- The kinetic resolution of oxazinones by alcoholysis: access to orthogonally protected β-amino acids
-
The catalytic, alcoholytic kinetic resolution of oxazinones is reported. A novel, stereochemically dense cinchona alkaloid-based catalyst can facilitate the highly enantiodiscriminatory (Sup to 101) ring-opening of oxazinones equipped with electrophilic aryl units to generate orthogonally protected β-amino acids for the first time.
- Connon, Stephen J.,Cronin, Sarah A.
-
supporting information
p. 7348 - 7352
(2021/09/07)
-
- Trimethyl-substituted carbamate as a versatile self-immolative linker for fluorescence detection of enzyme reactions
-
Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.
- Inoue, Kazuya,Nakamura, Noriaki,Ojida, Akio,Uchinomiya, Shohei
-
supporting information
(2020/05/25)
-
- ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula I: or a pharmaceutical salt thereof, wherein p, s, A, R3 and Re are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Page/Page column 40
(2017/01/26)
-
- ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula I, or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, X1, X2, X3, X4, Y, Z, A, Het, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are as defined herein.. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis, muscular sclerosis and psoriasis.
- -
-
Page/Page column 69-70
(2017/01/26)
-
- HETEROARYL AMIDE SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula I: (I) or a pharmaceutical salt thereof, wherein m, n, p, q, Het, A, W, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Page/Page column 45; 46
(2017/07/06)
-
- ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, A, W, X1, X2, X3, X4, Y, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Paragraph 1210; 1211
(2016/07/05)
-
- HETEROARYLALKYLENE ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula (I): or a pharmaceutical salt thereof, wherein m, n, p, q, Het, A, W, R1, R2, R3, R4, R5, R6, R7, R8, R and R10are as defined herein are modulators of retinoid-receptor related orphan receptor RORc (RORy). Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Page/Page column 42
(2016/07/05)
-
- Synthesis of Substituted Quinolizidines via a Gold-Catalyzed Double Cyclization Cascade
-
A novel synthesis of quinolizidines by a cationic gold-catalyzed double cyclization cascade has been developed. The reaction was initiated by the gold-catalyzed 6-exo-dig cyclization of ynamides, which was followed by a second cyclization of an enamide intermediate to provide the corresponding quinolizidine derivatives. The utility of this reaction was demonstrated by application to the synthesis of multi-substituted quinolizidines and by the total synthesis of a quinolizidine alkaloid, (±)-lupinine.
- Nonaka, Shiori,Sugimoto, Kenji,Ueda, Hirofumi,Tokuyama, Hidetoshi
-
supporting information
p. 380 - 385
(2016/02/12)
-
- ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, A, W, X1, X2, X3, X4, Y, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Paragraph 1201; 1202
(2015/07/22)
-
- IOP-lowering effect of isoquinoline-5-sulfonamide compounds in ocular normotensive monkeys
-
Rho-associated coiled coil-formed protein kinase (ROCK) inhibitors are under development as a new class of antiglaucoma agents. Based on the potent ROCK inhibitor H-1152, previously developed by us, we explored the possibility of related compounds as anti
- Sumi, Kengo,Inoue, Yoshihiro,Nishio, Masahiro,Naito, Yasuhito,Hosoya, Takamitsu,Suzuki, Masaaki,Hidaka, Hiroyoshi
-
p. 831 - 834
(2014/02/14)
-
- ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein m, n, p, q, r, A, W, X1, X2, X3, X4, Y, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Page/Page column 96
(2014/02/15)
-
- ARYL SULTAM DERIVATIVES AS RORc MODULATORS
-
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, p, q, Ar, A, W, X1, X2, X3, X4, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.
- -
-
Page/Page column 42
(2015/01/07)
-
- Synthesis of chiral non-racemic intermediates and Arg-Gly-Asp mimetics by CaLB-catalyzed resolution
-
The reactivity of both the ester and amine functions present in β-amino esters was tested in order to obtain the synthesis of enantiopure αvβ3 and α5β1 integrin ligands. CaLB successfully catalyzed both the enantioselective transesterification and the N-acylation of racemic β-amino esters, allowing the isolation of intermediates for the preparation of Arg-Gly-Asp (RGD) mimetic compounds. In particular, a CaLB-catalyzed amidation reaction with unprotected p-aminobenzylamine reduced the number of synthetic steps, thus avoiding protection and deprotection of the intermediate compounds. Following this procedure, RGD mimetics were isolated with high yields and enantiomeric purities.
- Cardillo, Giuliana,Gennari, Arianna,Gentilucci, Luca,Mosconi, Elisa,Tolomelli, Alessandra,Troisi, Stefano
-
experimental part
p. 96 - 102
(2010/04/06)
-
- Design and synthesis of C5 methylated L-arginine analogues as active site probes for nitric oxide synthase
-
The role of nitric oxide (NO) as a biological signaling molecule is well established. NO is produced by the nitric oxide synthases (NOSs, EC 1.14.13.39), a class of heme proteins capable of converting L-arginine to NO and L-citrulline. Despite the large body of knowledge associated with the NOSs, mechanistic details relating to the unique oxidative chemistry performed by these enzymes remain to be fully elucidated. Furthermore, a number of disease states are associated with either the over- or underproduction of NO, making the NOS pathway an attractive target for the development of therapeutics. For these reasons, molecular tools capable of providing mechanistic insights into the production of NO and/or the inhibition of the NOSs remain of interest. We report here the stereospecific synthesis and testing of a number of new L-arginine analogues bearing a minimal substitution, methylation at position 5 of the amino acid side chain (such analogues have not been previously reported). The synthetic approach employed a modified photolysis procedure whereby irradiation of the appropriate diacylperoxide precursors at 254 nm gave access to the required unnatural amino acids in good yields. A heme domain construct of the inducible NOS isoform (iNOSheme) was used to assess the binding of each compound to the enzyme active site. The compounds were also investigated as either inhibitors of, or alternate substrates for, the inducible NOS isoform. The results obtained provide new insight into the steric and stereochemical tolerance of the enzyme active site. These findings also further support the role of a conserved active site water molecule previously proposed to be necessary for NOS catalysis.
- Martin, Nathaniel I.,Woodward, Joshua J.,Winter, Michael B.,Beeson, William T.,Marletta, Michael A.
-
p. 12563 - 12570
(2008/09/18)
-
- CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS
-
Compounds of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), A1 is a cyclic group, and B is a cyclic group which is attached to the heterocyclic ring directly or through a methylene group.
- -
-
Page/Page column 38
(2008/06/13)
-
- PYRAZOLE DERIVATIVES, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
-
The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C1-6 alkyl group etc.; R2 represents H, a halogen atom, OH, an optionally substituted C1-6 alkyl group etc.; X represents a single bond, O or S; Y represents an optionally substituted C1-6 alkylene group etc.; Z represents -RB, -CORC etc. in which RB represents an optionally substituted C1-6 alkyl group etc.; and RC represents an optionally substituted C1-6 alkyl group etc.,; R4 represents H, an optionally substituted C1-6 alkyl group etc.; and R3, R5 and R6 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, impaired glucose tolerance, impaired fasting glycemia, diabetic complications or obesity, and a disease associated with the increase of blood galactose level such as galactosemia, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.
- -
-
Page/Page column 93
(2010/02/12)
-
- New methodology for the synthesis of unsaturated 8-, 9- and 10-membered lactams
-
Unsaturated 8-, 9- and 10-membered medium ring lactams 1 (n = 1, 2, 3) have been prepared in good yield by the Claisen rearrangement of the vinyl-substituted precursors 3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
- Evans, P. Andrew,Holmes, Andrew B.,McGeary, Ross P.,Nadin, Alan,Russell, Keith,O'Hanlon, Peter J.,Pearson, Neil D.
-
p. 123 - 138
(2007/10/03)
-
- Metal-Assisted Aldol Condensation of Chiral 6-Methyl Perihydropyrimidin-4-ones
-
The synthesis of 6-methyl perihydropyrimidin-4-ones (1'S,6R)-3a and (1'S,6S)-3b is reported starting from rac-3-aminobutanoic acid.The aldol condensation of various metal enolates of 3a and 3b with benzaldehyde and acetaldehyde is reported.All reactions a
- Amoroso, Rosa,Cardillo, Giuliana,Mobbili, Giovanna,Tomasini, Claudia
-
p. 2241 - 2254
(2007/10/02)
-
- 194. Diastereoselecktive Alkylation of 3-Aminobutanoic Acid in the 2-Position
-
The enantiomerically pure 3-aminobutanoic acids (R)- and (S)-6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-methyl 3-(benzoylamino)butanoate ((S)-3) is also available by enzymatic kinetic resolution with pig-liver esterase.The N-benzoyl- and N-benzyloxycarbonyl derivatives rac-3, 8,and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2).The configuration of three of the products is assigned (Schemes 4-6), and in four cases, the free α-substituted β-amino acid is prepared by acidic hydrolysis (see Table 3).It is shown that the doubly lithiated β-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.
- Estermann, Heinrich,Seebach, Dieter
-
p. 1824 - 1840
(2007/10/02)
-