- Solid-phase synthetic method for N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives
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Herein, we describe a solid-phase synthetic method for synthesizing N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives. The derivatives consist of the biologically active 6-phenylthieno[3,2-d]pyrimidine scaffold. The template mediated synthetic strategy involving Suzuki coupling reactions between methyl 3-amino-5-bromothiophene-2-carboxylate and arylboronic acids afforded methyl 3-amino-5-arylthiophene-2-carboxylates. Cyclocondensation reactions involving methyl 3-amino-5-arylthiophene-2-carboxylates and methyl cyanoformate afforded esters, that when subjected to hydrolysis reactions yielded 6-aryl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-carboxylic acids (template compounds). These carboxylic acid templates were coupled with primary alkylamine-loaded acid-sensitive methoxybenzaldehyde (AMEBA) resins. The amide coupling reactions were followed by direct amination reactions mediated by benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP). The compounds were subsequently cleaved from the solid support, purified using the reverse phase-high performance liquid chromatography technique (RP-HPLC), and passed through a strong anion exchange (SAX) resin pretreated with water to yield the N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives. The reaction conditions for the solid-phase transformations were optimized using a solution-phase model using 2,4-dimethoxybenzyl-protected isobutylamine as a reactant. 2,4-Dimethoxybenzyl-protected isobutylamine, and not AMEBA resin-loaded isobutylamine was used during the process. Substituent variation experiments were performed using 6-aryl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-carboxylic acids and a variety of primary and secondary amine building blocks. Additionally, we could include the Suzuki coupling step in a modified solid-phase synthetic sequence.
- Ahn, Seohyeon,Jeon, Moon-Kook
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- HETEROCYCLIC COMPOUND
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Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.
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- THIENOPYRIMIDINE AS CDC7 KINASE INHIBITORS
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The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer
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Page/Page column 130
(2010/09/18)
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- THIENOPYRIDINE AND THIAZOLOPYRIDINE DERIVATIVES THAT INHIBIT PROLYL HYDROXYLASE ACTIVITY
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Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure:(I) where the definitions of the variables are provided herein.
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Page/Page column 45-46
(2009/01/20)
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- Thienopyrimidinone bis-aminopyrrolidine ureas as potent melanin-concentrating hormone receptor-1 (MCH-R1) antagonists
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A series of thienopyrimidinone bis-aminopyrrolidine ureas were designed, synthesized, and evaluated for their ability to bind melanin-concentrating hormone receptor-1. These compounds exhibit potent binding affinity (Ki = 3 nM) and good in vitro metabolic stability.
- Zhang, Mingzhu,Tamiya, Junko,Nguyen, Linh,Rowbottom, Martin W.,Dyck, Brian,Vickers, Troy D.,Grey, Jonathan,Schwarz, David A.,Heise, Christopher E.,Haelewyn, Jason,Mistry, Monica S.,Goodfellow, Val S.
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p. 2535 - 2539
(2008/02/01)
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- Melanin concentrating hormone antagonists
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The present invention relates to compounds capable of serving as moderators of human and mammalian appetite and as such provide a means for reducing body mass and controlling obesity.
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Page/Page column 9
(2008/06/13)
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- MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS AND COMPOSITIONS AND METHODS RELATED THERETO
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Melanin-concentrating hormone (MCH) receptor antagonists are disclosed having utility for the treatment of MCH receptor-based disorders such as obesity. The compounds of this invention have the following structure of formula (I) including pharmaceutically acceptable salts, esters, solvates, stereoisomers, and prodrugs thereof, wherein m, n, Q1, Q2, R1, R2, R3, R4, R7 and X are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.
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Page/Page column 29
(2008/06/13)
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