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Author

Amedeo Arturo Failli

Other affiliations: Columbia University
Bio: Amedeo Arturo Failli is an academic researcher from Princeton University. The author has contributed to research in topics: Alkyl & Indole test. The author has an hindex of 21, co-authored 74 publications receiving 1809 citations. Previous affiliations of Amedeo Arturo Failli include Columbia University.


Papers
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Patent
25 Mar 1992
TL;DR: In this article, a method of using rapamycin 42-[O-[(1, 1-dimethylethyl)-dimethylsilyl] ether for the preparation of 31-substituted Rapamycin derivatives was presented.
Abstract: A compound of the structure ##STR1## wherein R 1 is --SiR 3 R 4 R 5 ; R 2 is hydrogen or --SiR 3 R 4 R 5 ; and R 3 , R 4 , and R 5 are each, independently, alkyl, alkenyl, aralkyl, triphenylmethyl, or phenyl which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases and diseases of inflammation; by virtue of its antitumor activity is useful in treating solid tumors; and by virtue of its antifungal activity is useful in treating fungal infections. This invention also provides a method of using rapamycin 42-[O-[(1,1-dimethylethyl)-dimethylsilyl] ether for the preparation of 31-substituted rapamycin derivatives.

207 citations

Patent
05 Mar 1992
TL;DR: A rapamycin derivative is a derivative of Rapamycin of general formula (I) where R1 is alkyl, alkenyl, or alkynyl containing 1 to 6 carbon atoms; or an aromatic moiety selected from the group consisting of phenyl and naphthyl or a heterocyclic moiety selecting from the groups consisting of thiophenyl and quinolinyl or NHCO2 R2 wherein R2 is lower alkyls containing 1-6 carbon atoms or a pharmaceutically acceptable salt thereof.
Abstract: A derivative of rapamycin of general formula (I) ##STR1## where R1 is alkyl, alkenyl, or alkynyl containing 1 to 6 carbon atoms; or an aromatic moiety selected from the group consisting of phenyl and naphthyl or a heterocyclic moiety selected from the group consisting of thiophenyl and quinolinyl or NHCO2 R2 wherein R2 is lower alkyl containing 1 to 6 carbon atoms or a pharmaceutically acceptable salt thereof, which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host versus graft disease, autoimmune diseases, and diseases of inflammation.

141 citations

Patent
19 Sep 1991
TL;DR: A compound of structure (I) is defined as a compound of which the substituent is selected from alkyl, aralkyl, fluorenylmethyl, or phenyl which is optionally mono-, di-, or tri-substituted.
Abstract: A compound of structure (I), wherein R?1, R2, and R3? are each, independently, hydrogen, or R4; R4 is (a), (b), or (c); R5 is hydrogen, alkyl, aralkyl, -(CH?2?)qCO2R?8?, -(CH?2?)rNR?9CO?2R10, carbamylalkyl, aminoalkyl, hydroxyalkyl, guanylalkyl, mercaptoalkyl, alkylthioalkyl, indolylmethyl, hydroxypehnylmethyl, imidazoylmethyl or phenyl which is optionally mono-, di-, or tri-substituted with a substituent selected from alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, amino, or a carboxylic acid; R?6 and R9? are each, independently, hydrogen, alkyl, or aralkyl; R?7, R8, and R10? are each, independently, alkyl, aralkyl, fluorenylmethyl, or phenyl which is optionally mono-, di-, or tri-substituted; R?11 and R12? are each, independently, alkyl, aralkyl, or phenyl which is optionally mono-, di-, or tri-substituted; X is (d), O, or S; R?13? and R?14? are each, independently, hydrogen or alkyl; Y is CH or N; m is 0-4; n is 0-4; p is 1-2; q is 0-4; r is 0-4; t is 0-4; u is 0-4; wherein R5, R6, m, and n are independent in each of (e) subunits when p=2; or a pharmaceutically acceptable salt thereof, with the proviso that R?1, R2, and R3? are not all hydrogen, further provided that R?1, R2 and R3? are not all (a), and still further provided that t and u are not both 0 when X is O or S, which by virtue of its immuno-suppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases, and diseases of inflammation, and by virtue of its antifungal activity is useful in treating fungal infections.

118 citations

Patent
11 Sep 1991
TL;DR: A compound of the structure (I) wherein R1 is (II); R3 is hydrogen, alkyl, arylalkyl, (CH?2?)sNR?4R5?, aminoalkyl and hydroxyalkyl.
Abstract: A compound of the structure (I) wherein R1 is (II); R3 is hydrogen, alkyl, arylalkyl, (CH?2?)sNR?4R5?, aminoalkyl, hydroxyalkyl, guanylalkyl, mercaptoalkyl, alkylthioalkyl, indolylmethyl, hydroxyphenylmethyl, imidazolylmethyl or phenyl which is optionally substituted; R4 is hydrogen, alkyl, or aralkyl; R?2 and R5? are each independently hydrogen, formyl, alkanoyl, arylalkanoyl, aryloyl, or CO?2R?6; R6 is alkyl, arylalkyl, allyl, fluorenylmethyl, or phenyl which is optionally substituted; m is 0-4; n is 0-4; p is 0-1; q is 0-4; r is 0-4; and s is 0-4; or a pharmaceutically acceptable salt thereof, which by virtue of its immuno- suppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases, and diseases of inflammation, by virtue of its antifungal activity is useful in treating fungal infections; and by virtue of its antitumor activity is useful in treating tumors.

98 citations

Patent
27 Oct 1990
TL;DR: There are disclosed compounds of the formula: A(CH2)nO-B, wherein A is C4-C8 alkyl, phenoxyethyl, phenoxyphenyl or a group having formula (a) or (b), wherein X is -N- or (c); Z is (d), (e), (f), (g), -S- or -O-; R1 is hydrogen, lower alkyls, phenyl, or phenyl substituted with trifluoromethyl; R2 is hydrogen or lower al
Abstract: There are disclosed compounds of the formula: A(CH2)nO-B, wherein A is C4-C8 alkyl, phenoxyethyl, phenoxyphenyl or a group having formula (a) or (b), wherein X is -N- or (c); Z is (d), (e), (f), (g), -S- or -O-; R1 is hydrogen, lower alkyl, phenyl or phenyl substituted with trifluoromethyl; R2 is hydrogen or lower alkyl; or R?1 and R2? taken together form a benzen ring; R3 is hydrogen or lower alkyl; n is 1-2; B is (h), (i), (j) or (k); wherein R4 is -CO?2R?2, (l), (m), (n), (o) or (p); m is 0-3; R5 is (q); or phenyl or phenyl substituted by halo, lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl; R6 is A(CH?2?)nO- or halo; with the proviso that when R?6? is halo, R5 is (r); R7 is lower alkyl; Y is -CH?2?- or -O-; R?8? is lower alkyl or -(CH?2?)mCO2R?3; R9? is (s) or -CH?2?R?10; R10? is lower alkyl, phenyl, phenyl substituted with carboxy, halo, loweralkylthio or loweralkylsulfinyl, pyridyl, furanyl or quinolinyl; R11 is lower alkyl or phenyl; and the pharmacologically acceptable salts thereof, and their use in the treatment of inflammatory conditions, such as rheumatoid arthritis, ulcerative colitis, psoriasis and other immediate hypersensitivity reactions; in the treatment of leukotriene-mediated naso-bronchial obstructive air-passageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like; and as gastric cytoprotective agents.

92 citations


Cited by
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Journal ArticleDOI
19 Apr 2004-Oncogene
TL;DR: TOR is emerging as a novel antitumor target, since the TOR inhibitor rapamycin appears to be effective against tumors resulting from aberrantly high PI3K signaling.
Abstract: Cell growth (an increase in cell mass and size through macromolecular biosynthesis) and cell cycle progression are generally tightly coupled, allowing cells to proliferate continuously while maintaining their size. The target of rapamycin (TOR) is an evolutionarily conserved kinase that integrates signals from nutrients (amino acids and energy) and growth factors (in higher eukaryotes) to regulate cell growth and cell cycle progression coordinately. In mammals, TOR is best known to regulate translation through the ribosomal protein S6 kinases (S6Ks) and the eukaryotic translation initiation factor 4E-binding proteins. Consistent with the contribution of translation to growth, TOR regulates cell, organ, and organismal size. The identification of the tumor suppressor proteins tuberous sclerosis1 and 2 (TSC1 and 2) and Ras-homolog enriched in brain (Rheb) has biochemically linked the TOR and phosphatidylinositol 3-kinase (PI3K) pathways, providing a mechanism for the crosstalk that occurs between these pathways. TOR is emerging as a novel antitumor target, since the TOR inhibitor rapamycin appears to be effective against tumors resulting from aberrantly high PI3K signaling. Not only may inhibition of TOR be effective in cancer treatment, but rapamycin is an FDA-approved immunosuppressive and cardiology drug. We review here what is known (and not known) about the function of TOR in cellular and animal physiology.

1,206 citations

Journal ArticleDOI
TL;DR: The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort.
Abstract: Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

1,107 citations

Journal ArticleDOI
TL;DR: During the last five years, new types of stable cyclic carbenes, as well as related carbon-based ligands (which are not NHCs), and which feature even stronger σ-donor properties have been developed.
Abstract: The success of homogeneous catalysis can be attributed largely to the development of a diverse range of ligand frameworks that have been used to tune the behavior of various systems. Spectacular results in this area have been achieved using cyclic diaminocarbenes (NHCs) as a result of their strong σ-donor properties. Although it is possible to cursorily tune the structure of NHCs, any diversity is still far from matching their phosphorus-based counterparts, which is one of the great strengths of the latter. A variety of stable acyclic carbenes are known, but they are either reluctant to bind metals or they give rise to fragile metal complexes. During the last five years, new types of stable cyclic carbenes, as well as related carbon-based ligands (which are not NHCs), and which feature even stronger σ-donor properties have been developed. Their synthesis and characterization as well as the stability, electronic properties, coordination behavior, and catalytic activity of the ensuing complexes are discussed, and comparisons with their NHC cousins are made.

881 citations

Journal ArticleDOI
TL;DR: The understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly, and intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights.
Abstract: The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy. Furthermore, psychostimulants such as cocaine and amphetamines have the SLC6 NTTs as primary targets. Beginning with the determination of a high-resolution structure of a prokaryotic homolog of the mammalian SLC6 transporters in 2005, the understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly. Furthermore, intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights. This review provides an update of these advances and their implications for the current understanding of the SLC6 NTTs.

697 citations