- Visible-Light-Induced Cycloaddition of α-Ketoacylsilanes with Imines: Facile Access to β-Lactams
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We report the synthesis of β-lactams from α-ketoacylsilanes and imines, which proceeds via a formal [2+2] photochemical cycloaddition with in situ generation of siloxyketene. This mild and operationally simple reaction proceeds in an atom-economic fashion with broad substrate scope, including aldimines, ketimines, hydrazones, and fused nitrogen heterocycles, affording a variety of important β-lactams with satisfactory diastereoselectivities in most cases. This reaction also features good functional-group tolerance, facile scalability and product diversification. Experimental and computational studies suggest that α-ketoacylsilanes can serve as photochemical precursors by engaging in a 1,3 silicon shift to the distal carbonyl group.
- Ye, Jian-Heng,Bellotti, Peter,Paulisch, Tiffany O.,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 13671 - 13676
(2021/05/11)
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- Dibenzo[b,e]aza-6,11-diketotriazole compound as well as preparation method and application thereof
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The invention provides a dibenzo[b,e]aza-6,11-diketotriazole compound and a preparation method thereof, belongs to the technical field of medicines, and specifically relates to a 5-((1-(R-phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5H-dibenzo[b,e]aze-6,11-diketone anti-tumor compound as well as a preparation method and application thereof. The compound prepared by the invention has a function of inhibiting tumor activity and has excellent application prospect in the field of design, research and development of anti-tumor drugs; in addition, the preparation method is simple and easy to industrialize.
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Paragraph 0060; 0066; 0067
(2019/09/05)
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- Mechanistic study of a complementary reaction system that easily affords quinazoline and perimidine derivatives
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A new reaction between 2-aminobenzophenone and thiourea in dimethyl sulfoxide (DMSO) has been developed that primarily affords 4-phenylquinazoline as a single product. This reaction is also applicable, in general, to the reactions between thiourea and conformation-restricted β-amino ketones, such as 1-aminoanthracene-9,10-dione and 1-amino-9H-fluoren-9-one, to prepare perimidine derivatives. Experimental data is consistent with our computational study on the thermal decomposition of thiourea to form hydrogen sulfide and carbodiimide. This reaction involves a coupling between 2-aminobenzophenone and carbodiimide generated in situ from thiourea to form 4-phenylquinazolin-2(1H)-imine intermediate, and the generation of sulfur-containing reducing agent from hydrogen sulfide and DMSO, which reduces 4-phenylquinazolin-2(1H)-imine to 4-phenyl-1,2-dihydroquinazolin-2-amine. Elimination of ammonia from the latter yields 4-phenylquinazoline.
- Wang, Zerong Daniel,Eilander, Joshua,Yoshida, Motoko,Wang, Tianzhi
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supporting information
p. 7664 - 7674
(2015/04/22)
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- Synthesis and SAR of selective small molecule neuropeptide y Y2 receptor antagonists
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Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM 9552) with IC50 values of 19 nM and 12 nM respectively.
- Mittapalli, Gopi Kumar,Vellucci, Danielle,Yang, Jun,Toussaint, Marion,Brothers, Shaun P.,Wahlestedt, Claes,Roberts, Edward
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scheme or table
p. 3916 - 3920
(2012/07/03)
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- Application of the guanidine-acylguanidine bioisosteric approach to argininamide-type NPY Y2 receptor antagonists
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Strongly basic groups such as guanidine moieties are crucial structural elements, but they compromise the drug-likeness of numerous biologically active compounds, including ligands of G-protein-coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide-type neuropeptideY (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG-acylated argininamides were obtained by guanidinylation with tailor-made mono-Boc-protected N-acyl-S-methylisothioureas. The compounds were investigated for Y2R antagonism (calcium assays), Y2R affinity, and NPY receptor subtype selectivity (flow cytometric binding assays). Most of the NG-substituted (S)-argininamides showed Y2R antagonistic activities and binding affinities similar to those of the parent compound, whereas NG-acylated or -carbamoylated analogues with a terminal amine were superior (Y2R: Ki and KB values in the low nanomolar range). This demonstrates that the basicity of the compounds, although 4-5 orders of magnitude lower than that of guanidines, is sufficient to form key interactions with acidic amino acids of the Y2R. The acylguanidines bind with high affinity and selectivity to Y2R over the Y1, Y4, and Y5 receptors. As derivatization of the amino group is tolerated, these compounds can be considered building blocks for the preparation of versatile fluorescent and radiolabeled pharmacological tools for invitro studies of the Y2R. The results support the concept of bioisosteric guanidine-acylguanidine exchange as a broadly applicable approach to retain pharmacological activity despite decreased basicity.
- Pluym, Nikola,Brennauer, Albert,Keller, Max,Ziemek, Ralf,Pop, Nathalie,Bernhardt, Guenther,Buschauer, Armin
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scheme or table
p. 1727 - 1738
(2012/01/14)
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- Iron-catalyzed C-H and C-C bond cleavage: A direct approach to amides from simple hydrocarbons
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Something functional: The title reaction proceeds in the presence of azide and water to deliver amides in high yields, and it can be used in a ring-expansion strategy to generate lactams. A mechanism is proposed based on experimental results. This reaction offers a new approach to functionalizing simple and readily available hydrocarbons. DDQ=2,3-dichloro-5,6-dicyano-1,4- benzoquinone. Copyright
- Qin, Chong,Zhou, Wang,Chen, Feng,Ou, Yang,Jiao, Ning
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supporting information; experimental part
p. 12595 - 12599
(2012/01/15)
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- NON-STEROIDAL COMPOUNDS USEFUL AS GLUCOCORTICOID RECEPTOR MODULATORS
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This invention relates to novel amino acid derivatives of formula (I) wherein the R groups have the following meanings: -R1 is -H or -(1-4C)alkyl; -R2 is -C(O)R15 or -S(O)2R15; -R3 is -H, -(1-4C)alkyl or -OR16; -R4 is -H, -(1-4C)alkyl or -OR16; -R6 is -H or -C(R16)NOR16; -R7 is -H, -halogen, -cyano; -(1-6C)alkyl, -(2-6C)alkenyl or -(2-6C)alkynyl, all optionally substituted with -amino, -hydroxyl or -halogen; -R8 is -H, -cyano, -halogen, -nitro; -(1-6C)alkyl, -(2-6C)alkenyl, -(2-6C)alkynyl or -O(l-6C)alkyl, all optionally substituted with -amino, -hydroxyl or -halogen; -(hetero)aryl, optionally substituted with -cyano, -halogen, -(1-4C)alkyl, -(1-4C)alkoxy, -(l-4C)alkoxy(l- 4C)alkyl or -(hetero)aryl; -C(R16)NOR16; -C(O)N(R17)2; -C(O)R18, -C(O)OR19, -NHC(O)R20, or -NHS(O)2R21; -R9 is -H, -halogen, -cyano, or -(1-4C)alkyl, optionally substituted with -halogen; -R10 is -H or -(1-4C)alkyl; -R11 is -H; -R12 is -H, -cyano or - (1-4C)alkyl; -R13 is -H, -(1-4C)alkyl, -halogen or -formyl; -R14 is -H, -halogen, -cyano, -(1-4C)a!kyl or -(hetero)aryl; or a pharmaceutically acceptable salt thereof. The compounds of this invention are highly specific for the glucocorticoid receptor and may be used for treating inflammatory diseases.
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Page/Page column 13
(2008/06/13)
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- DIPEPTIDYL PEPTIDASE-IV INHIBITORS
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The present invention relates generally to pyrrolidine and thiazolidine DPP-IV inhibitor compounds. The present invention also provides synthetic methods for preparation of such compounds, methods of inhibiting DPP-IV using such compounds and pharmaceutical formulations containing them for treatment of DPP-IV mediated diseases, in particular, Type-2 diabetes.
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Page/Page column 112
(2008/06/13)
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- Studies in large ring compounds: Synthesis of some new morphanthrindines and diazocines
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A novel method for the synthesis of 2 or 3-substituted 5,6-dihydro-6,11-dioxo-morphanthridines (2) involving the cyclisation of anilinic acid (1) with PPA/AcOH has been developed. A new heterocyclic system, 2 or 3-Substituted 5,6,11,12-tetrahydrodibenzo[b, f] [1,4]diazocine-6,11-diones(4) has been synthesized with excellent yields.
- Pawar,Bhusare,Pawar,Bhawal
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p. 1929 - 1936
(2007/10/03)
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- Synthesis and SAR of N-substituted dibenzazepinone derivatives as novel potent and selective αVβ3 antagonists
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Synthesis and SARs of new integrin αVβ3 antagonists based on an N-substituted dibenzazepinone scaffold are described. Variation of spacer and guanidine mimetic led to potent compounds exhibiting an IC50 towards αVβ3 in the nanomolar range, high selectivity versus integrin αIIbβ3 and efficacy in functional cellular assays.
- Kling, Andreas,Backfisch, Gisela,Delzer, Juergen,Geneste, Herve,Graef, Claudia,Holzenkamp, Uta,Hornberger, Wilfried,Lange, Udo E.W,Lauterbach, Arnulf,Mack, Helmut,Seitz, Werner,Subkowski, Thomas
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p. 441 - 446
(2007/10/03)
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- Morphanthridines: Part II - Syntheses of 5,6-Dihydro-6,11-dioxomorphanthridine, 1 (or 2)-Substituted 6,11-Dioxo-5,6-dihydromorphanthridines and 7H-12,13-Dihydro-7,12-dioxobenzonaphthazepine
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A novel method for the synthesis of substituted 5,6-dihydro-6,11-dioxomorphanthridines (IV) involving the cyclization of anilic acids (III) with PPA has been developed.A new heterocyclic system, 7H-12,13-dihydro-7,12-dioxobenzonaphthazepine (VII), has also been synthesized.
- Sinha, Ashok Kumar,Nizamuddin, S.
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