- NCBSI/KI: A Reagent System for Iodination of Aromatics through in Situ Generation of I-Cl
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In situ iodine monochloride (I-Cl) generation followed by iodination of aromatics using NCBSI/KI system has been developed. The NCBSI reagent requires no activation due to longer bond length, lower bond dissociation energy, and higher absolute charge density on nitrogen. The system is adequate for mono- and diiodination of a wide range of moderate to highly activated arenes with good yield and purity. Moreover, the precursor N-(benzenesulfonyl)benzenesulfonamide can be recovered and transformed to NCBSI, making the protocol eco-friendly and cost-effective.
- Palav, Amey,Misal, Balu,Chaturbhuj, Ganesh
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p. 12467 - 12474
(2021/08/24)
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- Sulfated polyborate-H2O assisted tunable activation of N-iodosuccinimide for expeditious mono and diiodination of arenes
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Owing to both Lewis and Bronsted acid active sites on sulfated polyborate under homogenous conditions, we were keen on developing iodination protocol of arenes that can meet the requirement of regioselectivity and higher yield. The sulfated polyborate activates N-iodosuccinimide for mono iodination of highly activated substrates viz. phenols, anilines under anhydrous condition. Water tunes sulfated polyborate to generate more Bronsted acid sites resulting in rapid activation of NIS for diiodination. The protocol was equally applicable to diiodination of 4-hydroxyphenylacetic acid to synthesize 4-hydroxy-3,5-diiodophenylacetic acid, an intermediate of tiratricol, a thyroid treatment drug. This protocol was further integrated via one-pot sequential iodination and Sonogashira coupling to synthesize aryl acetylenes, building blocks for the synthesis of a variety of specialty chemicals, API, and natural products.
- Misal, Balu,Palav, Amey,Ganwir, Prerna,Chaturbhuj, Ganesh
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supporting information
(2021/05/26)
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- METHOD FOR PRODUCING AROMATIC HALOGEN DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a highly efficient and economically advantageous method for producing a halogen compound. SOLUTION: The method produces a halogen compound represented by formula (2) (X is a halogen atom, and b is an integer of 1-5) by reacting an aniline derivative represented by formula (1) (R1 is an ester group, a carbonyl group, a nitrile group, a nitro group, an optionally substituted alkyl group or an optionally substituted aralkyl group, and a is an integer of 0-4) with a halogenating agent in the presence of a copper catalyst and a persulfate. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0133-0138
(2020/07/28)
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- A novel DMSO-assisted regioselective iodination of aniline analogues
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A metal- and oxidant-free electrophilic iodination of aniline analogues was achieved in high to excellent yields at room temperature in MTBE with 0 or 3.5 equivalents of DMSO. Examined substituents include N-alkyl, N,N-dialkyl, N-morpholinyl and N-piperazinyl as well as methyl, Br, CN and CO2CH3 aryl ring substitutions.
- Bovonsombat, Pakorn,Lorpaiboon, Wanutcha,Laoboonchai, Sarocha,Sriprachaya-anunt, Prima,Yimkosol, Warangkana,Siriphatcharachaikul, Natthapatch,Siricharoensang, Pornpawit,Kangwannarakul, Terawee,Maeda, Jin,Losuwanakul, Satreerat,Mahesh Abhyankar, Maitraye
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- Synthesis of functionalized 1,2-diphenylacetylene derivatives
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A series of new functionalized 1,2-diphenylacetylene derivatives, including those containing l-prolinamide substituents at the aromatic nuclei, was synthesized using the Sonogashira coupling at the key step.
- Lozanova,Stepanov,Mel′nik,Zlokazov,Veselovsky
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- SELECTIVE ALPHA-7 NICOTINIC RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM
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In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.
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Paragraph 0212
(2018/09/16)
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- Iodine(III) Reagent-Mediated Intramolecular Amination of 2-Alkenylanilines to Prepare Indoles
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A variety of 3-substituted and 2,3-disubstituted indoles were synthesized efficiently in good yields through the intramolecular amination of 2-alkenylanilines promoted by readily available iodine(III) reagents in a short reaction time. Mechanistic studies showed that the reaction pathway went through a nitrenium ion and that 3-acetoxy indoline was the key intermediate in the indole formation. The indole product was easily prepared on a gram scale and amination also proceeded smoothly using catalytic 3,5-dimethylphenyl iodine in the presence of mCPBA. Furthermore, the indolo[3,2-a]carbazole scaffold was prepared in good yield in six steps from commercial ortho-iodoaniline. (Figure presented.).
- Zhao, Chun-Yang,Li, Kun,Pang, Yu,Li, Jia-Qing,Liang, Cui,Su, Gui-Fa,Mo, Dong-Liang
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supporting information
p. 1919 - 1925
(2018/03/28)
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- Improved method for microwave-assisted synthesis of benzodiazepine-2,5-diones from isatoic anhydrides mediated by glacial acetic acid
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An improved and simpler method for the synthesis of benzodiazepin-2,5-diones and 7-iodobenzodiazepin-2,5-diones catalyzed by glacial acetic acid using isatoic anhydride and 6-iodoisatoic anhydride, respectively, as starting materials is reported. The target products were achieved in good yields (up to 71percent) using microwave irradiation as the activating mode of reaction in the presence of acetic acid instead of the traditional polar aprotic solvents as dimethylformamide (DMF), dimethyl sulfoxide (DMSO) or dimethylacetamide (DMAC). Moreover, relatively simple purification workup is required. The optimal temperature to obtain the benzodiazepin-2,5-dione derivatives was 130 °C, while the best irradiation time was 3 min. In addition, the methodology for the selective preparation of 6-iodoisatoic anhydride with an overall yield of 62percent is presented. Printed in Brazil-
- De La Cruz, Armando,Vega-Acevedo, Carlos Alejandro,Rivero, Ignacio A.,Chávez, Daniel
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p. 1607 - 1611
(2018/06/29)
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- N-hydroxyl heterocycle pyrimindine diketone derivative and preparation method and application thereof
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The invention discloses a quinazoline ketone derivative and a preparation method and application thereof.The compound is of the structure as shown in the general formula (I).The invention further relates to a drug composition containing the compound in the formula (I).Activity screening experiments show that the compound has good anti-acne-virus and anti-adenovirus activity, and therefore application of the compound to preparing anti-acne-virus and anti-adenovirus drugs is also provided.Please see the formula (I) in the description.
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Paragraph 0052; 0055
(2016/10/09)
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- First discovery of novel 3-hydroxy-quinazoline-2,4(1H,3H)-diones as specific anti-vaccinia and adenovirus agents via ‘privileged scaffold’ refining approach
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A series of 1,2,3-triazolyl 3-hydroxy-quinazoline-2,4(1H,3H)-diones was constructed utilizing Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) method. The biological significance of the novel synthesized quinazolines was highlighted by evaluating them in vitro for antiviral activity, wherein several compounds exhibited excellent activity specifically against vaccinia and adenovirus. Especially, 24b11 displayed the most potent inhibitory activity against vaccinia with an EC50value of 1.7 μM, which was 15 fold than that of the reference drug Cidofovir (EC50= 25 μM). 24b13 was the most potent compound against adenovirus-2 with an EC50value of 6.2 μM, which proved lower than all the reference drugs. Preliminary structure–activity relationships were also discussed. To the best of our knowledge, no data are present in the literature on antiviral activity of 3-hydroxy-quinazoline-2,4(1H,3H)-diones against DNA-viruses. Thus, these findings warrant further investigations (library expansion and compound refinement) on this novel class of antiviral agents.
- Kang, Dongwei,Zhang, Heng,Zhou, Zhongxia,Huang, Boshi,Naesens, Lieve,Zhan, Peng,Liu, Xinyong
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supporting information
p. 5182 - 5186
(2016/11/09)
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- Kumada cross coupling reaction based synthesis, antimicrobial and computational studies of 6-aryl-2-phenyl-3-methylquinazolin-4(3H)-ones
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Nickel catalyzed Kumada cross coupling reaction, a novel synthetic method for the synthesis of 6-aryl-2-phenyl-3-methylquinazolin-4(3H)-ones (6a-6i), was carried out by condensing 6-iodo-2-phenyl-3-methyl-quinazolin-4(3H)-one (4) with various 6-aryl/heteroaryl Grignard reagents. Molecular properties of compounds 4 and 6a-6i were studied using semiempirical PM3 computational method. The optimized geometry of the product 6 indicated that the aryl group at the position 6 was not coplanar with respect to either quinazolinone ring or phenyl group at 2 position. Compounds 6a-6i were screened for their activity against bacteria and fungi.
- Shankaraiah,Veeresham,Bhavani
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p. 368 - 375
(2016/04/20)
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- Tandem C-O and C-N Bonds Formation Through O-Arylation and [3,3]-Rearrangement by Diaryliodonium Salts: Synthesis of N-Aryl Benzo[1,2,3]triazin-4(1H)-one Derivatives
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Metal-free O-arylation and [3, 3]-rearrangement have been shown as an efficient strategy to construct new C-O and C-N bonds in one-pot reactions. The method was used to prepare N-aryl benzo[1,2,3]triazin-4(1H)-one derivatives in good yields from N-hydroxy benzo[1,2,3]triazin-4(3H)-one and diaryliodonium salts. The reaction was tolerated a variety of sensitive functional groups such as iodine, nitro, ester, and aldehyde groups. A rational mechanism was proposed based on the experimental results, and the reaction was easily up to gram scale.
- Shi, Wei-Min,Ma, Xiao-Pan,Pan, Cheng-Xue,Su, Gui-Fa,Mo, Dong-Liang
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p. 11175 - 11183
(2015/11/18)
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- Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma
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Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with 18F or 131I/125I for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [125I]- and [18F]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([125I]4, [18F]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 ± 2.6% ID/g and 6.8 ± 1.9% ID/g, respectively).
- Billaud, Emilie M.F.,Maisonial-Besset, Aurélie,Rbah-Vidal, Latifa,Vidal, Aurélien,Besse, Sophie,Béquignat, Jean-Baptiste,Decombat, Caroline,Degoul, Fran?oise,Audin, Laurent,Deloye, Jean-Bernard,Dollé, Frédéric,Kuhnast, Bertrand,Madelmont, Jean-Claude,Tarrit, Sébastien,Galmier, Marie-Josèphe,Borel, Michèle,Auzeloux, Philippe,Miot-Noirault, Elisabeth,Chezal, Jean-Michel
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supporting information
p. 818 - 838
(2015/03/05)
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- INHIBITORS OF CDK8/19 FOR USE IN TREATING ESTROGEN RECEPTOR POSITIVE BREAST CANCER
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The invention provides a selective inhibitor of CDK8/19 for use in a method of treating a patient having estrogen receptor positive (ER+) breast cancer, including breast cancer that is resistant to antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8/19 is administered in combination with antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8/19 is administered to ER + HER2+ breast cancer patients in combination with HER2-targeting drugs.
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Page/Page column 5
(2014/09/16)
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- Facile assembly of two 6-membered fused N-heterocyclic rings: A rapid access to novel small molecules via Cu-mediated reaction
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A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4. The Royal Society of Chemistry.
- Adepu, Raju,Sunke, Rajnikanth,Meda, Chandana L. T.,Rambabu,Krishna, G. Rama,Reddy, C. Malla,Deora, Girdhar Singh,Parsa, Kishore V. L.,Pal, Manojit
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supporting information
p. 190 - 192
(2013/02/22)
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- CDK8/CDK19 SELECTIVE INHIBITORS AND THEIR USE IN ANTI-METASTATIC AND CHEMOPREVENTATIVE METHODS FOR CANCER
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The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI -related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.
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Page/Page column 18
(2013/08/15)
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- METHODS FOR PREPARING BIPHENYL BENZOIC ACID DERIVATIVES
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The present invention relates to a method for preparing biphenyl benzoic acid derivatives. The method for preparing biphenyl benzoic acid derivatives of the present invention is industrially advantageous in that: undesired intermediates are not formed because nitrogenation does not occur at the ortho- or para-position during nitrogenation reaction; Raney Ni having strong flammability is not used; and dehalogenation effect can be achieved only by reducing without a separate step for dehalogenation reaction.
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Page/Page column 10-11
(2010/07/02)
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- Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists
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Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent 45Ca2+ uptake inhibitions in rat DRG neuron with IC50s of 25, 32 and 28 nM, respectively.
- Li, Fu-Nan,Kim, Nam-Jung,Chang, Dong-Jo,Jang, Jaebong,Jang, Hannah,Jung, Jong-Wha,Min, Kyung-Hoon,Jeong, Yeon-Su,Kim, Sun-Young,Park, Young-Ho,Kim, Hee-Doo,Park, Hyeung-Geun,Suh, Young-Ger
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experimental part
p. 8149 - 8160
(2010/03/25)
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- MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS
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The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.
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Page/Page column 168-169
(2008/06/13)
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- MACROLONES
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A compound of formula (I) or a pharmaceutically acceptable derivative thereof, having antimicrobial activity, processes for their preparation, compositions containing them and to their use in medicine.
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Page/Page column 57
(2008/06/13)
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- 4-Hydroxy-2-quinolones. 90.* Synthesis and antitubercular activity of 4-methyl-2-thiazolylamides of halo-substituted 4-hydroxy-2-oxo-1,2-dihydro-3- quinolinecarboxylic acids
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Several variants were studied for the synthesis of esters of halogen derivatives of 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxylic acids, whose reaction with 2-amino-4-methylthiazole gives the corresponding hetarylamides. Results are given for a study of the antitubercular activity of these products. 2006 Springer Science+Business Media, Inc.
- Ukrainets,Sidorenko,Petrushova,Gorokhova
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- MACROLONE COMPOUNDS
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A compound of formula (I) For use as antibacterial agents, compositions containing same, processes for their preparation and their use in therapy.
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Page/Page column 48
(2010/11/30)
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- CHK-1 INHIBITORS
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Disclosed are novel inhibitors of Chk-1 and methods of using the same for therapy.
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Page/Page column 207
(2010/02/11)
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- 2, 5-DIHYDRO-PYRAZOLO`4, 3-C!QUINOLIN-4-ONES AS CHK-1 INHIBITORS
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Disclosed are novel inhibitors of Chk-1 and methods of using the same for therapy.
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Page/Page column 73
(2010/02/15)
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- ANTIBACTERIAL AGENTS
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The present invention relates to antibacterial agents that are useful for sterilization, sanitation, antisepsis, and disinfection.
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- Compounds
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The present invention relates to 2-(benzoylamino)benzoic acid derivatives of the formula I wherein the variants Ar, X and R are as described in the specification. The said compounds modulate the activity of peroxisome proliferator-activated receptors (PPAR) α and/or γ, and are predicted to be useful in the treatment of metabolic diseases, e.g. type II diabetes.
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- Iodination of aromatic amines with iodine and silver sulfate
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Iodination of aromatic amines with iodine/silver sulfate at room temperature gives iodo-products in good (46-96%) yield.
- Sy
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p. 3215 - 3219
(2007/10/02)
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- Synthesis of Some Substituted Dimethyl and Diethyl 4-(Phenylethynyl)-2,6-pyridinedicarboxylates
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Substituted dimethyl and diethyl 4-(phenylethynyl)-2,6-pyridinedicarboxylates were prepared by coupling reactions between dialkyl 4-halo-2,6-pyridinedicarboxylates and terminal arylacetylenes in the presence of an organopalladium catalyst and copper(I) iodide in a suitable solvent system.The terminal acetylenes needed in this work were synthesized from the corresponding aryl halides using either (trimethylsilyl)acetylene or 2-methyl-3-butyn-2-ol followed by deprotection of the triple bond, depending on the nature of the compound in question.
- Takalo, Harri,Kankare, Jouko,Haenninen, Elina
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p. 448 - 454
(2007/10/02)
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- Inhibitors of Cyclic AMP Phosphodiesterase. 3. Synthesis and Biological Evaluation of Pyrido and Imidazolyl Analogues of 1,2,3,5-Tetrahydro-2-oxoimidazoquinazoline
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Hybridization of structural elements of 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline ring system common to the cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitors lixazinone (RS-82856,1) and anagrelide (3) with complementary features of other PDE inhibitor cardiotonic agents prompted the design and synthesis of the title compounds 7a-d, 11, 12, and 13a,b.The necessary features of these compounds were determined within the framework of the proposed active-site models for the high affinity form of cAMP PDE inhibited by cGMP (type IV).Evaluation of these targets, both in vitro as inhibitors of platelet or cardiac type IV PDE or in vivo as inotropic agents in the pentobarbital-anesthetized dog model of congestive heart failure, showed that these structure possessed negligibly enhanced activities over the parent heterocyclic system, and remained significantly inferior to 1 in all respects.This difference is ascribed to the absence of the N-cyclohexyl-N-methylbutyramidyl-4-oxy side chain of 1.The proposal that the acidic lactam-type functionality, common to the type IV PDE inhibitor inotropic agents such as 4-6 and 8-10, mimics the polarizable cyclic phosphate moiety of cAMP suggested that the side chain of 1 may function as an effective surrogate for selected characteristics of the adenine portion of cAMP.However, the results of this study show that incorporation of adenine-like hydrogen-bonding functionalities common to other type IV PDE inhibitors into the 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline system did not enhance activity to the levels observed for 1 analogues.These observations, coupled with the kinetic pattern of inhibition of type IV PDE observed for 1 and analogues, suggest that access to a secondary, lipophilic-tolerant binding site, possibly coincident with the adenine binding domain, and adjacent to the catalytic ribose-phosphate binding site of platelet and cardiac type IV PDE, is responsible for the increased potency of these compounds.
- Venuti, Michael C.,Stephenson, Robert A.,Alvarez, Robert,Bruno, John J.,Strosberg, Arthur M.
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p. 2136 - 2145
(2007/10/02)
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- 4H-3,1-BENZOXAZIN-4-ONES AND RELATED COMPOUNDS AND USE AS ENZYME INHIBITORS
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Novel 2-amino-4H-3,1-benzoxazin-4-ones represented by the formula wherein R 1, R 2, R 3 and X are defined herein are useful as enzyme inhibitors in animals.
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