- A kind of IDO inhibitor and use thereof
-
The embodiment of the invention provides general formula (I) compound or its pharmaceutically acceptable salts, stereoisomers, a tautomeric form each other, polymorphs, solvate, prodrug, metabolite or isotope derivatives, wherein the substituents R1
- -
-
Paragraph 0731-0735
(2019/07/11)
-
- Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl-Functionalized Tetrazines
-
The inverse-electron-demand Diels–Alder/pyridazine elimination tandem reaction, in which the allylic substituent on trans-cyclooctene is eliminated following reaction with tetrazines, is gaining interest as a versatile bioorthogonal process. One potential shortcoming of such currently used reactions is their propensity to proceed faster and more efficiently at lower pH, a feature caused by the nature of the tetrazines used. Here, we present aminoethyl-substituted tetrazines as the first pH-independent reagents showing invariably fast elimination kinetics at all biologically relevant pH values.
- Sarris, Alexi J. C.,Hansen, Thomas,de Geus, Mark A. R.,Maurits, Elmer,Doelman, Ward,Overkleeft, Herman S.,Codée, Jeroen D. C.,Filippov, Dmitri V.,van Kasteren, Sander I.
-
supporting information
p. 18075 - 18081
(2018/11/23)
-
- Synthesis of novel amide and urea derivatives of thiazol-2-ethylamines and their activity against Trypanosoma brucei rhodesiense
-
2-(2-Benzamido)ethyl-4-phenylthiazole (1) was one of 1035 molecules (grouped into 115 distinct scaffolds) found to be inhibitory to Trypanosoma brucei, the pathogen causing human African trypanosomiasis, at concentrations below 3.6 μM and non-toxic to mammalian (Huh7) cells in a phenotypic high-throughput screen of a 700,000 compound library performed by the Genomics Institute of the Novartis Research Foundation (GNF). Compound 1 and 72 analogues were synthesized in this lab by one of two general pathways. These plus 10 commercially available analogues were tested against T. brucei rhodesiense STIB900 and L6 rat myoblast cells (for cytotoxicity) in vitro. Forty-four derivatives were more potent than 1, including eight with IC50 values below 100 nM. The most potent and most selective for the parasite was the urea analogue 2-(2-piperidin-1-ylamido)ethyl-4-(3-fluorophenyl)thiazole (70, IC50 = 9 nM, SI > 18,000). None of 33 compounds tested were able to cure mice infected with the parasite; however, seven compounds caused temporary reductions of parasitemia (≥97%) but with subsequent relapses. The lack of in vivo efficacy was at least partially due to their poor metabolic stability, as demonstrated by the short half-lives of 15 analogues against mouse and human liver microsomes.
- Patrick, Donald A.,Wenzler, Tanja,Yang, Sihyung,Weiser, Patrick T.,Wang, Michael Zhuo,Brun, Reto,Tidwell, Richard R.
-
p. 2451 - 2465
(2016/05/19)
-
- Synthesis and structural characterization of monomeric and dimeric peptide nucleic acids prepared by using microwave-promoted multicomponent reactions
-
A solution phase synthesis of peptide nucleic acid monomers and dimers was developed by using microwave-promoted Ugi multicomponent reactions. A mixture of a functionalized amine, a carboxymethyl nucleobase, paraformaldehyde and an isocyanide as building blocks generates PNA monomers which are then partially deprotected and used in a second Ugi 4CC reaction, leading to PNA dimers. Conformational rotamers were identified by using NMR and MD simulations.
- Ovadia, Reuben,Lebrun, Aurélien,Barvik, Ivan,Vasseur, Jean-Jacques,Baraguey, Carine,Alvarez, Karine
-
p. 11052 - 11071
(2015/11/25)
-
- A multifaceted secondary structure mimic based on piperidine-piperidinones
-
Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.
- Xin, Dongyue,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
-
supporting information
p. 3594 - 3598
(2014/04/17)
-
- New thiadiazole derivatives
-
The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful in the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
- -
-
Page/Page column 49
(2011/04/25)
-
- NEW THIADIAZOLE DERIVATIVES
-
The present invention relates to thiadiazole derivatives of formula (I), to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent agonists of S1P1 receptors and thus, they are useful In the treatment, prevention or suppression of diseases and disorders known to be susceptible to improvement by sphingosine-1-phosphate receptors agonists (S1P1), such as autoimmune diseases, chronic immune and inflammatory diseases, transplant rejection, malignant neoplastic diseases, angiogenic-related disorders, pain, neurological diseases, viral and infectious diseases.
- -
-
Page/Page column 71
(2011/04/24)
-
- Synthesis of (2R,3R,4S)-N-Boc-2,4-diarylpyrrolidine-3-carboxamides
-
A synthesis of (2R,3R,4S)-N-boc-2,4-diarylpyrrolidine-3-carboxylic amides (i-vii) via HATU, BOP and Mukaiyama mediated coupling of (2R,3R,4S)-1-(tert- butoxycarbonyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl) pyrrolidine-3-carboxylic acid (13) with amine (a1-g1) has been developed. Under HATU coupling conditions, the products were achieved in good yields comparatively than BOP and Mukaiyama reagent. The structures of compounds i-vii were elucidated on the basis of spectral and chemical studies.
- Jayachandra Reddy,Somasekhara Reddy
-
experimental part
p. 5165 - 5174
(2012/07/28)
-
- FUSED BICYCLIC COMPOUNDS AS INHIBITORS FOR PI3 KINASE
-
The invention relates to compounds of formula (I) for the regulation of phosphoinositides 3-kinases activity and related diseases.
- -
-
Page/Page column 111
(2010/09/18)
-
- IBX/TBAB-mediated oxidation of primary amines to nitriles
-
The combination of o-iodoxybenzoic acid (IBX) and tetrabutylammonium bromide (TBAB) efficiently oxidizes primary amines to the corresponding nitriles in good to excellent yield under mild conditions. The reaction is racemization-free when applied to a chiral lysine derivative. Georg Thieme Verlag Stuttgart.
- Drouet, Fleur,Fontaine, Patrice,Masson, Geraldine,Zhu, Jieping
-
experimental part
p. 1370 - 1374
(2010/01/13)
-
- BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS KINASE INHIBITORS
-
Phosphatidylinositol (PI) 3-kinase inhibitor compounds, their pharmaceutically acceptable salts, and prodrugs thereof; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.
- -
-
Page/Page column 80
(2009/03/07)
-
- 2-(AMINO-SUBSTITUTED)-4-ARYL PYRAMIDINES AND RELATED COMPOUNDS USEFUL FOR TREATING INFLAMMATORY DISEASES
-
A heterocyclic inhibitor having the formula (I), with the variables defined herein, which is useful for treating inflammatory and other physiological disorders in which PKC-theta isoform plays a role.
- -
-
Page/Page column 130
(2008/06/13)
-
- 3,3,3-TRIFLUORO-2-MERCAPTOMETHYL-N-TETRAZOLYL SUBSTITUTED PROPANAMIDES AND METHOD OF USING SAME
-
Compounds of the formula STR1 wherein Y can be tetrazolyl are disclosed. These compounds are useful as cardiovascular agents.
- -
-
-
- THIAZOLE DERIVATIVES ACTIVE ON THE CHOLINERGIC SYSTEM, PROCESS FOR OBTENTION AND PHARMACEUTICAL COMPOSITIONS
-
The invention relates to thiazole derivatives corresponding to the general formula: STR1 in which: R 1 and R 2 each independently represent hydrogen; a C 1-C 4 alkyl group; a phenyl group or a phenyl group monosubstituted or polysubstituted by a halogen a
- -
-
-
- Dithio and thiono esters, LVII: Synthesis of dithio and thiono esters of N-protected β- and γ-amino acids
-
The N-protected β-aminonitriles 1 were transformed into the imidoester or thiolimidoester hydrochlorides 2 or 3 according to Pinner and sulfhydrolyzed with H2S to give the N-protected β-amino thiono esters 4 or dithio esters 5. Alkylation of th
- Brutsche,Hartke
-
p. 271 - 276
(2007/10/02)
-
- A Convenient and General Method for the Preparation of tert-Butoxycarbonylaminoalkanenitriles and Their Conversion to Mono-tert-butoxycarbonylalkanediamines
-
A new method is described for the synthesis of tert-butoxycarbonylaminoalkanenitriles 3 by dehydration of the corresponding carboxamides 2 (prepared in two steps from aminoalkanoic acids) in the presence of trifluoroacetic anhydride and triethylamine.N-Boc-aminoalkanenitriles 3 are easily converted to mono-N-Boc-alkanediamines 4 under mild conditions avoiding the cleavage of the N-protective group.The monoprotected alkanediamines 4 are useful tools in affinity chromatography.
- Houssin, Raymond,Bernier, Jean-Luc,Henichart, Jean-Pierre
-
p. 259 - 261
(2007/10/02)
-
- Acylation of Dibasic Compounds Containing Amino Amidine and Aminoguanidine Functions
-
The site of acylation in difunctional compounds containing an amine and either an amidine or guanidine can be determined from the ultraviolet absorption spectrum of the acylated product.If the amidine or guanidine has been acylated, the product possesses a chromophore that is pH dependent, whereas if an amide was formed, the chromophore is independent of pH.
- Barker, Peter L.,Gendler, Paul L.,Rapoport, Henry
-
p. 2455 - 2465
(2007/10/02)
-
