- SMALL MOLECULE ANTAGONISTS OF SUMO RELATED MODIFICATION OF CRMP2 AND USES THEREOF
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This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperidinyl-benzoimidazole structure which function as antagonists of small ubiquitin like modifier (SUMO) related modification (SUMOylation) of collapsin response mediator protein 2 (CRMP2), and their use as therapeutics for the treatment of voltage gated sodium channel 1.7 (Nav1.7) related itch, anosmia, migraine event, and/or pain (e.g., neuropathic pain).
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- 3,5-Bis(benzylidene)-4-piperidones and related N-acyl analogs: A novel cluster of antimalarials targeting the liver stage of Plasmodium falciparum
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Drug resistance is a major challenge in antimalarial chemotherapy. In addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. There are only a few antimalarials that target the liver stage of the Plasmodium species which is an essential part of the life cycle of the malarial parasite. We report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related N-acyl analogs 1-5, a number of which exhibit potent in vitro growth-inhibiting properties towards drug-sensitive D6 and drug-resistant C235 strains of Plasmodium falciparum as well as inhibiting the liver stage development of the malarial life cycle. The compounds 2b (IC50: 165 ng/mL), 3b (IC50: 186 ng/mL), 5c (IC50: 159 ng/mL) and 5d (IC50: 93.5 ng/mL) emerged as lead molecules that inhibit liver stage Plasmodium berghei and are significantly more potent than chloroquine (IC50: >2000 ng/mL) and mefloquine (IC50: >2000 ng/mL) in this screen. All the compounds that showed potent inhibitory activity against the P. berghei liver stage were nontoxic to human HepG2 liver cells (IC50: >2000 ng/mL). The compounds 5a and 5b exhibit comparable metabolic stability as chloroquine and mefloquine in human plasma and the most potent compound 5d demonstrated suitable permeability characteristics using the MDCK monolayer. These results emphasize the value of 3,5-bis(benzylidene)-4-piperidones as novel antimalarials for further drug development.
- Das, Umashankar,Singh, Ravi S.P.,Alcorn, Jane,Hickman, Mark R.,Sciotti, Richard J.,Leed, Susan E.,Lee, Patricia J.,Roncal, Norma,Dimmock, Jonathan R.
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p. 7250 - 7256
(2013/11/19)
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- Design, synthesis and cytotoxic properties of novel 1-[4-(2-alkylaminoethoxy)phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones and related compounds
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The 3,5-bis(arylidene)-4-piperidones 1 contain the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore which is considered to interact at a complementary binding site in susceptible neoplasms. The hypothesis was formulated that the presence of an acyl group attached to the piperidyl nitrogen atom in series 1 may interact with an additional binding site thereby enhancing cytotoxic potencies. This concept led to the synthesis of various N-acyl-3,5-bis(arylidene)-4-piperidones 3-7 many of which displayed significant cytotoxicity towards a variety of cancer cell lines. A comparison of the potencies between the compounds in series 1 and the related nonquaternary analogues 3-6 revealed that in approximately half of the comparisons made, the N-acyl analogues had increased potencies.
- Das, Umashankar,Alcorn, Jane,Shrivastav, Anuraag,Sharma, Rajendra K.,De Clercq, Erik,Balzarini, Jan,Dimmock, Jonathan R.
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- Process for preparing benzoic acids
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An improved process for the preparation of 4[(2-piperidin-1-yl)ethoxy]benzoic acid derivatives, comprising reacting a haloalkyl amine of formula (III) with a compound of formula (IV) in the presence of a hydrated inorganic base in an appropriate solvent.
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Page/Page column 4-7
(2010/02/12)
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- SELECTIVE ESTROGEN RECEPTOR MODULATORS
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The present invention provides a compound represented by the following formula (I); [wherein T represents a single bond, a C1-C4 alkylene group which may have a substituent and the like; formula (I-1) represents a single bond or a double bond; A represents a single bond, a bivalent 5- to 14-membered heterocyclic group which may have a substituent and the like; Y represents a single bond and the like; Z represents a methylene group and the like; ring G represents a phenylene group and the like which may condense with a 5- to 6-membered ring and may have a heteroatom; Ra and Rb are the same as or different from each other and represent a hydrogen atom and the like; W represents a single bond and the like; R' represents 1 to 4 independent hydrogen atoms and the like; and R" represents 1 to 4 independent hydrogen atoms and the like] or a salt thereof, or a hydrate thereof.
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Page/Page column 83
(2008/06/13)
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- Process for the synthesis of vinyl sulfoxides
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The present invention is directed to a new process for the synthesis of vinyl sulfoxides, in particular diarylvinyl sulfoxides
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Page column 16
(2010/01/31)
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- Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceuticals
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The invention relates to intermediates and processes for producing benzothiophenes employing hydroxylamines.
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- Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceuticals
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The invention relates to novel intermediates of formula VI wherein R1and R2each are independently C1-C4alkyl, or R1and R2together with the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino ring; n is 2 or 3; and Y1is p-toluenesulfonyl-O-, methylsulfonyl-O-, trifluoromethylsulfonyl-O-, 2,2,2-trifluoroethylsulfonyl-O-, or trifluoroacetyl-O-; or a salt or solvate thereof. and processes for producing benzothiophenes of formula II wherein R4and R5are each independently a hydroxy protecting group.
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- Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceutical agents
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Novel processes for producing compounds of formula I STR1 wherein R1 and R2 each are independently C1 -C4 alkyl, or combine to form piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; and n is 2 or 3; or a pharmaceutically acceptable salt thereof employing alkylacetate solvents are provided.
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- Process for the synthesis of benzo[b]thiophenes
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The present invention is directed to new processes for the synthesis of 2-aryl benzo[b]thiophenes.
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- Process for the synthesis of benzo[b]thiophenes
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The present invention is directed to a process for the synthesis of 2-arylbenzo[b]thiophenes.
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- Diarylvinyl sulfoxides
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The present invention is directed to new diarylvinyl sulfoxides.
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- Benzothiphene derivatives for treating resistant tumors
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This invention provides a series of substituted benzo[b]thiophenes useful in reversing multidrug resistance in a resistant neoplasm. The present invention also provides methods for reversing the multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted benzothiophene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted benzothiophene in combination with an oncolytic agent.
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- Process for the synthesis of vinyl sulfenic acid derivatives
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The present invention is directed to a new process for the synthesis of vinyl sulfenic acid derivatives. These compounds are useful for the synthesis of benzo b!thiophenes, in particular 2-aryl-benzo b!thiophenes.
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- Process for the synthesis of benzo[b]thiophenes
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The present invention is directed to a new process for the synthesis of 2-aryl benzo[b]thiophenes, and to novel intermediates therefor.
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