- Solid-phase synthetic method for N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives
-
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
-
-
Read Online
- Discovery of an Orally Active and Long-Acting DPP-IV Inhibitor through Property-Based Optimization with an in Silico Biotransformation Prediction Tool
-
Long-acting dipeptidyl peptidase IV inhibitors have emerged as promising molecules for interventions for type 2 diabetes. Once weekly dosing brings greater patient compliance and more stable glycemic control. Starting from our previous highly potent compound with a thienoprimidine scaffold, which is unfortunately severely hit by hepatic biotransformation, a lead compound was rapidly generated by drawing on the experience of our previously discovered long-acting compounds with pyrrolopyrimidine scaffold. With the aid of an in silico biotransformation prediction tool, (R)-2-((2-(3-aminopiperidin-1-yl)-4-oxo-6-(pyridin-3-yl)thieno[3,2-d]pyrimidin-3(4H)-yl)methyl)-4-fluorobenzonitrile was eventually generated and determined to have high potency, a fine pharmacokinetic profile, and a long-acting in vivo efficacy.
- Zeng, Shaogao,Dou, Wenyuan,Li, Manna,Zhou, Yang,Guo, Jiehuang,Zhao, Nan,Huang, Hong,Zhou, Qiaoli,Hu, Wenhui,Ma, Yanfang,Zhao, Xin,Xie, Hui
-
-
Read Online
- SMALL MOLECULE COVALENT ACTIVATORS OF UCP1
-
Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof. The compounds of Formula (I) are useful for activating uncoupling protein 1 (UCP1) dependent thermogenesis. Also disclosed herein are methods of treating obesity
- -
-
Page/Page column 33-34
(2022/01/05)
-
- Thienopyrimidinone compound or pharmaceutically-acceptable salt thereof and preparation method and application thereof
-
The invention provides a thienopyrimidinone compound or pharmaceutically-acceptable salt thereof and a preparation method and application thereof. The thienopyrimidinone compound or the pharmaceutically-acceptable salt thereof has a novel chemical structure, it is verified through in-vitro and in-vivo experiments that a very good selective inhibiting effect on DPP-IV is achieved, the activity of DPP-VIII and DPP-IX is barely affected while the activity of DPP-IV is effectively inhibited, meanwhile, the inhibition ratio of a potassium ion channel is low, and it can be predicted that the toxicity is low after the compound is developed into medicine. Compared with medicine trelagliptin orally taken once every week on the market, the thienopyrimidinone compound has fairly high or higher bioavailable efficiency, it can be predicted that after the compound is developed, the treatment effect that the compound is orally taken once for a long time, and the convenience and compliance of a patient are greatly improved. The preparation method is simple, the raw materials are easy to obtain, and the preparation method is suitable for industrial large-scale production.
- -
-
Paragraph 0145-0147; 0153-0155
(2019/01/23)
-
- Thienopyridone derivative, method for preparing the same and pharmaceutical composition comprising the same
-
The present invention relates to a thienopyridone derivative, a production method thereof, and a pharmaceutical composition comprising the same and, more particularly, to a novel thienopyridone derivative comprising various substituents, a production method thereof, and a pharmaceutical composition for preventing or treating cancer, comprising the same as active ingredient.COPYRIGHT KIPO 2017
- -
-
Paragraph 0208-0210
(2017/09/02)
-
- HETEROCYCLIC COMPOUND
-
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.
- -
-
-
- NOVEL 3,4,4A,10B-TETRAHYDRO-1H-THIOPYRANO[4,3-C]ISOQUINOLINE COMPOUNDS
-
The compounds of formula (1), in which A, X, R1, R2, R3 and R7 have the meanings as given in the description, are novel effective inhibitors of type 4 and 5 phosphodiesterase.
- -
-
Page/Page column 35
(2013/02/28)
-
- THIENOPYRIMIDINE AS CDC7 KINASE INHIBITORS
-
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
- -
-
Page/Page column 130-131
(2010/09/18)
-
- THIENOPYRIDINE AND THIAZOLOPYRIDINE DERIVATIVES THAT INHIBIT PROLYL HYDROXYLASE ACTIVITY
-
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.
- -
-
Page/Page column 45-46
(2009/01/20)
-
- Thienopyrimidinone bis-aminopyrrolidine ureas as potent melanin-concentrating hormone receptor-1 (MCH-R1) antagonists
-
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.
-
p. 2535 - 2539
(2008/02/01)
-
- Melanin concentrating hormone antagonists
-
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.
- -
-
Page/Page column 9
(2008/06/13)
-
- NOVEL AMINO ALCOHOL-SUBSTITUTED ARYLTHIENOPYRIMIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
-
The invention relates to amino alcohol-substituted arylthienopyrimidinones and their derivatives, and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one amino alcohol-su
- -
-
Page/Page column 74; 116
(2008/06/13)
-
- SUBSTITUTED THIOPHENE DERIVATIVES AS ANTI-CANCER AGENTS
-
The present invention relates to new substituted five-membered compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds
- -
-
Page/Page column 110
(2008/06/13)
-
- MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS AND COMPOSITIONS AND METHODS RELATED THERETO
-
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.
- -
-
Page/Page column 29
(2008/06/13)
-
- HETERORYL-FUSED PYRIMIDINYL COMPOUNDS AS ANTICANCER AGENTS
-
Heteroaryl-fused pyrimidinyl compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the heteroaryl-fused pyrimidinyl compounds, either alone or in combination
- -
-
Page/Page column 38
(2008/06/13)
-
- Antihypertensive thienopyridines
-
Novel thienopyridones with antihypertensive activity have the formula I, STR1 wherein the ring A represents an optionally substituted thiophene ring; m is 0 or 1; n is 0, 1 or 2; R is lower alkyl and R1 is lower alkyl. The fused thieno-ring may
- -
-
-