- MODIFIED PROTEINS AND PROTEIN DEGRADERS
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Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.
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Paragraph 00785-00787
(2021/12/08)
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- COLORING COMPOSITION, INKJET INK, AND TEXTILE PRINTING METHOD
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PROBLEM TO BE SOLVED: To provide: a coloring composition excellent in cyan optical density (OD value) and light fastness, an inkjet ink containing the coloring composition, and a textile printing method using the coloring composition or the inkjet ink. SOLUTION: The invention provides: a coloring composition containing a compound represented by the general formula (1) described in the specification; an inkjet ink containing the coloring composition; and a textile printing method using the coloring composition or the inkjet ink. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0161-0163
(2017/10/13)
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- Cu nanoparticles: a highly efficient non-noble metal catalyst for rapid reduction of nitro compounds to amines with NaBH4 in water
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The purely aqueous-phase reduction of a wide range of nitro compounds to the corresponding amines has been carried out with NaBH4 in the presence of inexpensive Cu nanoparticles as catalyst. The reactions were taken place in water (80?°C) within 4–15?min to give amines in high to excellent yields.
- Zeynizadeh, Behzad,Zabihzadeh, Mehdi,Shokri, Zahra
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p. 1487 - 1492
(2016/07/06)
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- Polymethylhydrosiloxane derived palladium nanoparticles for chemo- and regioselective hydrogenation of aliphatic and aromatic nitro compounds in water
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Chemo- and regioselective hydrogenation of a wide range of aliphatic, unsaturated, aromatic and heteroaromatic nitro compounds into their corresponding amines has been achieved with highly efficient polysiloxane-stabilised "Pd" nanoparticles on NAP-magnesium oxide supports using an environmentally friendly hydrogenating agent, polymethylhydrosiloxane [PMHS] in water. Highly stable and active Pd nanoparticles were prepared by the reduction of NAP-Mg-PdCl4 with PMHS, which serves as a reducing agent as well as a capping agent. The well-dispersed palladium nanoparticles on NAP-MgO catalysts also exhibit excellent regioselectivity in the hydrogenation of dinitrobenzenes to the corresponding nitroanilines. The catalyst has high durability against sintering during the hydrogenation reaction and can be reused with no loss in its activity. This journal is the Partner Organisations 2014.
- Damodara, Dandu,Arundhathi, Racha,Ramesh Babu, T. Venkata,Legan, Margaret K.,Kumpaty, Hephzibah J.,Likhar, Pravin R.
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p. 22567 - 22574
(2014/06/23)
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- NON-ANNULATED THIOPHENYLAMIDES AS INHIBITORS OF FATTY ACID BINDING PROTEINI(FABP) 4 AND/OR 5
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The invention provides novel compounds having the general formula (I), wherein R1, R2, R3, R4, R5, R6 , R7, A, E and n are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 64
(2014/04/03)
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- PROCESSES FOR THE PREPARATION OF THIETANAMINE
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The present invention provides processes for the preparation of compounds of formula (I) including processes comprising a. reacting a compound of formula (II) with a nucleophile in the presence of water to give a compound comprising a thietane moiety in which the carbon atom at the 3 position of the thietane moiety is bonded to a nitrogen atom; wherein the nucleophile is selected the group consisting of: N3-, a sulfonamide having two hydrogen atoms bound to the nitrogen atom, a diimide having a hydrogen atom bound to the nitrogen atom or an anion thereof, NH2OH and NH3; and b. when the nucleophile used in step a. is N3- or NH2OH, reacting the compound produced in step a. with a suitable reducing agent to give a compound of formula (I); or when the nucleophile used in step a. is a sulfonamide, reacting the compound produced in step a. with a reagent suitable for cleaving the S-N bond of the sulfonamide group to give a compound of formula (I); or when the nucleophile used in step a. is a diimide, reacting the compound produced in step a. with a reagent suitable for cleaving the C-N bond of the amide group to give a compound of formula (I). The invention also relates to intermediates useful for the preparation of compounds of formula (I).
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Page/Page column 33
(2013/03/26)
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- PROCESS FOR THE PREPARATION OF THIETANE DERIVATIVES
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The present invention relates to processes for the preparation of thietane derivatives of the formula (IA) and thietane derivatives of the formula (IB) wherein R1, R2, A1, A2, A3, A4, B, and n are as defined in the claims. The invention also relates to intermediates useful in the processes, as well as the compounds of formula (IA) and (IB) and their use as pesticides.
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Page/Page column 57
(2013/03/26)
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- A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro
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Recently, the World Health Organization approved the nifurtimox- eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, ～1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.
- Zhou, Linna,Stewart, Gavin,Rideau, Emeline,Westwood, Nicholas J.,Smith, Terry K.
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supporting information
p. 796 - 806
(2013/03/28)
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- Copper(I)-catalyzed amination of aryl halides in liquid ammonia
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The amination of aryl halides in liquid ammonia (LNH3) is catalyzed by a copper(I) salt/ascorbate system to yield primary aromatic amines in good to excellent yields. The low concentrations of catalyst required and the ease of product isolation suggest that this process has potential industrial applications. Commonly used ligands for analogous metal-catalyzed reactions are not effective. The rate of amination of iodobenzene in liquid ammonia is first order in copper(I) catalyst concentration. The small Hammett I? = 0.49 for the amination of 4-substituted iodobenzenes in liquid ammonia at 25 °C indicates that the C-I bond is not significantly broken in the transition state structure and that there is a small generation of negative charge in the aryl ring, which is compatible with the oxidative addition of the copper ion being rate limiting.
- Ji, Pengju,Atherton, John H.,Page, Michael I.
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p. 7471 - 7478
(2012/11/06)
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- Simple and efficient CuI/PEG-400 system for amination of aryl halides with aqueous ammonia
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The cross-coupling reaction between aryl halides with aqueous ammonia was efficiently catalyzed in CuI/PEG-400 System with high yield. A range of electron-withdrawing or electron-donating aryl iodides and bromides were found to be applicable to the environmentally benign system. The process allows assembly of primary arylamines in great diversity which bear a wide range of functional groups including cyano, nitro, acetyl, ether, or amino moiety.
- Chen, Junmin,Yuan, Tangjun,Hao, Wenyan,Cai, Mingzhong
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experimental part
p. 3710 - 3713
(2011/08/06)
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- CYCLOPROPANE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
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Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.
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Page/Page column 100
(2010/05/14)
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- Solid-phase synthesis of aryl, heteroaryl, and sterically hindered alkyl amines using the Curtius rearrangement
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An efficient method for the solid-phase synthesis of aryl amines, heteroaryl amines, and sterically hindered alkyl amines has been developed. The key step in this process was the formation of resin-bound carbamates (B) by the Curtius rearrangement of aryl
- Sunami, Satoshi,Ohkubo, Mitsuru
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experimental part
p. 638 - 643
(2009/04/06)
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- Cross-coupling of aryl/heteroaryl bromides with ammonia using a copper-carbene catalyst
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A variety of aryl and heteroaryl bromides were cross-coupled with ammonia in good to high yields in the presence of a copper-NHC catalyst. The Royal Society of Chemistry.
- Ntaganda, Rukundo,Dhudshia, Bhartesh,Macdonald, Charles L. B.,Thadani, Avinash N.
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supporting information; experimental part
p. 6200 - 6202
(2009/05/06)
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- Ammonium salts as an inexpensive and convenient nitrogen source in the Cu-catalyzed amination of aryl halides at room temperature
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Convenient and inexpensive ammonium salts such as NH4Cl and aqueous NH3 solution are found to be readily utilized in the Cu-catalyzed room temperature N-arylation of aryl halides, providing N-unprotected aniline derivatives in high yields. The Royal Society of Chemistry.
- Kim, Jinho,Chang, Sukbok
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supporting information; scheme or table
p. 3052 - 3054
(2009/02/04)
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- Methods for inhibiting protein kinases
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The present invention provides methods for inhibiting protein kinases selected from the group consisting of AKT, Checkpoint kinase, Aurora kinase, Pim-1 kinase, and tyrosine kinase using imidazo[1,2-a]pyrazine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with protein kinases using such compounds.
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Page/Page column 151
(2010/11/27)
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- Imidazopyrazines as protein kinase inhibitors
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In its many embodiments, the present invention provides a novel class of imidazopyrazine compounds as inhibitors of protein and/or checkpoint kinases, methods of preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of preparing pharmaceutical formulations including one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the protein or checkpoint kinases using such compounds or pharmaceutical compositions.
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Page/Page column 77
(2010/11/27)
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- Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus
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The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
- Xie, Hui,Ng, Danny,Savinov, Sergey N.,Dey, Barna,Kwong, Peter D.,Wyatt, Richard,Smith III, Amos B.,Hendrickson, Wayne A.
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p. 4898 - 4908
(2008/03/11)
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- Palladium-catalyzed silane/siloxane reductions in the one-pot conversion of nitro compounds into their amines, hydroxylamines, amides, sulfonamides, and carbamates
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A combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS) facilitates the room-temperature reduction of aromatic nitro compounds to anilines. These reactions tend to be quick (30 min), high-yielding, and tolerate a range of other functional groups. Replacement of PMHS/KF with triethylsilane allows for the reduction of aliphatic nitro compounds to their corresponding hydroxylamines. Depending on the substrate, both conditions can allow for the in situ conversion of the product amines into amides, sulfonamides, and carbamates. Georg Thieme Verlag Stuttgart.
- Rahaim Jr., Ronald J.,Maleczka Jr., Robert E.
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p. 3316 - 3340
(2008/09/17)
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- Pd-catalyzed silicon hydride reductions of aromatic and aliphatic nitro groups
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(Chemical Equation Presented) Room-temperature reduction of aromatic nitro groups to amines can be accomplished in high yield, with wide functional group tolerance and short reaction times (30 min) using a combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS). Replacing PMHS/KF with triethylsilane allows aliphatic nitro groups to be reduced to their hydroxylamines.
- Rahaim Jr., Ronald J.,Maleczka Jr., Robert E.
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p. 5087 - 5090
(2007/10/03)
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- 4-Oxo-4,7-dihydrothieno[2,3-b]pyridines as non-nucleoside inhibitors of human cytomegalovirus and related herpesvirus polymerases
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A novel series of 4-oxo-4,7-dihydrothieno[2,3-6]pyridine-5-carboxamides have been identified as potential antivirals against human herpesvirus infections resulting from human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). Compounds 10c and 14 demonstrated broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, and VZV. High specificity for the viral polymerases was observed compared to human α polymerase. The antiviral activity of 10c and 14, as determined by plaque reduction assay, was comparable or superior to that of existing antiherpes drugs, ganciclovir (for HCMV) and acyclovir (for HSV-1 and VZV). Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy. In addition, compound 14 maintained potent antiviral activity against acyclovir-resistant HSV-1 strains. Substitution to the pyridone nitrogen (N7) was found to be critical for enhanced in vitro antiviral activity.
- Schnute, Mark E.,Cudahy, Michele M.,Brideau, Roger J.,Homa, Fred L.,Hopkins, Todd A.,Knechtel, Mary L.,Oien, Nancee L.,Pitts, Thomas W.,Poorman, Roger A.,Wathen, Michael W.,Wieber, Janet L.
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p. 5794 - 5804
(2007/10/03)
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- Synthesis of primary amines and N-methylamines by the electrophilic amination of Grignard reagents with 2-imidazolidinone O-sulfonyloxime
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2-Imidazolidinone O-sulfonyloxime reacts with various aryl and alkyl Grignard reagents as an electrophilic amination reagent, giving N-alkylated imines. The resulting imines are transformed to primary amines and N-methyl secondary amines by hydrolysis with CsOH and LiAlH4 reduction, respectively.
- Kitamura, Mitsuru,Chiba, Shunsuke,Narasaka, Koichi
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p. 1063 - 1070
(2007/10/03)
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- Potent and selective inhibitors of PDGF receptor phosphorylation. 2. Synthesis, structure activity relationship, improvement of aqueous solubility, and biological effects of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives
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4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieties, and the piperazine moiety were investigated. The role of the linker was found to be quite different, where ureas yielded decreasing activity, while thioureas provided increasing activity. Cyanoguanidine as a bioisostere of thiourea and related dicyanovinyl or nitrovinyl groups were not suitable for potent activity. A hydrogen atom on the (thio)urea moiety was essential for activity. Stereochemistry was also important for inhibition of PDGFR phosphorylation. Through the modification of these moieties, benzylthiourea analogues with a small substituent on the 4-position and the 3,4-methylenedioxy group (KN734/CT52923) were found to be optimal for selective and potent activity. Replacement of the phenyl ring by heterocycles improved aqueous solubility without loss of activity and kinase selectivity. Introduction of a methyl group on 5-position of the piperazine ring and replacement by homopiperazine reduced inhibitory activity. An efficient synthetic method was also developed for 2-pyridylurea-containing analogues, via carbonylation of 2-aminopyridine with N,N′-carbonyldiimidazole. A potent analogue, KN734, inhibited smooth muscle cell proliferation and migration induced by platelet derived growth factor-BB (PDGF-BB) and suppressed neointima formation following balloon injury in rat carotid artery by oral administration. Therefore, 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives may be expected to have potential as therapeutic agents for the treatment of restenosis.
- Matsuno, Kenji,Nakajima, Takao,Ichimura, Michio,Giese, Neill A.,Yu, Jin-Chen,Lokker, Nathalie A.,Ushiki, Junko,Ide, Shin-ichi,Oda, Shoji,Nomoto, Yuji
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p. 4513 - 4523
(2007/10/03)
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- Inhibition of raf kinase activity using aryl ureas
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Methods of treating tumors mediated by raf kinase, with substituted urea compounds, and such compounds per se.
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- Aromatic heterocyclic compounds and their use as anti-inflammatory agents
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Novel aromatic heterocyclic compounds inhibit cytokines production involved in immunoregulation and inflammation such as interleukin-1 and tumor necrosis factor production. The compounds are therefore useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases.
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- Solid phase synthesis of aryl and heteroaryl amines using the Curtius rearrangement
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An efficient method for the solid phase synthesis of secondary aryl amines and heteroaryl amines was developed. The key step was the formation of aryl or heteroaryl carbamates using the Curtius rearrangement of aryl carboxylic acids with Wang resin as a trapping hydroxyl group. N-alkylation reactions of resin-bound carbamates under the Mitsunobu condition or using sodium hydride gave secondary aryl or heteroaryl amines in good yields. The developed method can be applied in the preparation of libraries containing aryl and heteroaryl amine structures as a pharmacophore.
- Sunami, Satoshi,Sagara, Takeshi,Ohkubo, Mitsuru,Morishima, Hajime
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p. 1721 - 1724
(2007/10/03)
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- DIARYL 5,6-FUSED HETEROCYCLIC ACIDS AS LEUKOTRIENE ANTAGONISTS
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Compounds having the formula I: STR1 are antagonists of the actions of leukotrienes. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
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- New diazepines substituted in the 6-position, processes for their preparation and their use as pharmaceutical compositions
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The invention relates to new diazephines of the formula STR1 wherein R 1, R 2 and R 3 are as defined herein, processes for preparing them and their use as pharmaceutical compositions useful for treating PAF-induced disease.
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- 4,7-dihydrothieno[2,3-B]pyridine derivatives useful in the treatment of cardiovascular diseases
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Highly effective calcium channel blockers having potent antihypertensive and coronary vasodilating actions, i.e. 4,7-dihydrothieno[2,3-b]pyridine derivatives of the formula: STR1 wherein R 1 is straight or branched chain C 1 -C 4 alkyl, alkoxyalkyl, or arylalkyl; R 2 is hydrogen, straight or branched chain C 1 -C 4 alkyl, or alkoxycarbonyl; R 3 is hydrogen, straight or branched chain C 1 -C 4 alkyl, phenyl which may be substituted by one or more halogens or alkoxy groups, optionally substituted cycloalkyl, or optionally substituted cycloalkylalkyl; or R 2 and R 3 taken together may form an alkylene.
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- Preparation of esters of phosphorus acids
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Esters of phosphorus acids are prepared by an improved process whereby aromatic alcohols and phosphorus halides are reacted at specified temperatures in the presence of amine catalysts thereby providing high yields of substantially pure esters and allowing preparation of selected halogen-containing mono- and di-esters of phosphorus acids wherein halogen is directly bonded to phosphorus having substantially no side reactant contamination. The phosphorus esters are useful as intermediates in the preparation of plasticizers, oil additives and functional fluids.
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