- STUDIES DIRECTED TOWARDS THE TOTAL SYNTHESIS OF DICYCLOPENTACYCLOOCTANE TERPENOIDS.
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A general strategy for the synthesis of dicyclopentacyclooctane terpenoids is reported.Compound 1 was synthesized from 3-methoxycarbonyl-2-cyclopentenone; its photocycloaddition led to four diastereoisomeric photoadducts whose structure were determined by X-ray analysis, 1H-NMR data and chemical transformations.
- De Gregori, A.,Jommi, G.,Sisti, M.,Gariboldi, P.,Merati, F.
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- CYTOTOXIC BIS-BENZODIAZEPINE DERIVATIVES AND CONJUGATES THEREOF WITH CELL-BINDING AGENTS FOR INHIBITING ABNORMAL CELL GROWTH OR FOR TREATING PROLIFERATIVE DISEASES
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The invention relates to benzodiazepine derivatives with antiproliferative activity and more specifically to benzodiazepine compounds of formulae (I), (II), (TI) and (T2). The invention also provides conjugates of the benzodiazepine compounds linked to a
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Paragraph 00311
(2020/10/20)
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- MUSCARINIC ACETYLCHOLINE M1 RECEPTOR ANTAGONISTS
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Provided herein are compounds which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.
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Paragraph 00353
(2020/01/08)
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- An improved synthesis of the selective EP4 receptor agonist ONO-4819
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(Chemical Equation Presented) An improved synthesis of the highly selective EP4-receptor agonist ONO-4819 has been developed. The previous synthesis suffered from several drawbacks, in which a critical one is the difficulty in the removal of byproducts leading to unsatisfactory quality of the active pharmaceutical ingredient (API). Furthermore, on stereoselective reduction of an enone intermediate by binaphthol-modified lithium aluminum hydride, low concentration of the reaction conditions and tedious purification procedures to remove excess binaphthol were critical issues for the manufacturing process of the API. In the improved process,we have developed improved conditions using γ-thiobutyrolactone as sulfur source instead of potassium thioacetate to introduce the sulfur-containing C4 side chain without formation of byproducts. For stereoselective synthesis of the chiral alcohol, (-)-DIP-chloride reduction is found to be the best method, which can improve not only the enantioselectivity but also the workload for removing the chiral modifier in a purification process. Furthermore, benzoyl and tert-butyldimethylsilyl groups as protecting groups for hydroxyl functions were used for precise process controls of all intermediates. By changing these protecting groups, the purity of ONO-4819 was strictly controlled through crystalline intermediates. Thus, an improved robust process for ONO-4819 with a high chemical purity was developed. 2009 American Chemical Society.
- Ohta, Chisa,Kuwabe, Shin-Itsu,Shiraishi, Tai,Shinohara, Ikuo,Araki, Hiroshi,Sakuyama, Shigeru,Makihara, Takayuki,Kawanaka, Yasufumi,Ohuchida, Shuichi,Takuya, Seko
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experimental part
p. 8298 - 8308
(2010/02/17)
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- Solid-phase synthesis of thermolytic DNA oligonucleotides functionalized with a single 4-hydroxy-1-butyl or 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group
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(Chemical Equation Presented) Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).
- Grajkowski, Andrzej,Ausin, Cristina,Kauffman, Jon S.,Snyder, John,Hess, Sonja,Lloyd, John R.,Beaucage, Serge L.
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p. 805 - 815
(2007/10/03)
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- BISPHENYL COMPOUNDS USEFUL AS VITAMIN D3 RECEPTOR AGONISTS
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The present invention discloses bisphenyl compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, X, Y, W are defined herein after. These compounds are useful as pharmaceuticals.
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Page/Page column 337
(2010/02/14)
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- Design, Synthesis, and 5-Lipoxygenase-Inhibiting Properties of 1-Thio-Substiuted Butadienes
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The synthesis of novel 1-thio-substituted butadienes, designed as mechanism-based 5-lipoxygenase inhibitors, is described.The structure of these compounds closely resembles a proposed high-energy intermediate during the lipoxygenation of arachidonic acid.They demonstrate 5-lipoxygenase inhibition in vitro and in vivo.The most potent compound is 15a with an IC50 of μM in vitro.LTC4 release was inhibited by 80percent after intraperitoneal administration of 15c at a dose of 2 mg/kg.
- Hanko, Rudolf,Hammond, Michael D.,Fruchtmann, Romanis,Pfitzner, Joerg,Place, Graham A.
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p. 1163 - 1170
(2007/10/02)
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