- Visible-Light-Mediated C-I Difluoroallylation with an α-Aminoalkyl Radical as a Mediator
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Herein, we report a protocol for direct visible-light-mediated C-I difluoroallylation reactions of α-trifluoromethyl arylalkenes with alkyl iodides at room temperature with an α-aminoalkyl radical as a mediator. The protocol permits efficient functionalization of various α-trifluoromethyl arylalkenes with cyclic and acyclic primary, secondary, and tertiary alkyl iodides and is scalable to the gram level. This mild protocol uses an inexpensive mediator and is suitable for late-stage functionalization of complex natural products and drugs.
- Yue, Fuyang,Dong, Jianyang,Liu, Yuxiu,Wang, Qingmin
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supporting information
p. 7306 - 7310
(2021/10/01)
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- Copper-Catalyzed Cross-Coupling between Alkyl (Pseudo)halides and Bicyclopentyl Grignard Reagents
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The development of a copper-catalyzed cross-coupling between primary and secondary (pseudo)halides and bicyclopentyl Grignard reagents is reported. Highly strained bicyclopentanes can be cross-coupled with a large panel of primary alkyl mesylates and secondary alkyl iodides. The catalytic system is simple and cheap, and the reaction is general and chemoselective.
- Andersen, Claire,Bernardelli, Patrick,Cossy, Janine,Daumas, Marc,Ferey, Vincent,Guérinot, Amandine
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supporting information
(2020/08/05)
-
- A 3 - nitro-azetidine -1 - formic acid tert-butyl synthetic method
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The invention relates to a 3 - nitro-azetidine - 1 - carboxylic acid tert-butyl synthetic method, mainly solves the industrial synthesis method not suitable for the technical problem. The invention is divided into three steps, 1st step, first of all by compound 1 in the solvent non-water reaction adding sodium borohydride in methanol to obtain compound 2, 2nd step, compound 2 with imidazole, triphenylphosphine and iodine in toluene in reaction to obtain compound 3, 3rd step, compound 3 with urea, sodium nitrite and phloroglucinol in N, N - dimethyl formamide in reaction to obtain the final compound 4, reaction as follows: .
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- Introduction of Cyclopropyl and Cyclobutyl Ring on Alkyl Iodides through Cobalt-Catalyzed Cross-Coupling
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A cobalt-catalyzed cross-coupling between alkyl iodides and cyclopropyl, cyclobutyl, and alkenyl Grignard reagents is disclosed. The reaction allows the introduction of strained rings on a large panel of primary and secondary alkyl iodides. The catalytic system is simple and nonexpensive, and the reaction is general, chemoselective, and diastereoconvergent. The alkene resulting from the cross-coupling can be transformed to substituted cyclopropanes using a Simmons-Smith reaction. The formation of radical intermediates during the coupling is hypothesized.
- Andersen, Claire,Ferey, Vincent,Daumas, Marc,Bernardelli, Patrick,Guérinot, Amandine,Cossy, Janine
-
supporting information
p. 2285 - 2289
(2019/03/29)
-
- Regioselective α-benzylation of 3-iodoazetidine via Suzuki cross-coupling
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An efficient protocol for the synthesis of α-benzyl azetidines starting from benzylboronic acid pinacol ester derivatives and 3-iodoazetidine was developed. A wide range of α-benzyl azetidine derivatives were obtained in moderate to good yields with high regioselectivity (>99%).
- Qiu, Zhenjiang,Zhu, Mingxiang,Zheng, Lu,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 1321 - 1324
(2019/04/25)
-
- An improved, gram-scale synthesis of protected 3-haloazetidines: Rapid diversified synthesis of azetidine-3-carboxylic acids
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Azetidines are increasingly important heterocycles found in a variety of natural products and pharmaceutical compounds. Protected 3-haloazetidines, widely used and versatile building blocks in medicinal chemistry, have been prepared in a one-pot, gram-scale strain-release reaction of 1-azabicyclo[1.1.0]butane from commercially available starting materials. These intermediates were subsequently used to prepare a series of high value azetidine-3-carboxylic acid derivatives including the first reported synthesis of 1-(tert-butoxy-carbonyl)-3-((trifluoromethyl)thio)azetidine-3-carboxylic acid. (Figure pressented)
- Ji, Youngran,Wojtas, Lukasz,Lopchuk, Justin M.
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p. 195 - 214
(2018/06/27)
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- 6-HYDROXY-4-OXO-1,4-DIHYDROPYRIMIDINE-5-CARBOXAMIDES AS APJ AGONISTS
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The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.
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Paragraph 0908; 0909
(2017/10/10)
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- NOVEL PYRROLIDINE COMPOUND AND APPLICATION AS MELANOCORTIN RECEPTOR AGONIST
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The present invention relates to a novel pyrrolidine compound having melanocortin receptor agonist activity or a pharmaceutically acceptable salt thereof, and to pharmaceutical applications thereof. The present invention relates to a pyrrolidine derivative represented by formula [I], wherein ring A represents an optionally substituted aryl group or the like; R1 represents an optionally substituted alkyl group or the like; R2 represents a halogen atom or the like; and R3 is an alkyl group substituted with an optionally substituted aryl group or the like, and R4 is a hydrogen atom or the like; or R3 and R4 are terminally attached to each other, and together with the nitrogen atom to which they are attached, form an optionally substituted nitrogen-containing aliphatic heterocyclic ring that may partially contain a double bond; or to a pharmaceutically acceptable salt thereof.
- -
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Paragraph 0655
(2017/04/18)
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- POLYCYCLIC ANAPLASTIC LYMPHOMA KINASE INHIBITOR
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Provided is a polycyclic inhibitor of anaplastic lymphoma kinase as represented by Formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R1, R2, R3, R4, and ring A are as defined in the description. The invention also relates to a method for preparing the compound, a pharmaceutical preparation and a pharmaceutical composition comprising the compound, and use of the compound, the pharmaceutically acceptable salt or stereoisomer thereof in manufacture of a medicament for the treatment and/or prevention of an anaplastic lymphoma kinase-mediated cancer or non-cancer related diseases.
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- HETEROARYL PYRIDONE AND AZA-PYRIDONE COMPOUNDS AS INHIBITORS OF BTK ACTIVITY
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Heteroaryl pyridone and aza-pyridone compounds of Formula I are provided, where one or two of X, X, and Xare N, and including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I foranddiagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
- -
-
Paragraph 0805; 0806
(2015/11/16)
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- Iron- and cobalt-catalyzed arylation of azetidines, pyrrolidines, and piperidines with grignard reagents
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Iron- and cobalt-catalyzed cross-couplings between iodo-azetidines, -pyrrolidines, -piperidines, and Grignard reagents are disclosed. The reaction is efficient, cheap, chemoselective and tolerates a large variety of (hetero)aryl Grignard reagents.
- Barr, Baptiste,Gonnard, Laurine,Campagne, Rmy,Reymond, Sbastien,Marin, Julien,Ciapetti, Paola,Brellier, Marie,Gurinot, Amandine,Cossy, Janine
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supporting information
p. 6160 - 6163
(2015/01/16)
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- MONOCYCLIC PYRIDINE DERIVATIVE
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The present invention provides a novel compound having FGFR inhibitory activity or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same. Specifically, the present invention provides a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein n represents 0 to 2; A represents an arylene group or a heteroarylene group; G represents a single bond, an oxygen atom or —CH2—; E represents a nitrogen-containing non-aromatic heterocycle; R1 represents an alkoxy group or the like; R2 represents a hydrogen atom or the like; and R3 represents a hydrogen atom, an alkyl group, an alkoxy group or the like, with the proviso that when E represents an azetidine ring and R2 or R3 is present on a nitrogen atom on the azetidine ring, the R2 or R3 does not represent a hydrogen atom.
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- Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors
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Phosphodiesterase 9A inhibitors have shown activity in preclinical models of cognition with potential application as novel therapies for treating Alzheimers disease. Our clinical candidate, PF-04447943 (2), demonstrated acceptable CNS permeability in rats with modest asymmetry between central and peripheral compartments (free brain/free plasma = 0.32; CSF/free plasma = 0.19) yet had physicochemical properties outside the range associated with traditional CNS drugs. To address the potential risk of restricted CNS penetration with 2 in human clinical trials, we sought to identify a preclinical candidate with no asymmetry in rat brain penetration and that could advance into development. Merging the medicinal chemistry strategies of structure-based design with parallel chemistry, a novel series of PDE9A inhibitors was identified that showed improved selectivity over PDE1C. Optimization afforded preclinical candidate 19 that demonstrated free brain/free plasma ≥1 in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF.
- Claffey, Michelle M.,Helal, Christopher J.,Verhoest, Patrick R.,Kang, Zhijun,Fors, Kristina S.,Jung, Stanley,Zhong, Jiaying,Bundesmann, Mark W.,Hou, Xinjun,Lui, Shenping,Kleiman, Robin J.,Vanase-Frawley, Michelle,Schmidt, Anne W.,Menniti, Frank,Schmidt, Christopher J.,Hoffman, William E.,Hajos, Mihaly,McDowell, Laura,Oconnor, Rebecca E.,MacDougall-Murphy, Mary,Fonseca, Kari R.,Becker, Stacey L.,Nelson, Frederick R.,Liras, Spiros
-
p. 9055 - 9068
(2013/01/15)
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- PROCESS FOR THE PREPARATION OF IODIDES
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This invention is directed to a process for the preparation of high yield alkyl or aryl iodide from its corresponding carboxylic acid using N-iodo amides.
- -
-
Page/Page column 28-30
(2012/01/05)
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- Metal-free efficient, general and facile iododecarboxylation method with biodegradable co-products
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The development of a novel, efficient and robust method for the general conversion of aliphatic and aromatic carboxylic acids to organic iodides without the use of heavy metals or strong oxidizing agents is reported. Commercially available N-iodoamides were used for both initiation and halogen donation under irradiative conditions. Isolation of the product is extremely simple and the major co-product is removed as a water-soluble biodegradable material. Copyright
- Kulbitski, Kseniya,Nisnevich, Gennady,Gandelman, Mark
-
supporting information; experimental part
p. 1438 - 1442
(2011/07/30)
-
- PYRIDONE AND AZA-PYRIDONE COMPOUNDS AND METHODS OF USE
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Pyridone and aza-pyridone compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 287; 288
(2011/11/30)
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- N-SUBSTITUTED SATURATED HETEROCYCLIC SULFONE COMPOUNDS WITH CB2 RECEPTOR AGONISTIC ACTIVITY
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This invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1, R2,R3, R4, R5, R6, R7, k, m, n, p, q, r and s are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity.
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Page/Page column 47
(2010/08/08)
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- AMINO-HETEROCYCLIC COMPOUNDS
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The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, A, and n are as defined herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in treating neurodegenerative and cognitive disorders, such as Alzheimer's disease and schizophrenia, are also provided.
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Page/Page column 11-12
(2010/08/07)
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- CYCLOBUTENEDIONE DERIVATIVES
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The present invention relates to compounds of the formula (I): to pharmaceutically acceptable salts therefore and to pharmaceutically acceptable solvates of said compounds and salts, wherein the substituents are defined herein; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly inflammatory conditions.
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Page/Page column 77
(2010/12/17)
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- Synthesis and biological activity of anticoccidial agents: 2,3-diarylindoles
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Novel 2,3-diarylindoles bearing an amine substituent at the indole 5- and 6-positions have been synthesized and evaluated as anticoccidial agents in both in vitro and in vivo assays. Both subnanomolar in vitro activity and broad spectrum in vivo potency w
- Scribner, Andrew,Moore III, Joseph A.,Ouvry, Gilles,Fisher, Michael,Wyvratt, Matthew,Leavitt, Penny,Liberator, Paul,Gurnett, Anne,Brown, Chris,Mathew, John,Thompson, Donald,Schmatz, Dennis,Biftu, Tesfaye
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scheme or table
p. 1517 - 1521
(2009/11/30)
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- QUINOLINE COMPOUNDS SUITABLE FOR TREATING DIDORDERS THAT RESPOND TO MODULATION OF THE SEROTONIN 5-HT6 RECEPTOR
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The present invention relates to novel quinoline compounds. The compounds possess valuable therapeutic properties and are particularly suitable, for treating diseases that respond to modulation of the serotonin 5-HT6 receptor. formula (I) where
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Page/Page column 37
(2008/12/04)
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- Alpha carbolines and uses thereof
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This invention provides alpha-carboline compounds of formula I: wherein R1, R2, R3, R4, R5, and x are as described in the specification. The compounds are useful for treating inflammatory diseases and
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Page/Page column 49
(2010/11/28)
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- 3-PHENYLAZETIDINE DERIVATIVES AS DOPAMINE AGONISTS
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The present invention provides for compounds of formula (I) as defined herein. These compounds are a class of dopamine agonists, more particularly a class of agonists that are selective for D3 over D2. The compounds are useful for the treatment and/or pre
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Page/Page column 41
(2010/11/25)
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- HETEROCYCLIC COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE DOPAMINE D3 RECEPTOR
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The invention relates to compounds of the formula (I) wherein n is 0, 1 or 2; G is CH2 or CHR3; R1 is H, C,-C6-alkyl, C,-C6-alkyl substituted by C3-C6-cycloalkyl, Cl-C6-hydroxyalkyl, fluorinated C,-C6-alkyl, C3-C6-cycloalkyl, fluorinated C3-C6-cycloalkyl, C3-C6- alkenyl, fluorinated C3-C6-alkenyl, formyl, acetyl or propionyl; R2, R3 and R4 are, independently of each other, H, methyl, fluoromethyl, difluoromethyl, or trifluoromethyl; A is phenylene, pyridylene, pyrimidylene, pyrazinylene, pyridazinylene or thiophenylene, which can be substituted by one ore more substituents selected from halogen, methyl, methoxy and CF3; E is NR5 or CH2, wherein R5 is H or C1 -C3-alkyl; Ar is a cyclic radical selected from the group consisting of phenyl, a 5- or 6- -membered heteroaromatic radical comprising as ring members 1, 2 or 3 heteroatoms selected from N, O and S and a phenyl ring fused to a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, where the heterocyclic ring comprises as ring members 1, 2 or 3 heteroatoms selected from N, O and S and/or 1, 2 or 3 heteroatom-containing groups each independently selected from NR8, where R8 is H, C1-C4-alkyl, fluorinated C1-C4-alkyl, C1-C4-alkylcarbonyl or fluorinated C1-C4-alkylcarbonyl, and where the cyclic radical Ar may carry 1, 2 or 3 substituents Ra, wherein the variable Ra has the meanings given in the claims and in the description; and physiologically tolerated acid addition salts thereof. The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.
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Page/Page column 132-133
(2010/11/08)
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- Treatments for female sexual dysfunction and methods for identifying compounds useful for treating female sexual dysfunction
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The present invention provides a method of treating female sexual dysfunction, the method comprising the step of administering to a patent, having or at risk of having one or more of the disorders or conditions associated with female sexual dysfunction, a therapeutically effective amount of a compound that attenuates the binding of agouti-related protein to melanocortin receptors, but does not attenuate the binding of alpha-melanocyte stimulating hormone to melanocortin receptors. The present invention also provides a method of identifying a compound that is useful for the treatment or prevention of female sexual dysfunction, the method comprising the steps of: 1) determining if a compound affects the binding of agouti-related protein to melanocortin receptors; 2) determining if a compound affects the binding of alpha-melanocyte stimulating hormone to melanocortin receptors; and 3) selecting a compound that attenuates the binding of agouti-related protein to melanocortin receptors, but does not affect the binding of alpha-melanocyte stimulating hormone to melanocortin receptors.
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- Methods of treatment and kits comprising a growth hormone secretagogue
-
The present invention relates to methods of treating bulimia nervosa, male erectile dysfunction, female sexual dysfunction, thyroid cancer, breast cancer, or ameliorating ischemic nerve or muscle damage. The present invention also relates to kits that can be used in the treatment of bulimia nervosa, male erectile dysfunction, female sexual dysfunction, thyroid cancer, breast cancer, or ameliorating ischemic nerve or muscle damage. The present invention further relates to increasing gastrointestinal motility after surgery and increasing gastrointestinal motility in patients who have been administered an agent that decreases gastrointestinal motility.
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-
- Treatment of neuropathy
-
This invention relates to the use of cyclic guanosine 3′,5′-monophosphate phosphodiesterase type five (cGMP PDE5) inhibitors, including in particular the compound sildenafil, for the treatment of neuropathy, including in particular the treatment of diabetic neuropathy.
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-
- Pharmaceutically active compounds
-
There is provided a general formula I: or a pharmaceutically or veterinarily acceptable salt or polymorph and/or solvate thereof, wherein R1 represents H; C(O)C1-C4 alkyl; C(O)aryl; C(O)heteroaryl. and which is useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (and in particular cGMP PDE5) is desired.
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-
- Novel process for the preparation of pyrazoles
-
A “one-pot” process is described herein for the production of pyrazole compounds of general formula (II) comprising the steps of reacting a compound of general formula (III) with an acylating agent in the presence of a base and an optional activating agent followed by the addition of a hydrazine compound in situ.
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-
- Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-ones and intermediates thereof
-
A process is provided for the preparation of compounds of formula (I) herein comprising reacting a compound of formula (II), (III), (IV) or (V) in the presence of-OR3 and a hydroxide trapping agent or in the case of compounds of formula (IV) reacting in the presence of an auxiliary base and a hydroxide trapping agent (i.e.-OR3 is substituted by the auxiliary base), wherein X is a leaving group and R1 to R4 are as defined.
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- Compositions and methods of treatment for conditions responsive to testosterone elevation
-
This invention relates to methods and pharmaceutical compositions useful in the treatment of conditions that are responsive to the elevation of testosterone levels in the body and the use of estrogen agonists/antagonists for the manufacture of medicaments for the treatment of conditions that are responsive to the elevation of testosterone levels in the body. The compositions are comprised of an estrogen agonist/antagonist and a pharmaceutically acceptable vehicle, carrier or diluent. These compositions are effective in treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and are effective in increasing libido in female subjects including post-menopausal women. In the case of male subject sexual dysfunction, the compositions may also include a compound which is an elevator of cyclic guanosine 3′,5′-monophosphate (cGMP). Additionally, the compositions are effective in other conditions whose etiology is a result of testosterone deficiency or which can be ameliorated by increasing testosterone levels within the body. Methods of the invention include the treatment of conditions that are responsive to elevation of testosterone levels such as treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and the increase of libido of female subjects including post-menopausal women. The methods of treatment are effective while substantially reducing the concomitant liability of adverse effects associated with testosterone administration.
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- Substituted benzoylpiperidine derivatives and their use as Neurokinin antagonists
-
The present invention provides a compound of the formula:- or a pharmaceutically acceptable acid addition salt thereof, whereinAr is phenyl substituted by 1 or 2 substituent(s) each independently selected from fluoro and chloro;X is NSO2(C1-C4 alkyl), NSO2(halo(C1-C4 alkyl)) or O;m is 0 or 1 ;n is 1 or 2;p is 1 or 2;q is 1 or 2; and r is 1 or 2, together with processes for the preparation of, intermediates used in the preparation of, compositions containing and uses of, such derivatives. The compounds have tachykinin receptor antagonist activity.
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- Synthesis of C-substituted cyclic amines using azacycloalkyl organozinc reagents
-
Azetidine and piperidine derived organozinc species have been prepared from the corresponding azacycloalkyl iodides by direct Zn insertion. They have been shown to readily undergo Pd(0) mediated cross-coupling reactions and to transmetallate with CuCN.2LiCl.
- Billotte
-
p. 379 - 380
(2007/10/03)
-