5469-69-2Relevant articles and documents
Synthesis and anti-proliferative activity studies of 2-(2-(trifluoromethyl)-6-(substituted)imidazo[1,2-b]pyridazin-3-yl)-N-(substituted)acetamide derivatives
Chavan, Sadhana L.,Chavan, Santosh L.,Gaikwad, Dattatraya D.,Pansare, Dattatraya N.,Pawar, Chandrakant D.,Pawar, Umakant D.,Shelke, Rohini N.,Zine, Ashok M.
, (2020)
A series of novel imidazo[1,2-b]pyridazin-3-yl acetamide derivatives (9a-9j) were synthesized from a 3,6-dichloropyridazine. We have developed a simple strategy for the synthesis of functionally diverse imidazole, and pyridiazine derivatives were reported via a series of steps. The work involves bicyclic imidazo-pyridazine ring formation, halogenation, cynation, hydrolysis, peptide coupling, and Buchwald reaction. The structure of the synthesized compounds was confirmed by IR, 1H NMR, 13C NMR,19F NMR, mass spectra, and elemental analysis, and purity is checked by HPLC. All synthesized compounds were screened for anticancer activity against A-549 and Du-145 cancer cell lines by MTT assay. The preliminary bioassay suggests that most of the compounds show anti-proliferation with different degrees; doxorubicin was used as positive control. The synthesized compound shows IC50 values in the range of 1.74μM to 16.17μM in both cell lines. The compounds 9e, 9g, and 9h were active compared with doxorubicin in both the cell lines. The compounds having cyclopentyl ring are active compared with higher and lower carbon analogues.
Intramolecular Diels-Alder Reactions of 1,2-Diazines: General Indoline Synthesis. Studies on the Preparation of the Central and Right-Hand Segments of CC-1065
Boger, Dale L.,Coleman, Robert S.
, p. 2240 - 2245 (1984)
An investigation of the intramolecular Diels-Alder reaction of 1,2-diazines and the application of this cycloaddition to a general synthesis of indolines is described.The use of this cycloaddition in a short, regiospecific preparation of the 1,2-dihydro-3H-pyrroloindole skeleton, the structural subunit characteristic of the antitumor antibiotic CC-1065, is detailed.
INHIBITORS OF LIN28 AND METHODS OF USE THEREOF
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Page/Page column 52; 56; 89, (2021/06/26)
The present disclosure relates to compounds of formula (I) and compositions comprising the same. The disclosure further relates to methods of treating cancers.
COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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Page/Page column 162; 163, (2020/05/15)
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol APLNR). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.
Synthesis, characterization, and antidiabetic activity of 6-methoxyimidazo[1,2-b]pyridazine derivatives
Kota, Tata Veereswara Rao,Gandham, Himabindu,Sanasi, Paul Douglas
, p. 630 - 637 (2019/02/26)
The present article describes the synthesis, characterization, and antidiabetic activity of 6-methoxyimidazo[1,2-b]pyridazine derivatives 7a-l. The synthetic sequence for the preparation of these derivatives involves the following prominent reactions: (a) Step 1: involves the high-pressure amination reaction; (b) Step 2: involves the Zinc oxide nanoparticle-catalyzed cyclization reaction; (c) Step 3: involves the methoxylation; (d) Step 4: involves the bromination reaction; (e) Step 5: involves the Suzuki coupling reaction; (f) Step 6: involves the reduction of the –NO2 group; (g) Step 7: involves Boc protection of the 1o amino group (h) Step 8: involves diazotization of the amine group and finally the last of the synthesis (i) Step 9: involves the saponification of the ethyl ester group. Furthermore, the structures of the newly synthesized 6-methoxyimidazo[1,2-b]pyridazine derivatives 7a–l were determined using 1H NMR, 13C NMR, and Mass and IR spectroscopic analyses. These derivatives were evaluated for their antidiabetic property and the results revealed that most of the compounds exhibited significant potency. It is worth mentioning that compounds 7b (69.87%), 7f (69.0%), 7h (68.79%), and 7l (68.61%) with substitution R = para-NH2, para-COOH, meta-NH2, and meta-COOH, respectively, showed significant (good) hypoglycemic activity when compared to the standard drug insulin (50 mg/kg b.w) in reducing the blood glucose level.
AMINOIMIDAZOPYRIDINES AS KINASE INHIBITORS
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Page/Page column 90, (2019/05/22)
Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, (I) are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.
CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS
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Paragraph 0198-0199, (2019/07/14)
A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Za, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.
SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Paragraph 0237; 0238, (2017/04/04)
Provided herein are novel substituted bicyclic aza-heterocycle sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
Taylor, Nicholas J.,Emer, Enrico,Preshlock, Sean,Schedler, Michael,Tredwell, Matthew,Verhoog, Stefan,Mercier, Joel,Genicot, Christophe,Gouverneur, Véronique
supporting information, p. 8267 - 8276 (2017/06/27)
Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.
PYRIDO[1,2-a]PYRIMIDONE DERIVATIVES AS A mTOR/PI3K SUPPRESSOR
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Paragraph 0079; 0080, (2016/10/08)
The invention discloses pyrido[1,2-a]pyrimidone derivatives as a mTOR/PI3K suppressor; and in particular, this invention relates to a compound having the formula (I) structure or its pharmaceutically acceptable salts.
