4136-95-2Relevant articles and documents
Synthesis, pH dependent, plasma and enzymatic stability of bergenin prodrugs for potential use against rheumatoid arthritis
Singh, Rohit,Kumar, Vikas,Bharate, Sonali S.,Vishwakarma, Ram A.
, p. 5513 - 5521 (2017/10/06)
Bergenin is a unique C-glycoside natural product possessing anti-inflammatory and anti-arthritic activity. It is hydrophilic molecule and stable under acidic conditions however is unstable at neutral-basic pH conditions. The rate of degradation is directly proportional to the increase in pH which might be one of the reasons for its low oral bioavailability. Thus, herein our objective was to improve its stability using prodrug strategy. Various ester and ether prodrugs were synthesized and studied for lipophilicity, chemical stability and enzymatic hydrolysis in plasma/esterase. The stability of synthesized prodrugs was evaluated in buffers at different pH, in biorelevant media such as SGF, SIF, rat plasma and in esterase enzyme. All prodrugs displayed significantly improved lipophilicity compared with bergenin, which was in accordance with the criteria of drug-like compounds. Acetyl ester 4a2 appeared to be the most promising prodrug as it remained stable at gastric/intestinal pH and was completely transformed to the parent compound bergenin in plasma as desired for an ideal prodrug. The data presented herein, will help in designing stable prodrugs of unstable molecules with desired physicochemical properties in structurally similar chemotypes.
SUBSTITUTED 1,2,5-OXADIAZOLE COMPOUNDS AND THEIR USE AS HERBICIDES
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Page/Page column 123, (2013/06/05)
The present invention relates to substituted 1,2,5-oxadiazole compounds of the formula I and the N-oxidesand salts thereof and to compositions comprising the same. The invention also relates to the use of the 1,2,5-oxadiazole compounds or of the compositions comprising such compounds for controlling unwanted vegetation. Furthermore,the invention relates to methods of applying such compounds. In formula I, the variables have the following meanigns R is e.g. hydrogen, cyano, nitro, halogen, C1-C6--alkyl, C3-C7-cycloalkyl, C3-C7- cycloalkyl-C1-C4-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl,C2-C6-haloalkynyl, C1-C4-alkoxy-C1-C4-alkyl,C1-C4-haloalkoxy-C1-C4-alkyl,O-Ra, Z-S(O)n-Rb, Z-C(=O)-Rc, Z-C(=O)-ORd, Z-C(=O)-NReRf, Z-NRgRh, Z-phenyl and Z-heterocyclyl etc; R1 ise.g. Z1-cyano, halogen, nitro, C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl,C1-C8-haloalkyl, C1-C8-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, Z1-C1-C4-alkoxy-C1-C4-alkoxy, C1-C4-alkylthio-C1-C4-alkyl, Z1-C1-C4-alkylthio-C1-C4-alkylthio, C2-C6-alkenyloxy, C2-C6-alkynyloxy, C1-C6-haloalkoxy, C1-C4-haloalkoxy-C1-C4-alkyl, Z1-C1-C4-haloalkoxy-C1-C4-alkoxy, Z1-S(O)k-R1b, Z1-phenoxy and Z1-heterocyclyloxy;R2,R3 are identical or different and e.g. hydrogen, halogen, Z2-OH, Z2-NO2,Z2-cyano,C1-C6-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, Z2-C3-C10-cycloalkyl, Z2-C3-C10-cycloalkoxy, C1-C8-haloalkyl, Z2-C1-C8-alkoxy, Z2-C1-C8-haloalkoxy, Z2-C1-C4-alkoxy-C1-C4-alkoxy, Z2-C1-C4-alkylthio-C1-C4-alkylthio, Z2-C2-C8-alkenyloxy, Z2-C2-C8-alkynyloxy, Z2-C1-C8-haloalkoxy, Z2-C2-C8-haloalkenyloxy, Z2-C2-C8-haloalkynyloxy, Z2-C1-C4- haloalkoxy-C1-C4-alkoxy, Z2-(tri-C1-C4-alkyl)silyl, Z2-S(O)k-R2b, Z2-C(=O)-R2c, Z2-C(=O)-OR2d, Z2-C(=O)-NR2eR2f, Z2-NR2gR2h, Z2a-phenyl and Z2a-heterocyclyl; R4 is selected from the group consisting of hydrogen, halogen, cyano, nitro, C1-C4-alkyl and C1-C4-haloalkyl; R5 is selected from the group consisting of hydrogen, halogen, C1-C4-alkyl and C1-C4-haloalkyl; provided that at least one of the radicals R4 and R5 is different from hydrogen; n is 0, 1 or 2; k is 0, 1 or 2.
JANUS KINASE INHIBITOR COMPOUNDS AND METHODS
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Page/Page column 100, (2010/12/29)
The invention provides compounds of Formula I, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, B, D, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and methods of use thereof
Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity
Laursen, Jane B.,De Visser, Peter C.,Nielsen, Henrik K.,Jensen, Knud J.,Nielsen, John
, p. 171 - 175 (2007/10/03)
An array of 12 new saphenamycin analogues modified at the benzoate moiety was synthesized on solid support. Synthesis commenced with a chemoselective anchoring of saphenic acid through the carboxyl group to a 2-chlorotrityl functionalized polystyrene resin. The secondary alcohol was acylated in parallel with a series of differently substituted benzoic acid derivatives. Treatment with TFA-CH2Cl2 (5:995) released the expected saphenamycin analogues into solution. These new analogues were purified, characterized and screened for antimicrobial activity against Bacillus subtilis and Proteus mirabilis. Eight analogues exhibited MIC values against B. subtilis ranging from 0.07 to 3.93 μg/mL, comparable to the activities of previously reported saphenamycin analogues.
3-aroylbenzylpyridazinone derivatives
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, (2008/06/13)
Compounds of formula I: STR1 where: R10 is a group represented by formula (A), (B), or (C): STR2 and the other substituents are as defined in the specification; and their pharmaceutically acceptable salts are inhibitors of prostaglandin G/H synthase and are anti-inflammatory and analgesic agents.
Benzylated 1,2,3-triazoles as anticoccidiostats
Bochis,Chabala,Harris,Peterson,Barash,Beattie,Brown,Graham,Waksmunski,Tischler,Joshua,Smith,Colwell,Wyvratt Jr.,Fisher,Tamas,Nicolich,Schleim,Wilks
, p. 2843 - 2852 (2007/10/02)
Substituted 5-amino-4-carbamoyl-1,2,3-triazoles 3a-w were prepared by two synthetic schemes and evaluated in vivo for anticoccidial activity. Both schemes proceeded by brominating appropriately substituted toluenes 4a-s,v to 5a-s,v. In Scheme I, the brominated benzyl analogues 5 were converted to the corresponding benzyl azides 6, which were treated with cyanoacetamide to yield 1-substituted-5-amino-4-carbamoyl-1,2,3-triazoles 3. In Scheme II, the benzyl halides 5 were employed to alkylate the sodium salt of 5-amino-4-carbamoyl-1,2,3-triazole (7). Preliminary screening data against Eimeria acervulina and E. tenella in chickens suggested structural requirements for maximizing activity. Further evaluation against a relatively resistant series of eight Eimeria field isolates revealed L-651,582 (3a) to be a highly effective coccidiostat. However, unacceptable tissue residues precluded further development. Mechanistic studies on this series of 5-amino-4-carbamoyl-1,2,3-triazoles and, in particular, on L-651,582 (3a) revealed that its mode of action does not involve inhibition of IMP dehydrogenase, but probably interferes with host cell calcium entry. In addition, L-651,582 has been found to have antiproliferative activity in several disease models and was recently reported to possess antimetastatic activity in a model of ovarian cancer progression.
