantage has been used to develop a novel route toward the drug fluconazole.
- Von Keutz, Timo,Cantillo, David,Kappe, C. Oliver
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supporting information
p. 10094 - 10098
(2019/12/24)
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- Deuterated antidepressant medicine
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The invention provides a compound represented by a structural formula I and a non-toxic pharmaceutically acceptable salt and use thereof in preparation of medicine for treatment of depression. In theformula I shown in the description, R1, R2, R3 and R4 are independent H or deuterium (D) separately, and meanwhile, at least one of the R1, R2, R3 and R4 must be D.
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- NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Provided are 2-(piperidin-1-yl)pyrimidin-4(3H)-ones or pharmaceutically acceptable salts thereof, each characterized by having a 1,8-diazaspiro[4.5]deca-3-ene, 1-oxa-8-azaspiro[4.5]deca-3-ene, 2,8-diazaspiro[4.5]deca-3-ene, 2-oxa-8-azaspiro[4.5]deca-3-ene, 2,9-diazaspiro[5.5]undeca-3-ene, 1-oxa-9-azaspiro[5.5]undeca-3-ene, 1,9-diazaspiro[5.5]undeca-4-ene, or 3,9-diazaspiro[5.5]undeca-1-ene structure represented by the following general formula (1):
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Paragraph 0200; 0201
(2019/05/16)
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- SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
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Provided herein are compounds of the Formula I: (I) or pharmaceutically acceptable salt or solvate thereof, wherein A, B, X1, X2, X3, X4, Ring D, E, Ra, Rb, n and m have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.
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Paragraph 002332; 002334
(2018/04/27)
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- Synthesis of Functionalized 1,4-Dioxanes with an Additional (Hetero)Aliphatic Ring
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An approach to the preparation of 2-mono-, 2,2- and 2,3-disubstituted 1,4-dioxane derivatives is described. The reaction sequence commences from readily available epoxides, in most cases prepared via the Corey-Chaikovsky reaction of the corresponding aldehydes and ketones. The key step of the method is epoxide ring opening with ethylene glycol monosodium salt, followed by further cyclization of the diols obtained. The utility of the approach was demonstrated by multigram preparation of novel functionalized 1,4-dioxanes bearing additional cycloalkane, piperidine or pyrrolidine rings, mostly spirocyclic compounds, which are advanced building blocks for medicinal chemistry.
- Bondarenko, Andriy V.,Tolmachev, Andrey A.,Vashchenko, Bohdan V.,Grygorenko, Oleksandr O.
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p. 3696 - 3707
(2018/09/14)
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- N-(HETERO)ARYL-SUBSTITUTED HETEROYCLIC DERIVATIVES USEFUL FOR THE TREATMENT OF DISEASES OR CONDITIONS RELATED TO THE CENTRAL NERVOUS SYSTEM
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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R1, R2, R3, R4, R9a, R9b, R9c, R9d, R9e, R9f, m, n, A, L and B are as defined herein.
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Page/Page column 54
(2016/04/20)
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- Spirocyclic derivatives
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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R1, R2, R3, R4, R5, R6, R9, R10, Q, X, Y, Z, A, L, B, m, n and p are as defined herein.
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Page/Page column 75; 76; 78
(2016/04/09)
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- 2-[BIS(4-FLUOROPHENYL)METHYL]-2,7-DIAZASPIRO[4.5]DECAN-10-ONE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE HUMAN DOPAMINE-ACTIVE-TRANSPORTER (DAT) PROTEIN FOR THE TREATMENT OF E.G. ATTENTION DEFICIT DISORDER (ADD)
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The present invention provides compounds of formula (I) and in particular 2-[bis(4-fluorophenyl)methyl]-2,7- diazaspiro[4.5]decan-10-one derivatives and related compounds as inhibitors of human dopamine-active-transporter (DAT) protein for the treatment of sexual dysfunction, affective disorders, anxiety, depression, chronic fatigue, Tourette syndrome, Angelman syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), obesity, pain, obsessive-compulsive disorder, movement disorders, CNS disorders, sleep disorders, narcolepsy, conduct disorder, substance abuse (including smoking cessation), eating disorders, and impulse control disorders.
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Page/Page column 101
(2016/04/09)
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- ALKYL AND ARYL DERIVATIVES OF 1-OXA-4,9-DIAZASPIRO UNDECANE COMPOUNDS HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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The present invention relates to compounds of general formula (I) having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to diazaspiro undecane compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
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Page/Page column 169; 170
(2015/12/30)
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- HEPATITIS B ANTIVIRAL AGENTS
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Provided herein are compounds useful for the treatment of HBV infection in man.
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Paragraph 0257; 0258; 0259
(2014/09/30)
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- 1-[(4-HYDROXYPRIDIN-4-YL) METHYL]PYRIDINE-2(1H)-ONE DERIVATIVES, PREPARATION METHODS AND USES THEREOF
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Provided are N-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives represented by formula I, stereoisomers, pharmaceutically acceptable salts or solvates thereof
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- 1-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives, preparation methods and uses thereof
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Provided are N-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives represented by formula I, stereoisomers, pharmaceutically acceptable salts or solvates thereof. The above compounds have the dual activities of 5-hydroxytryptamine 1A receptor ligand and selective serotonin reuptake inhibitor. The preparation methods of the above compounds, the uses of these compounds for the prevention or treatment of nervous system diseases related to 5-hydroxytryptamine system dysfunction and the pharmaceutical compositions containing these compounds are also provided.
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- HEPATITIS B ANTIVIRAL AGENTS
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The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.
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Page/Page column 258
(2013/07/05)
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- Synthesis and biological evaluation of novel piperidin-4-ol derivatives
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A series of novel piperidin-4-ol derivatives were designed, synthesized, and evaluated for potential treatment of HIV. The compounds were obtained via an efficient synthetic route in excellent yields and have been characterized by 1H NMR, 13C NMR, MS, and elemental analysis. The CCR5 antagonistic activities of the compounds have also been evaluated.
- Weng, Zhiyong,Wei, Wei,Dong, Xiaowu,Hu, Yongzhou,Huang, Shufang,Liu, Tao,Xie, Xin
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scheme or table
p. 303 - 308
(2012/07/03)
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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 37
(2008/06/13)
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- QUINOLONE ANTIBACTERIAL AGENTS
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Compounds of formula (I, II, III, IV, V, and VI) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compounds of formula (I) as disclosed herein can be used in a variety of applications including use as antibacterial agents.
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Page/Page column 85; 106
(2010/02/11)
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- NOVEL TRICYCLIC SPIROPIPERIDINES OR SPIROPYRROLIDINES
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The invention provides compounds of formula (I) wherein m, R1, n, R2, q, X, Y, Z, R3, R4, R5, R6, R7, R8, t and R9 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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- 4-HYDROXPIPERIDINE DERIVATIVE WITH ANALGETIC ACTIVITY
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A compound represented by the following Formula (I): (wherein A represents oxygen atom or -NR3- (R3 represents hydrogen atom or lower alkyl group); R1 represents nitro group, lower alkoxycarbonyl group, carbamoyl group unsubstituted or mono- or di-substituted by lower alkyl group, unprotected or protected hydroxyl group, unprotected or protected carboxyl group, lower alkyl group substituted by unprotected or protected hydroxyl group, or tetrazolyl group; and R2 represents hydrogen atom, cyano group or lower alkylsulfonyl group, provided that when A is - NR3-, it is excluded that R1 represents unprotected or protected hydroxyl group or lower alkyl group substituted by unprotected or protected hydroxyl group) or its salt, and method for producing the compound, and a pharmaceutical composition containing the compound as active ingredient.
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- SYNTHESIS AND STEREOCHEMISTRY OF 1-OXA-6-HETERASPIROOCTANES. SINGLE-CRYSTAL ANALYSIS OF 6-PHENYL-1-OXA-6-PHOSPHASPIROOCTANE 6-SULFIDE
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The synthesis of several 1-oxa-6-heteraspirooctanes is reported herein for the first time.Stereochemical analysis via NMR studies and a single crystal X-ray diffraction analysis of 6-phenyl-1-oxa-6-phosphaspirooctane 6-sulfide have been completed and provide the basis for correlations of structures for other members of the families yet unknown.Epoxidation of cis-2,6-diphenyl-4-thianone with dimethyl-oxosulfonium methylide in DMSO led, surprisingly, to a tertiary alcohol, presumably via ring opening of the expected intermediate epoxide.This is the first example of this type of ring opening in the presence of this base but the reaction time was longer than that normally employed in this process.Since the family members of the parent spirooctanes are rare, an X-ray diffraction analysis was performed on 6-phenyl-1-oxa-6-phosphaspirooctane 6-sulfide.This analysis revealed a space group of Pna21 with cell dimensions of: a=13.056(3) Angstroem, b=14.268(3) Angstroem, and c=6.1522(11) Angstroem.The phosphorinane ring assumes a slightly flattened chair conformation with the phenyl-P bond being equatorial and the P=S bond being axial.The plane of the epoxide is virtually coincident with a pseudo-mirror plane through P(6), C(3), C(9) and S(15).The phenyl group is rotated out of this plane by 28.2 deg.Although the P-C distances (ring carbons) are 1.813(3) Angstroem and 1.819(3) Angstroem, respectively, and appear to be about normal, the P-phenyl bond of 1.813(3) Angstroem is longer than in a few model systems.The C(3)-O(1) bond in the epoxide is axial or rather pseudo axial.Ring deformations are consistent with a few model epoxides the structures of which have been identified.
- Satyamurthy, Nagichettiar,Berlin, K. Darrell,Hossain, M. Bilayet,Helm, Dick van der
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p. 113 - 130
(2007/10/02)
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