- Sulfonic acid-functionalized ordered nanoporous Na+- montmorillonite (SANM): A novel, efficient and recyclable catalyst for the chemoselective N-Boc protection of amines in solventless media
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Sulfonic acid-functionalized ordered nanoporous Na+- montmorillonite (SANM) was used as an efficient catalyst for N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions at room temperature. Various aliphatic, aromatic, heterocyclic amines and aminols were protected as their corresponding mono-carbamates in excellent yields and short reaction times. No competitive side reactions such as isocyanate, urea, and N,N-di-Boc formation were observed. The reported method is mild, chemoselective and has the advantages such as heterogeneous catalysis, low cost and the recyclability of the catalyst.
- Shirini, Farhad,Mamaghani, Manouchehr,Atghia, Seyyed Vahid
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Read Online
- BTK Inhibitors and uses thereof
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The invention discloses a bruton's tyrosine kinase (BTK) inhibitor and use thereof. Specifically, the invention provides heteroaromatic compounds or stereoisomers, geometrical isomers, tautomers, racemates, nitrogen oxides, hydrates, solvates, metabolites and pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the heteroaromatic compounds; the invention also discloses use of the heteroaromatic compounds or the pharmaceutical compositions containing the heteroaromatic compounds in preparation of medicines; the medicines can be used for treating autoimmune diseases, inflammatory diseases or proliferative diseases.
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Paragraph 1107; 1113-1115
(2020/05/02)
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- Synthesis of Cyclic N-Hydroxylated Ureas and Oxazolidinone Oximes Enabled by Chemoselective Iodine(III)-Mediated Radical or Cationic Cyclizations of Unsaturated N-Alkoxyureas
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In this study we describe the reactivity of unsaturated N-alkoxyureas in the presence of different combinations of a hypervalent iodine(III) reagent and a bromide source or TEMPO. Three complementary cyclizations can be achieved depending on the reaction conditions. On the one hand, PIFA with pyridinium bromide leads to an oxybromination reaction. On the other hand, bis(tert-butylcarbonyloxy)iodobenzene with tetrabutylammonium bromide or TEMPO triggers aminobromination or aminooxyamination reactions, respectively. Control experiments showed that the three reactions proceed through distinct mechanisms: the first process is ionic while the other two follow a radical manifold. (Figure presented.).
- Peilleron, Laure,Retailleau, Pascal,Cariou, Kevin
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supporting information
p. 5160 - 5169
(2019/11/11)
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- Discovery of orally efficacious RORγt inverse agonists. Part 2: Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives
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A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay.
- Kono, Mitsunori,Oda, Tsuneo,Tawada, Michiko,Imada, Takashi,Banno, Yoshihiro,Taya, Naohiro,Kawamoto, Tetsuji,Tokuhara, Hidekazu,Tomata, Yoshihide,Ishii, Naoki,Ochida, Atsuko,Fukase, Yoshiyuki,Yukawa, Tomoya,Fukumoto, Shoji,Watanabe, Hiroyuki,Uga, Keiko,Shibata, Akira,Nakagawa, Hideyuki,Shirasaki, Mikio,Fujitani, Yasushi,Yamasaki, Masashi,Shirai, Junya,Yamamoto, Satoshi
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p. 470 - 482
(2018/01/05)
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- Discovery of orally efficacious RORγt inverse agonists. Part 2: Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives
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A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt)inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay.
- Kono, Mitsunori,Oda, Tsuneo,Tawada, Michiko,Imada, Takashi,Banno, Yoshihiro,Taya, Naohiro,Kawamoto, Tetsuji,Tokuhara, Hidekazu,Tomata, Yoshihide,Ishii, Naoki,Ochida, Atsuko,Fukase, Yoshiyuki,Yukawa, Tomoya,Fukumoto, Shoji,Watanabe, Hiroyuki,Uga, Keiko,Shibata, Akira,Nakagawa, Hideyuki,Shirasaki, Mikio,Fujitani, Yasushi,Yamasaki, Masashi,Shirai, Junya,Yamamoto, Satoshi
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p. 470 - 482
(2019/05/09)
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- The discovery of new human coagulation factor XIa (FXIa) inhibitors by synthesis, biological evaluation, and structure-based modeling
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Factor XIa (FXIa) is an enzyme that is activated during the earliest stage of initiation of the intrinsic pathway of the blood coagulation mechanism. In this study, we attempted to discover a new FXIa inhibitor based on structure-based molecular modeling. We found that compound 16 exhibits satisfactory predicted properties while maintaining important binding interactions with FX1a.
- Lee, Myeong Hwi,Song, Ho Young,Kim, Hyoungrae,Park, Kyung Eun,Kim, Jinyeong,Park, Tae Kyo,Kim, Yong Ju,Kang, Nam Sook
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p. 1105 - 1113
(2016/07/15)
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- Heterocyclic compound
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The present invention relates to compound (I) or a salt thereof which has a ROR γ t inhibitory action. wherein each symbol is as defined in the specification.
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Paragraph 0563
(2016/10/08)
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- Preparation, characterization and application of succinimidinium hydrogensulfate ([H-Suc]HSO4) as an efficient ionic liquid catalyst for the N-Boc protection of amines
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In this work, succinimidinium hydrogensulfate ([H-Suc]HSO4), as a novel Bronsted acidic ionic liquid is prepared and characterized by studying its FT-IR, 1H NMR, 13C NMR, mass and SEM. This reagent can be used as an efficient catalyst for the N-Boc protection of amines at room temperature and neat conditions. This new method consistently has the advantages of excellent yields and short reaction times. Further, this ionic liquid can be recovered and reused for several times. This journal is
- Shirini, Farhad,Jolodar, Omid Goli,Seddighi, Mohadeseh,Borujeni, Hojatollah Takbiri
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p. 19790 - 19798
(2015/03/18)
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- Rice husk: Introduction of a green, cheap and reusable catalyst for the protection of alcohols, phenols, amines and thiols
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A mild, efficient and eco-friendly protocol for the chemoselective protection of benzylic and primary and less hindered secondary aliphatic alcohols and phenols as trimethylsilyl ethers and different types of amines as N-tert-butylcarbamates is developed using rice husk (RiH) as the catalyst. This reagent is also able to catalyze the acetylation of alcohols, phenols, thiols and amines with acetic anhydride. Easy work-up, relatively short reaction times, excellent yields and low cost, availability and reusability of the catalyst are the striking features of this methodology, which can be considered to be one of the best and general methods for the protection of alcohols, phenols, thiols and amines. In addition, the use of a green reagent in the above-mentioned reactions results in a reduction of environmental pollution and of the cost of the applied methods.
- Shirini, Farhad,Akbari-Dadamahaleh, Somayeh,Mohammad-Khah, Ali,Aliakbar, Ali-Reza
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p. 164 - 170
(2014/03/21)
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- 1,3-Disulfonic acid imidazolium hydrogen sulfate as an efficient and reusable ionic liquid catalyst for the N-Boc protection of amines
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1,3-Disulfonic acid imidazolium hydrogen sulfate is easily prepared and used as an efficient and recyclable ionic liquid for the N-Boc protection of amines at room temperature and neat conditions. This new method consistently has the advantages of excellent yields and short reaction times. Further, the catalyst can be reused and recovered for several times without loss of activity.
- Shirini, Farhad,Khaligh, Nader Ghaffari
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p. 386 - 393
(2013/03/14)
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- Succinimide sulfonic acid (SuSA): An efficient and recyclable catalyst for the chemoselective N-Boc protection of amines
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Succinimide sulfonic acid (SuSA) as a stable reagent is easily prepared by the reaction of succinimide with neat chlorosulfonic acid. This compound is able to catalyze the chemoselective conversion of amines to their corresponding N-Boc protected derivatives with (Boc)2O. All reactions were performed under mild conditions, giving the desired products in good to high yields. Springer-Verlag 2011.
- Shirini, Farhad,Khaligh, Nader Ghaffari
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experimental part
p. 631 - 635
(2012/07/03)
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- Poly(4-vinylpyridine) catalyzed chemoselective O-TMS protection of alcohols and phenols and N-Boc protection of amines
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Poly(4-vinylpyridine) (PVP) acts as an efficient and reusable catalyst for the selective and efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) and N-tert-butoxycarbonylation of amines with (Boc)2O. All reactions were performed under mild conditions in good to high yields. Iranian Chemical Society 2012.
- Shirini, Farhad,Khaligh, Nader Ghaffari
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p. 495 - 502
(2013/02/22)
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- ZnO nanorods as an efficient and heterogeneous catalyst for N-Boc protection of amines and amine derivatives
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An efficient ZnO nano catalyst, which was readily prepared from Zn(CH3CO2)2, 2H2O and PVP by a chemical solution approach has successfully catalyzed N-tertbutoxy carbonylation of amines. The ZnO nanorods were successful and gave promising results for highly active and chemoselective as well as easily recyclable catalyst for the NBoc protection reaction of a wide variety of amines. The catalyst could be easily recycled for five times without noticeable decrease in catalytic activity. The ZnO nanocatalyst was characterized with XRD and SEM.
- Nouria, Azita,Akbari, Jafar,Heydaric, Akbar,Nouri, Arezu
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experimental part
p. 38 - 42
(2012/05/04)
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- Protic ionic liquid [TMG][Ac] as an efficient, homogeneous and recyclable catalyst for Boc protection of amines
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An efficient and practical protocol for the chemoselective N-Boc protection of various structurally different aryl, aliphatic and heterocyclic amines was carried out with (Boc)2O using protic 1, 1, 3, 3-tetra-methylguanidinium acetate (10 mol%) as recyclable catalyst under solvent free condition at ambient temperature. No competitive side reactions (isocyanate, urea and N, N-di-Boc) were observed. α-Amino alcohols afforded the N-Boc-derivative without oxazolidinone formation.
- Akbari, Jafar,Heydari, Akbar,Ma'mani, Leila,Hassan Hosseini, Seyed
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experimental part
p. 544 - 547
(2010/11/05)
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- Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping
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Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopping. On the basis of the structure of lead molecule 6, fragment hopping effectively extracted the minimal pharmacophoric elements in the active site of nNOS for ligand hydrophobic and steric interactions and generated appropriate lipophilic fragments for lead optimization. More potent and selective inhibitors with better druglike properties were obtained within the design of 20 derivatives (compounds 7-26). Our structure - based inhibitor design for nNOS and SAR analysis reveal the robustness and efficiency of fragment hopping in lead discovery and structural optimization, which implicates a broad application of this approach to many other therapeutic targets for which known druglike small-molecule modulators are still limited.
- Ji, Haitao,Li, Huiying,Martásek, Pavel,Roman, Linda J.,Poulos, Thomas L.,Silverman, Richard B.
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experimental part
p. 779 - 797
(2009/12/07)
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- POTENT AND HIGHLY SELECTIVE HETEROAROMATIC INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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Peptidomimetic compounds as can inhibit neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as but not limited to stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease.
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Page/Page column 19; 21
(2008/06/13)
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- Hydrogen bond catalyzed chemoselective N-tert-butoxycarbonylation of amines
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A novel, chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butoxypyrocarbonate (Boc)2O is described that relies on selective carbonyl activation by hydrogen bond formation. This mild, acid- and metal-free process requires only catalytic amounts of thiourea as hydrogen bond donor.
- Khaksar, Samad,Heydari, Akbar,Tajbakhsh, Mahmood,Vahdat, Seyed Mohammad
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p. 3527 - 3529
(2008/09/21)
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- 1,1,1,3,3,3-Hexafluoroisopropanol: A recyclable organocatalyst for N-Boc protection of amines
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A simple and efficient protocol for the chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butyl dicarbonate using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent and catalyst is described. The catalyst can be readily separated from the reaction products and recovered for direct reuse. No competitive side reactions such as formation of isocyanate, urea, and N,N-di-Boc were observed. α-Amino alcohols afforded the N-Boc derivatives without oxazolidinone formation. Georg Thieme Verlag Stuttgart.
- Heydari, Akbar,Khaksar, Samad,Tajbakhsh, Mahmood
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experimental part
p. 3126 - 3130
(2009/04/06)
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- N-tert-Butoxycarbonylation of amines using H3PW12O40 as an efficient heterogeneous and recyclable catalyst
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The commercially available heteropoly acid H3PW12O40 (0.5 mol %) is a very efficient and environmentally benign catalyst for N-tert-butoxycarbonylation of amines (primary, secondary) with di-tert-butyl dicarbonate at room temperature in short reaction times (10 min). No competitive side products such as isocyanates, ureas, N,N-di-tert-butoxycarbonyls, O-Boc and oxazolidinones were observed. Chiral α-amino alcohols and esters afforded the corresponding N-Boc derivatives chemoselectively in excellent yields.
- Heydari, Akbar,Shiroodi, Roohollah Kazem,Hamadi, Hossein,Esfandyari, Maryam,Pourayoubi, Mehrdad
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p. 5865 - 5868
(2008/02/09)
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- DERIVATIVES OF 4-(2-AMINO-1-HYDROXIETHYL)PHENOL AS AGONISTS OF THE β2 ADRENERGIC RECEPTOR
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This invention is directed to compounds of formula (I): to pharmaceutical compositions comprising them; to combination products comprising them; and to their use in therapy.
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Page/Page column 57-58
(2008/06/13)
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- UROTENSIN II RECEPTOR ANTAGONISTS
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The invention is directed to Urotensin II antagonists. More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating Urotensin-II mediated disorders. Pharmaceutical and veterinary compositions and methods of treating cardiovascular disorders and various other disease states or conditions using compounds of the invention are also described.
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Page/Page column 189
(2010/11/28)
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- HETEROAROMATIC SELECTIVE INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.
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Page/Page column 17
(2008/06/13)
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- NOVEL OXABISPIDINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CARDIAC ARRHYTHMIAS
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There is provided compounds of formula I, wherein R1, R2, R4, R41 to R46, A, B and G have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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Page/Page column 83
(2008/06/13)
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- Imidazole and trifluoroethanol as efficient and mild reagents for destruction of excess di-tert-butyl dicarbonate [(BOC)2O]1
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Mild and efficient procedures employing inexpensive reagents (imidazole or trifluoroethanol) for the removal of excess (BOC)2O, usually used during NH or OH protection at room temperature, are described. The use of polymer-based DMAP with or without TFE was also found to be attractive.
- Basel,Hassner
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p. 550 - 552
(2007/10/03)
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- Pyrimidinone-1,3-oxathiolane derivatives with antiviral activity
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Compounds of formula (I) wherein Ra and Rb the same or different, are hydrogen atoms, acyl groups deriving from a lower carboxylic acid or chains of formula (a) useful as reverse transcriptase inhibitors antiviral activity are described.
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- Di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine revisited. Their reactions with amines and alcohols
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The reaction of BOC2O in the presence and absence of DMAP was examined with some amines, alcohols, diols, amino alcohols, and aminothiols. Often, unusual products were observed depending on the ratio of reagents, reaction time, polarity of solvent, pK(a) of alcohols, or type of amine (primary or secondary). In reactions of aliphatic alcohols with BOC2O/DMAP, we isolated for the first time carbonic-carbonic anhydride intermediates; this helps explain the formation of symmetrical carbonates in addition to the O-BOC products. In the case of secondary amines, we succeeded to isolate unstable carbamic-carbonic anhydride intermediates that in the presence of DMAP led to the final N-BOC product. The effect of N-methylimidazole in place of DMAP was also examined.
- Basel, Yochai,Hassner, Alfred
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p. 6368 - 6380
(2007/10/03)
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- New generation dopaminergic agents. 6. Structure-activity relationship studies of a series of 4-(aminoethoxy)indole and 4-(aminoethoxy)indolone derivatives based on the newly discovered 3-hydroxyphenoxyethylamine D2 template
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A series of 4-(aminoethoxy)indoles 7 and a related series of 4- (aminoethoxy)indolones 8 were synthesized and evaluated for their affinity for both the high- and low-affinity agonist states (D2(High) and D2(Low), respectively) of the dopamine (DA) D2 receptor. The 4-aminoethoxy derivatives (i.e., 7 and 8) were designed as bioisosteric analogues based on the phenol prototype 4. The indolones 8 were observed to have high affinity for the D2(High) receptor. Comparison of their previously reported chroman analogues with the more flexible 4-(aminoethoxy)indoles revealed the chroman analogues to be more potent, whereas little loss in D2(High) affinity was observed when comparing the 4-(aminoethoxy)indolones with their respective chroman analogues. Several regions of the phenoxyethylamine framework were modified and recognized as potential sites to modulate the level of intrinsic activity. A conformational analysis was performed and a putative bioactive conformation was proposed which fulfilled the D2 agonist pharmacophore criteria based on the McDermed model. Structure-activity relationships gained from these studies have aided in the synthesis of D2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo- and hyperdopaminergic activity, without the side effects associated with complete D2 agonism or antagonism.
- Mewshaw, Richard E.,Webb, Michael B.,Marquis, Karen L.,McGaughey, Georgia B.,Shi, Xiaojie,Wasik, Theodore,Scerni, Rosemary,Brennan, Julie A.,Andree, Terrance H.
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p. 2007 - 2020
(2007/10/03)
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- New generation dopaminergic agents. 2. Discovery of 3-OH-phenoxyethylamine and 3-OH-N1-phenylpiperazine dopaminergic templates
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Described in this report is a systematic study which led to the identification of two new dopamine D2 partial agonists (5 and 17). Phenols 5 and 17 represent prototypes of two new classes of D2 partial agonist as well as templates for the future design of novel dopaminergic agents.
- Mewshaw, Richard E.,Husbands, Morris,Gildersleeve, Elizabeth S.,Webb, Michael B.,Shi, Xiaojie,Mazandarani, Hossein,Cockett, Mark I.,Ochalski, Rafal,Brennan, Julie A.,Abou-Gharbia, Magid,Marquis, Karen,McGaughey, Georgia B.,Coupet, Joseph,Andree, Terrance H.
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p. 295 - 300
(2007/10/03)
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- Enantioselective synthesis of 1,2-, 1,3- and 1,4- aminoalcohols by the addition of dialkylzincs to 1,2-, 1,3- and 1,4- aminoaldehydes
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Chiral 1,3- and 1,4- aminoalcohols were prepared by the addition of functionalized dialkylzincs to 1,3-aliphatic and 1,4-unsaturated aminoaldehydes with good to excellent enantioselectivity. Syn- or anti-1,2- aminoalcohols are stereoselectively obtained by asymmetric addition of dialkylzincs to α-aminoaldehydes depending on the choice of the chiral catalyst. A chelate controlled addition is observed if less than stoichiometric amounts of Ti(Oi-Pr)4 are used.
- Lutz, Christian,Lutz, Volker,Knochel, Paul
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p. 6385 - 6402
(2007/10/03)
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- Synthesis and structure-activity relationships of 4-amino-5-chloro-2- ethoxybenzamides with six- and seven-membered heteroalicycles as potential gastroprokinetic agents
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A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b-f and 5-8 bearing six- and seven-membered heteroalicycles was prepared and evaluated for gastroprokinetic activity. Compounds 3b-e, derived by replacement of the morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2- ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally exhibited a potent gastric emptying activity. N-(4-Benzyl-3- morpholinyl)methylbenzamide (5a) and its analogues 5b-e had weaker activity. However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a. Benzamides 6a-e, having seven-membered heteroalicycles, showed fairly potent activity. Molecular superimpositions of 5a, 6a and 8 upon 3a using computer graphics suggested that the direction of the N-benzyl group greatly influences the gastric emptying activity, whereas the location of the alicyclic nitrogen is less critical.
- Morie,Kato,Harada,Yoshida,Fujiwara,Matsumoto
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p. 1137 - 1147
(2007/10/02)
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- Renin inhibitors having all retro-inverted peptide bonds
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Renin-inhibiting peptides of the formula STR1 in which X represents a group of the formula STR2 represents hydroxyl, alkoxy having up to 8 carbon atoms, benzyloxy or a group of the formula --NR4 R5, A, B, D and E are identical or different and in each case represent a direct bond, represent a radical of the formula STR3 in which Q1 denotes oxygen, sulphur or the methylene group represent a grouping of the formula STR4 m represents a number 0, 1 or 2, and L represents a group of the formula --CH2 NR2 R3 and physiologically acceptable salts thereof.
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