- FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compound-linker constructs and antibody-drug-conjugates of compounds of formula (I) that are useful as modulators of STING (Stimulator of Interferon Genes).
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Page/Page column 267-268
(2021/06/22)
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- Discovery of 1,2,4-thiadiazolidine-3,5-dione analogs that exhibit unusual and selective rapid cell death kinetics against acute myelogenous leukemia cells in culture
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4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) was previously identified as an antileukemic agent exhibiting no evident toxicity toward normal hematopoietic cells. An SAR study has been carried out to examine the effect of varying the C-2 and
- Nasim, Shama,Guzman, Monica L.,Jordan, Craig T.,Crooks, Peter A.
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p. 4879 - 4883
(2011/09/16)
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- HISTONE LYSINE DEMETHYLASE INHIBITORS
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The invention provides a compound which is an iV-oxalylglycine derivative of formula (I): a hydroxamic acid derivative of formula (II): or a heteroaryl derivative of fomula (III): wherein n; Z1; Z2; Y1; Y2; A; p; X1; X2; m; R4; B; R5; R6; R7; R8; R9; X3; R10; R11 and R12 are as defined herein, or a pharmaceutically acceptable salt thereof. These compounds are inhibitors of the human 2-oxoglutarate-dependant JMJD2 subfamily of histone demethylases, in particular JMJD2E. Such inhibitors are useful in changing the epigenetic state of cells resulting in the inhibition / activation of chromatin remodelling, multiple gene activation / deactivation, and in treating cancer and other conditions characterised by undesirable cellular proliferation, and psychiatric disorders including depression.
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Page/Page column 84-85
(2010/04/30)
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- A method for the selective protection of aromatic amines in the presence of aliphatic amines
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A simple and efficient procedure has been developed for the regioselective protection of aromatic amines in the presence of aliphatic amines. The method is general for the preparation of mono-N-Boc, -N-Cbz, -N-Fmoc or -N-Alloc aromatic amines in high yield without affecting the aliphatic amines. This approach is applicable to substituted (aminoalkyl)aniline compounds with different functionalities and was employed to supply gram quantities of the protected aniline product. Georg Thieme Verlag Stuttgart · New York.
- Perron, Valerie,Abbott, Shaun,Moreau, Nancie,Lee, Devin,Penney, Christopher,Zacharie, Boulos
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experimental part
p. 283 - 289
(2009/06/25)
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- 6-ARYLALKYLAMINO- 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS
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The present invention provides 6-substituted 2,3,4,5-tetrahydro-lH- benzo[d]azepines of Formula (I) as selective 5-HT2c receptor agonists for the treatment of 5-HT2c associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety, where, R6 is -NR10R11, where R10 is substituted phenylalkyl or substituted pyridylalkyl and other substituents are as defined in the specification.
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Page/Page column 112
(2010/11/26)
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- Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists
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The structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. A docking model of potent antagonist 2 with the sensor region of TRPV1 is proposed.
- Lee, Jeewoo,Jin, Mi-Kyoung,Kang, Sang-Uk,Su, Yeon Kim,Lee, Jiyoun,Shin, Myoungyoup,Hwang, Jaemin,Cho, Sookhyun,Choi, Yeon-Sil,Choi, Hyun-Kyung,Kim, Sung-Eun,Suh, Young-Ger,Lee, Yong-Sil,Kim, Young-Ho,Ha, Hee-Jin,Toth, Attila,Pearce, Larry V.,Tran, Richard,Szabo, Tamas,Welter, Jacqueline D.,Lundberg, Daniel J.,Wang, Yun,Lazar, Jozsef,Pavlyukovets, Vladimir A.,Morgan, Matthew A.,Blumberg, Peter M.
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p. 4143 - 4150
(2007/10/03)
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- Selective nitrolytic deprotection of N-BOC-amines and N-BOC-amino acids derivatives
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The extension of the deprotection procedure using HNO3 in CH2Cl2 to a number of appropriately selected N-BOC-masked amines and derivatives of natural amino acids was investigated. The method was found to work effectively with almost all tested substrates, with the exception of activated aromatic amines and heterocycles which underwent unavoidable faster oxidation. Alanine, phenylalanine, serine and lysine derivatives were efficiently deprotected, as well as dipeptide Ala-Phe, preserving the configuration of the substrates and without affecting copresent Z and ester functions, with a remarkable selectivity towards acid sensitive t-butyl esters. The obtained amino acids esters, isolated and characterized in the form of nitrates salts, proved to be suitable intermediates to be used in peptide synthesis.
- Strazzolini, Paolo,Melloni, Tiziana,Giumanini, Angelo G
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p. 9033 - 9043
(2007/10/03)
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- Structure-Activity Relationships of N6-Benzyladenosine-5'-uronamides as A3-Selective Adenosine Agonists
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Adenosine analogues modified at the 5'-position as uronamides and/or as N6-benzyl derivatives were synthesized.These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A3 adenosine receptor and at rat brain A1 and A2a receptors. 5'-Uronamide substituents favored A3 selectivity in the order N-methyl > N-ethyl ca. unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N6-benzyladenosine was 37-56-fold more selective for A3 receptors.Potency at A3 receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N6-(3-substitutedbenzyl)adenosines are optimal for potency and selectivity at A3 receptors.A series of 3-(halobenzyl)-5'-N-ethyluronamide derivatives showed the order of potency at A1 and A2a receptors of I ca.Br > Cl > F.At A3 receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N6-(3-iodobenzyl)adenosine displayed a Ki value of 1.1 nM at A3 receptors and selectivity versus A1 and A2a receptors of 50-fold.A series of methoxybenzyl derivatives showed that a 4-methoxy group best favored A3 selectivity.A 4-sulfobenzyl derivative was a specific ligand at A3 receptors of moderate potency.An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking.
- Gallo-Rodriguez, Carola,Ji, Xiao-duo,Melman, Neli,Siegman, Barry D.,Sanders, Lawrence H.,et al.
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p. 636 - 646
(2007/10/02)
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