- TRIAZACYCLODODECANSULFONAMIDE ("TCD")-BASED PROTEIN SECRETION INHIBITORS
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Provided herein are triazacyclododecansulfonamide ("TCD")-based protein secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same. For example, provided herein are compounds of Formula (I) and pharmaceutically acceptable salts and compositions including the same. The compounds disclosed herein may be used, for example, in the treatment of diseases including inflammation and/or cancer.
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Paragraph 00290
(2019/10/04)
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- Synthesis of novel optical isomers of α-methylpolyamines
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Earlier unknown (R)- and (S)-α-methylspermidine, (R)- and (S)-α-methylspermine, (R,R)-, (S,S)-, and (R,S)-α,ω-dimethylspermine were synthesized in gram scale from readily available (R)- and (S)-2-aminopropanols in high overall yields.
- Grigorenko, Nikolay A.,Khomutov, Alex R.,Kein?nen, Tuomo A.,J?rvinen, Aki,Alhonen, Leena,J?nne, Juhani,Veps?l?inen, Jouko
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p. 2257 - 2262
(2007/10/03)
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- POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY
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The present invention is to provide a novel compound (I), having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. Compound (I) wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
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Page/Page column 122; 164
(2010/11/24)
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- α-methyl polyamines: Efficient synthesis and tolerance studies in vivo and in vitro. First evidence for dormant stereospecificity of polyamine oxidase
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Efficient syntheses of metabolically stable α-methylspermidine 1, α-methylspermine 2, and bis-α,α-methylated spermine 3 starting from ethyl 3-aminobutyrate are described. The biological tolerance for these compounds was tested in wild-type mice and transgenic mice carrying the metallothionein promoter-driven spermidine/spermine N1- acetyltransferase gene (MT-SSAT). The efficient substitution of natural polyamines by their derivatives was confirmed in vivo with the rats harboring the same MT-SSAT transgene and in vitro with the immortalized fibroblasts derived from these animals. Enantiomers of previously unknown 1-amino-8-acetamido-5-azanonane dihydrochloride 4 were synthesized starting from enantiomerically pure (R)- and (S)-alaninols. The studies with recombinant human polyamine oxidase (PAO) showed that PAO (usually splits achiral substrates) strongly favors the (R)-isomer of 4 that demonstrates for the first time that the enzyme has hidden potency for stereospecificity.
- J?rvinen, Aki J.,Cerrada-Gimenez, Marc,Grigorenko, Nikolay A.,Khomutov, Alex R.,Veps?l?inen, Jouko J.,Sinervirta, Riitta M.,Kein?nen, Tuomo A.,Alhonen, Leena I.,J?nne, Juhani E.
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p. 399 - 406
(2007/10/03)
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- Synthesis of (R)- and (S)-isomers of 1-methylspermidine
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Previously unknown (R)- and (S)-isomers of 1,8-diamino-5-azanonane were prepared starting from (R)- and (S)-2-aminopropanols.
- Grigorenko, Nikolay A.,Vepsalainen, Jouko,Jarvinen, Aki,Keinanen, Tuomo,Alhonen, Leena,Janne, Juhani,Khomutov, Alex R.
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p. 142 - 143
(2007/10/03)
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- Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety
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A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine 'D' region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene α to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60c which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.
- Lebreton, Luc,Jost, Eric,Carboni, Bertrand,Annat, Jocelyne,Vaultier, Michel,Dutartre, Patrick,Renaut, Patrice
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p. 4749 - 4763
(2007/10/03)
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- 15-deoxyspergualin analogs, their method of preparation and their use in therapeutics
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The present invention relates, by way of novel industrial products, to compounds which are structurally related to 15-deoxyspergualin and which have the formula STR1 in which: A is a single bond, a group --CH2 --, a group --CH2 O--, a group --CH2 NH--, a group --CH(OH)--, a group --CHF-- or a group --CH(OCH3)--, and n is equal to 6 or 8, and their addition salts. These novel compounds are useful especially as immunosuppressants. The invention further relates to the method of preparing said compounds.
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