- COMPOSITIONS CONTAINING, METHODS AND USES OF ANTIBODY-TLR AGONIST CONJUGATES
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Disclosed herein are Trastuzumab-linked TLR-agonist derivative analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The Trastuzumab-linked TLR-agonist derivative analogs can includ
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- COMPOUNDS AS INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR
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The present invention provides compounds of Formula (I) shown above and their pharmaceutically acceptable salt, solvates, isomers, or prodrugs, as well as pharmaceutical compositions containing these compounds. Also provided by the invention is a method for treating a disorder mediated by macrophage migration inhibitory factor in a subject, comprising administering to the subject in need thereof a compound or a pharmaceutical composition of this invention.
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- PURINE AND 3-DEAZAPURINE ANALOGUES AS CHOLINE KINASE INHIBITORS
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There are provided substituted purine and 3-deazapurine analogues, which modulate the activity of Choline Kinase (ChoK). The compounds of this invention are therefore useful in treating diseases caused by an altered choline metabolism, such as cancer, cell proliferative disorders, infectious diseases of different origin, immune-related disorders and neurodegenerative disorders. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.
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- ADENINE DERIVATIVES WHICH ARE USEFUL IN THE TREATMENT OF ALLERGIC DISEASES OR OTHER INFLAMMATORY CONDITIONS
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Compounds of formula (I).
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- Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives
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We report the synthesis and biological evaluation of a new series of 8-oxoadenines substituted at the 9-position with a 4-piperidinylalkyl moiety. In vitro evaluation of the piperidinyl-substituted oxoadenines 3a-g in human TLR7- or TLR8-transfected HEK293 cells and in human PBMCs indicated that TLR7/8 selectivity/potency and cytokine induction can be modulated by varying the length of the alkyl linker. Oxoadenine 3f containing a 5-carbon linker was found to be the most potent TLR7 agonist and IFNα inducer in the series whereas 3b possessing a 1-carbon linker was the most potent TLR8 agonist.
- Bazin, Hélène G.,Li, Yufeng,Khalaf, Juhienah K.,Mwakwari, Sandra,Livesay, Mark T.,Evans, Jay T.,Johnson, David A.
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p. 1318 - 1323
(2015/04/14)
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- NITROGEN CONTAINING HETEROCYCLIC COMPOUNDS AS PIK3 -DELTA INHIBITORS
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Substituted bicyclic heteroaryls of the following formulae and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory o
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Page/Page column 60
(2012/01/15)
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- PROCESS FOR PREPARING ADENINE COMPOUNDS AND INTERMEDIATES THEREOF
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The present invention relates to a process for preparing a compound of Formula (III), or a salt thereof; wherein R1 is C1-6 alkyl; R2 and R3 are each independently hydrogen or C1-4 alkyl, or R2 and R3 combine together with the nitrogen atom to which they are attached to form a pyrrolidine ring, a morpholine ring, a piperidine ring, or a piperazine ring; and n is 1, 2 or 3.
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Page/Page column 22;23
(2012/02/05)
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- PURINE DERIVATIVES AND THEIR PHARMACEUTICAL USES
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Compounds of formula (I), wherein; R1 represents hydrogen or C1-3alkyl; n is an integer having a value of 1 to 5; X represents O or NH; Y represents C or N; or a pharmaceutically acceptable salt thereof, have been shown to be inducers of human interferon
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- 6-AMINO-2-{ [ (1S)-1-METHYLBUTYL] OXY}-9-[5-(1-PIPERIDINYL)-7,9-DIHYDRO-8H-PURIN-8-ONE MALEATE
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A compound which is 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one: Formula (I) in the form of a maleate salt, may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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- PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
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Compounds of formula (I): wherein R1 is C1-6alkylamino, or C1-6alkoxy; m is an integer having a value of 3, 4, or 5; n is an integer having a value of 0 to 3; p is an integer having a value of 1 or 2 and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 41
(2010/04/03)
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- PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
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Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 43
(2010/04/03)
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- PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
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Compounds of Formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; m is an integer having a value of 2 to 6; R2 is hydrogen, C1-6alkyl, or C3-7cycloalkylC0-6alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 43
(2010/04/03)
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- COMPOUNDS
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Compounds of formula (I): wherein R1 is C1-6alkylamino, or C1-6alkoxy; m is an integer having a value of 2 or 3; n is an integer having a value of 0 to 3; p is an integer having a value of 1 or 2; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 38
(2010/04/03)
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- NOVEL ADENINE DERIVATIVES
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Compounds of formula (I) wherein R1 is C1-6alkylamino, or C1-6alkoxy; R2 is a group having the structure (II): n is an integer having a value of 1 to 6; Het is a 6-membered saturated heterocycle containing one nitrogen atom wherein Het is attached to the -(CH2)n- moiety at any carbon atom of the heterocycle; R3 is hydrogen, C1-8alkyl, or C3-7cycloalkylC0-6alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 50
(2010/04/03)
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- Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family
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Adenine derivatives bearing substituents in the 2-, N6-, 7-, 8-, and/or 9-position and a series of deazapurines were synthesized and investigated in [3H]adenine binding studies at the adenine receptor in rat brain cortical membrane preparations (rAde1R). Steep structure-activity relationships were observed. Substitution in the 8-position (amino, dimethylamino, piperidinyl, piperazinyl) or in the 9-position (2-morpholinoethyl) with basic residues or introduction of polar substituents at the 6-amino function (hydroxy, amino, acetyl) represented the best modifications. Functional evaluation of selected adenine derivatives in adenylate cyclase assays at 1321N1 astrocytoma cells stably expressing the rAde1R showed that all compounds investigated were agonists or partial agonists. A subset of compounds was additionally investigated in binding studies at human embryonic kidney (HEK293) cells, which also express a high-affinity adenine binding site. Structure-affinity relationships at the human cell line were similar to those at the rAde1R, but not identical. In particular, N 6-acetyladenine (25, Ki rat: 2.85 μM; Ki human: 0.515 μM) and 8-aminoadenine (33, Ki rat: 6.51 μM; Ki human: 0.0341 μM) were much more potent at the human as compared to the rat binding site. The new AdeR ligands may serve as lead structures and contribute to the elucidation of the functions of the adenine receptor family. 2009 American Chemical Society.
- Borrmann, Thomas,Abdelrahman, Aliaa,Volpini, Rosaria,Lambertucci, Catia,Alksnis, Edgars,Gorzalka, Simone,Knospe, Melanie,Schiedel, Anke C.,Cristalli, Gloria,Müller, Christa E.
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experimental part
p. 5974 - 5989
(2010/03/24)
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- NOVEL ADENINE COMPOUND
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A novel adenine compound represented by the formula (1): wherein A represents an (un)substituted aromatic carbocycle or (un)substituted aromatic heterocycle; L1 and L2 each independently represents straighted or branched alkylene, et
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Page/Page column 30
(2009/12/27)
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- PURINE DERIVATIVES AS IMMUNOMODULATORS
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The present invention includes novel compounds useful in the treatment of various disorders in particular infectious diseases, cancer, and allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, and as vaccine adjuvants
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- 8-OXOADENINE DERIVATIVES ACTING AS MODULATORS OF TLR7
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The present invention provides 8-oxoadenine derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The 8-oxoadenine derivatives act as modulators of Toll-like Receptor (TLR) 7 and thus may be us
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Page/Page column 34
(2008/06/13)
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- 8-OXOADENINE DERIVATIVES AS IMMUNO-MODULATORS
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The present invention provides compounds of formula (I), wherein R1, Y1, X1, Z1, X2, Y2, A, n and R2 are as defined in the specification, processes for their preparation, pharmac
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Page/Page column 23
(2008/12/06)
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- NOVEL ADENINE COMPOUND
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A novel adenine compound represented by the formula (1): wherein Z represents (un)substituted alkylene, a single bond, etc.; R1 represents an (un)substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heteroaryl group; R2 represen
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Page/Page column 22-23
(2008/12/06)
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- 9-SUBSTITUTED-8-OXO-ADENINE COMPOUNDS AS TOLL-LIKE RECEPTOR (TLR7) MODULATORS
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The present invention provides compounds of formula (I): wherein R1, Y1, X1, L and R2 are as defined in the specification, and pharmaceutically acceptable salts thereof, as well as processes for their preparation, pharmaceutical compositions containing them and their use as modulation of toll-like receptor (especially TLR7).
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Page/Page column 11; 35
(2008/12/07)
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- 9-SUBSTITUTED-8-OXO-ADENINE COMPOUNDS AS TOLL-LIKE RECEPTOR (TLR7) MODULATORS
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The present invention provides compounds of formula (I), where n, R1, R2, A, X1, Y1, Z1, X2 and Y2 are as defined in the specification, processes for their preparation, pharmaceu
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Page/Page column 22; 37
(2008/12/07)
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- PURINE DERIVATIVES FOR THE TREATMENT OF VIRAL OR ALLERGIC DISEASES AND CANCERS
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The present invention provides compounds of (I) wherein R1, Y1, X1, Z1, X2, Y2, A, Y3, n, R and R2 are as defined in the specification, processes for their preparation
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Page/Page column 13; 30
(2008/06/13)
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- PURINE DERIVATIVES HAVING IMMUNO-MODULATING PROPERTIES
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The present invention provides compounds of formula (I) wherein n, Y, Z, R, R1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in t
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Page/Page column 26-27
(2008/06/13)
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- 8-OXOADENINE COMPOUND
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An 8-oxoadenine compound useful as an immuno-modulator having specific activity against Th1/Th2, specifically a prophylactic and therapeutic agent for a topical application for allergic diseases, viral siseases and cancers, which is represented by the following formula (1): , wherein A is a group of a formula represented by the formula (2): , wherein R2 is a substituted or unsubstituted alkyl group and so on, R3 is hydrogen atom or an alkyl group, R is a halogen atom and so on, n is 0-2, X1 is oxygen atom, Z is straight or branched chain alkylene, and R1 is an alkyl group which is optionally substituted by hydroxy group, an alkoxy group, alkoxycarbonyl group and so on, or its pharmaceutically acceptable salt.
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Page/Page column 147
(2010/11/24)
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- 9-SUBSTITUTED 8-OXOADENINE COMPOUND
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The present invention provides an 8-oxoadenine compound having immunemodulating activities such as an interferon inducing activity and useful as an antiviral agent and antiallergic agent, which is represented by the following formula (1): [wherein the ring A represents a 6-10 membered aromatic carbocyclic ring and the like, R represents a halogen atom, an alkyl group and the like, n represents an integer of 0-2, Z 1 represents alkylene, X 2 represents oxygen atom, sulfur atom, SO 2 , NR 5 , CO, CONR 5 , NR 5 CO and the like, Y 1 , Y 2 and Y 3 represent independently a single bond or an alkylene group, X 1 represents oxygen atom, sulfur atom, NR 4 (R 4 is hydrogen atom or an alkyl group) or a single bond, R 2 represents a substituted or unsubstituted alkyl group, R 1 represents hydrogen atom, hydroxy group, an alkoxy group, an alkoxycarbonyl group or a haloalkyl group] or its pharmaceutically acceptable salt.
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Page/Page column 53
(2010/11/24)
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