- Novel approach to the synthesis of (R,S)-baclofen via PD(II)-bipyridine - Catalyzed conjugative addition
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Synthesis of (R,S)-baclofen is described starting from N- phthalimidoacetaldehyde. The key step in the synthesis was Pd(II)-bipyridine- catalyzed conjugative addition of 4-chloroboronic acid. Copyright Taylor & Francis Group, LLC.
- Varala, Ravi,Adapa, Srinivas R.
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- Structural characterization and Hirshfeld surface analysis of racemic baclofen
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The crystal structure of baclofen, (R,S) [4-amino-3-(4-chlorophenyl)butanoic acid], (C10H12ClNO2, Mr = 213.66) has been determined by single crystal X-ray diffraction analysis. The title compound crystallizes in the orthorhombic space group Pbca (No. 61) with a = 9.2704(5), b = 7.0397(4), c = 30.4015(15) ?, V = 1984.0(2) ?3 and Z = 8. The molecules exist as zwitterions, adopting a gauche conformation with respect to the Cα-Cβ bond, and held in a cross-linked chain arrangement by strong N-H?O hydrogen bonds and C-Cl?π interactions. The electrostatic molecular potential as well as the intermolecular interactions of the title compound were analyzed by the Hirshfeld surfaces. The FT-IR spectrum is also reported. The DTA, TG and DTG results indicate that baclofen is stable up to 205 °C.
- Maniukiewicz, Waldemar,Oracz, Monika,Sieroń, Les?aw
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- Photocatalysis Enables Visible-Light Uncaging of Bioactive Molecules in Live Cells
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The photo-manipulation of bioactive molecules provides unique advantages due to the high temporal and spatial precision of light. The first visible-light uncaging reaction by photocatalytic deboronative hydroxylation in live cells is now demonstrated. Using Fluorescein and Rhodamine derivatives as photocatalysts and ascorbates as reductants, transient hydrogen peroxides were generated from molecular oxygen to uncage phenol, alcohol, and amine functional groups on bioactive molecules in bacteria and mammalian cells, including neurons. This effective visible-light uncaging reaction enabled the light-inducible protein expression, the photo-manipulation of membrane potentials, and the subcellular-specific photo-release of small molecules.
- Wang, Haoyan,Li, Wei-Guang,Zeng, Kaixing,Wu, Yan-Jiao,Zhang, Yixin,Xu, Tian-Le,Chen, Yiyun
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supporting information
p. 561 - 565
(2019/01/04)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF BACLOFEN AND ITS INTERMEDIATE
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The present invention provides an improved process for the preparation of 3-(4-chlorophenyl)-3- cyanopropanoic acid (compound (A)) and further its transformation to Baclofen (I). The process comprises reaction of compound (II) with Glyoxylic acid to obtain 3-(4-chlorophenyl)-3- cyanoacrylic acid (III); followed by the 'in- situ' reduction of (III) in the presence of a reducing agent to provide the compound (A). Alternatively, the compound (A) is obtained by the process comprising reacting 2-(4- chlorophenyl)acetonitrile (II) with haloacetic acid (IV) in the presence of a base. The compound 3-(4-chlorophenyl)-3-cyanopropanoic acid (A) undergoes hydrogenation in the presence of a metal catalyst and ammonia solution to provide Baclofen (I).
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Page/Page column 17
(2017/02/09)
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- Catalytic Intermolecular Carboamination of Unactivated Alkenes via Directed Aminopalladation
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An intermolecular 1,2-carboamination of unactivated alkenes proceeding via a Pd(II)/Pd(IV) catalytic cycle has been developed. To realize this transformation, a cleavable bidentate directing group is used to control the regioselectivity of aminopalladation and stabilize the resulting organopalladium(II) intermediate, such that oxidative addition to a carbon electrophile outcompetes potential β-hydride elimination. Under the optimized reaction conditions, a broad range of nitrogen nucleophiles and carbon electrophiles are compatible coupling partners in this reaction, affording moderate to high yields. The products of this reaction can be easily converted to free ?3-amino acids and ?3-lactams, both of which are common structural motifs found in drug molecules and bioactive compounds. Reaction kinetics and DFT calculations shed light on the mechanism of the reaction and explain empirically observed reactivity trends.
- Liu, Zhen,Wang, Yanyan,Wang, Zichen,Zeng, Tian,Liu, Peng,Engle, Keary M.
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supporting information
p. 11261 - 11270
(2017/08/22)
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- A balufen green industrial production method (by machine translation)
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The invention discloses a balufen green preparation method, which belongs to the technical field of drug synthesis. The method to the chlorobenzene as a starting material, by Knoevenagel condensation, alkali hydrolysis, sub-amide, alkali hydrolysis and Hofmann degradation 5 step reaction make the consistent with the clinical pharmaceutical balufen. Raw materials of this invention extremely easy, low cost, simple synthesis operation, are basically all aqueous reaction under the condition of, environmental pollution is very small, high yield, is a brand new industrial production balufen method. (by machine translation)
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- Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
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While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
- Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
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supporting information
p. 678 - 682
(2015/03/04)
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- β-Substituted γ-butyrolactams from mucochloric acid: Synthesis of (±)-baclofen and other γ-aminobutyric acids and useful building blocks
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In the course of our exploration of the application of mucohalic acids in organic synthesis, we reported the synthesis of α,β-dihalo-α, β-unsaturated γ-butyrolactams by reductive amination of a suitable mucohalic acid and a suitable amine. However, the functionalization of the α- and/or β-halogen was found to be elusive under Suzuki conditions that worked well with the corresponding γ-lactones. Although the corresponding β-aryl derivative was obtained under some of the modified Suzuki conditions tried, the yields were found to be very low. Next, the Suzuki coupling was performed on mucochloric acid prior to the reductive amination step. By careful control of the reaction conditions, only β-substitution was achieved to yield the corresponding β-aryl mucochloric acid. This could then be converted to the corresponding β-substituted γ-butyrolactam by reductive amination with 2,4-dimethoxybenzylamine (DMB-NH2) followed by reduction by nickel boride and subsequent deprotection of the DMB group. The resulting γ-butyrolactam could either be alkylated or hydrolyzed resulting in the corresponding β-substituted γ-aminobutyric acid. This methodology was extended to synthesize (±)-baclofen in five steps starting from mucochloric acid.
- Biswas, Kallolmay,Gholap, Rajesh,Srinivas, Padakanti,Kanyal, Sachin,Sarma, Koushik Das
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p. 2538 - 2545
(2014/01/06)
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- METHODS OF TREATING FRAGILE X SYNDROME, DOWN?S SYNDROME, AUTISM AND RELATED DISORDERS
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Disclosed herein are methods of treating fragile X syndrome, fragile X-associated tremor/ataxia syndrome, Down?s syndrome and other forms of mental retardation, and/or autism comprising administering a GABA B agonist prodlug to a subject suffering therefrom. The GABAB agonist prodrugs can be compounds of Formula (I), (II) or (III) as disclosed herein
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- ALLOSTERIC PROTEIN KINASE MODULATORS
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The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.
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Page/Page column 94
(2010/04/30)
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- PAINKILLING ASSOCIATION COMPRISING A DIHYDROIMIDAZOPYRAZINE DERIVATIVE
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The invention relates to a product comprising (1R)-1-[(({2R)-2-amino-3-[(8S)-8-(cyclohexylmethyl) -2-phenyl-5,6-dihydroimidazo [1,2-a]pyrazin-7(8H)-yl]-3-oxopropyl}dithio)methyl]-2-[(8S)-8-(cyclohexylmethyl) -2-phenyl-5,6-dihydrolmidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethylamine in association with an analgesic agent selected from morphine, the similar or a morphine derivative, sodium channel inhibitors, non-steroidal antiflammatory agents (AINS), glutamatergic system inhibitors, tricycle antidepressants and gabaergic derivatives for simultaneous therapeutic use which is separated or out over the time for pain treatment or prevention.
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- Use of GABA and GABAB agonists
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The present invention provides methods of stimulating tissue growth, including islet cell growth, by administering GABA or a GABA agonist to act on GABAB receptors and GABAB-like receptors to activate cell replication.
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- Use of GABAB receptor agonists as reflux inhibitors
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PCT No. PCT/SE97/01555 Sec. 371 Date Nov. 12, 1997 Sec. 102(e) Date Nov. 12, 1997 PCT Filed Sep. 15, 1997 PCT Pub. No. WO98/11885 PCT Pub. Date Mar. 26, 1998The present invention relates to the use of GABAB receptor agonists for the inhibition of transient lower esophageal sphincter relaxations, and for the treatment of gastro-esophageal reflux disease.
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