- Synthesis of Pyridazine-Based α-Helix Mimetics
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A versatile synthesis of pyridazine-based small molecule α-helix mimetics (A) is presented. Modular C-C, C-N, and C-O bond-forming reactions allow for the inclusion of a variety of aliphatic, basic, aromatic, and heteroaromatic side chain moieties. This robust synthesis is suitable for the preparation of small pyridazine-based libraries.
- Londregan, Allyn T.,Piotrowski, David W.,Wei, Liuqing
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Read Online
- Heterocyclic compound as well as pharmaceutical composition, preparation method, intermediate and application thereof
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The invention discloses a heterocyclic compound as well as a pharmaceutical composition, a preparation method, an intermediate and application thereof. The structure of the heterocyclic compound is shown as a formula I, and the heterocyclic compound has CDK7 inhibitory activity and can be used for treating diseases such as tumors.
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Paragraph 0394-0398
(2021/06/23)
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- TYK2 INHIBITORS AND USES THEREOF
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Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.
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Paragraph 00269; 00282
(2020/09/27)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 0380-0381; 0384-0385
(2020/08/05)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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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.
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Page/Page column 162; 163
(2020/05/15)
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- PROCESS FOR THE PREPRATION OF 7-(4,7-DIAZASPIRO[2.5]OCTAN-7-YL)-2-(2,8-DIMETHYLIMIDAZO[1,2-B]PYRIDAZIN-6-YL)PYRIDO[1,2-A]PYRIMIDIN-4-ONE DERIVATIVES
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The present invention relates to a process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[l,2- b]pyridazin-6-yl)pyrido[l,2-a]pyrimidin-4-one derivatives useful pharmaceutically active compounds.
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Page/Page column 54-55
(2019/04/16)
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- PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
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Page/Page column 56
(2019/11/12)
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- Design and Evaluation of Heterobivalent PAR1-PAR2 Ligands as Antagonists of Calcium Mobilization
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A novel class of bivalent ligands targeting putative protease-activated receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1-PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders.
- Majewski, Mark W.,Gandhi, Disha M.,Rosas, Ricardo,Kodali, Revathi,Arnold, Leggy A.,Dockendorff, Chris
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supporting information
p. 121 - 126
(2019/01/04)
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- CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS
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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.
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Paragraph 0200
(2019/07/14)
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- COMPOUNDS FOR TREATING HUNTINGTON'S DISEASE
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The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease. In particular, the present description relates to substituted bicyclic heteroaryl compounds of Formula (I), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.
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Page/Page column 184; 185
(2019/01/06)
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- 6,7-DIAZAINDAZOLE AND 6,7-DIAZAINDOLE DERIVATIVES AND USE IN TREATMENT, AMELIORATION OR PREVENTION OF INFLUENZA THEREOF
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Provided herein is a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameliorating or preventing influenza.
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Page/Page column 50-51
(2017/09/02)
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- PYRIMIDINE AND PYRIDINE DERIVATIVES AND USE IN TREATMENT, AMELIORATION OR PREVENTION OF INFLUENZA THEREOF
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Provided herein is a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameliorating or preventing influenza.
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Page/Page column 170
(2017/12/28)
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- BIARYL KINASE INHIBITORS
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The present disclosure is directed to biaryl compounds of formula (I) which can inhibit AAKl (adaptor associated kinase 1), compositions comprising such compounds and their use for treating e.g. pain, Alzheimer's disease, Parkinson's disease and schizophrenia.
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Page/Page column 216
(2017/07/31)
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- CK2 INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. For Formula (I) compounds R1, R2, R3, Ar and Z are as defined in the specification. The inventive Formula (I) compounds are inhibitors of CK2 and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer, inflammation and immunological disorders.
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Paragraph 0454; 0456
(2018/02/01)
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- Synthesis method of 4-bromine-6-chloropyridazine-3(2H)ketone
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The invention relates to a synthesis method of 4-bromine-6-chloropyridazine-3(2H)ketone. The synthesis method of the 4-bromine-6-chloropyridazine-3(2H)ketone comprises the following steps: continuously conducting reaction in a proper solvent and under the action of alkali at 0 to 100 DEG C for 6 to 25 hours by taking 3-amino-6-chloropyridazine, liquid bromine, concentrated sulfuric acid and sodium nitrite as raw materials to produce a 4-bromine-6-chloropyridazine-3(2H)ketone crude product, wherein the ratio of the 3-amino-6-chloropyridazine to the liquid bromine is 1:(0.8-3.2), and the ratio of the 3-amino-6-chloropyridazine to the sodium nitrite is 1:(1.0-2.1); performing purification to obtain a 4-bromine-6-chloropyridazine-3(2H)ketone pure product. According to the synthesis method of the 4-bromine-6-chloropyridazine-3(2H)ketone, the raw materials are easily available and the price is reasonable; meanwhile, heavy metal and corrosive gas are not used in the preparation reaction, the reaction is mild, special requirements on the reaction equipment are not needed, and the common corrosion-resistant equipment can perform production; in addition, the reaction condition is moderate.
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Paragraph 0012; 0013; 0014; 0015; 0016; 0017; 0018
(2017/08/28)
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- Synthesis method of 6-cholro-8-bromoimidazole[1,2-b]pyridazine
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The invention relates to a synthesis method of 6-chloro-8-bromoimidazole[1,2-b]pyridazine. 3-amino-6-chloropyridazine, liquid bromine, and a chloroacetaldehyde water solution are taken as the raw materials, the ratio of amount of substance of 3-amino-6-chloropyridazine to liquid bromine is 1:1.0-4.5, the ratio of amount of substance of 3-amino-6-chloropyridazine to the chloroacetaldehyde water solution (40%) is 5:1.0-1:3.2; in a proper solvent, in the presence of alkali, raw materials carry out continuous reactions at a temperature of 50 to 100 DEG C to generate a coarse product of 6-cholro-8-bromoimidazole[1,2-b]pyridazine, and then the coarse product is purified to obtain purified product of 6-cholro-8-bromoimidazole[1,2-b]pyridazine. The provided synthesis method has the advantages that the raw materials are easily available, the prices are reasonable, at the same time, no heavy metal or corrosive gas is used in the preparation reactions, the reactions are mild, there is no special requirement on reaction equipment, the product can be produced by common corrosion resistant equipment, and the reaction conditions are moderate.
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Paragraph 0027
(2017/01/02)
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- INHIBITORS OF PHOSPHODIESTERASE 10 ENZYME
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The present invention relates to novel imidazo[1,2-b]pyridazine and imidazo[1,2-a]-pyrazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which may be useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.
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Paragraph 0155; 0156; 0157
(2015/07/27)
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- INHIBITORS OF PHOSPHODIESTERASE 10 ENZYME
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The present invention relates to novel imidazo[1,2-b]pyridazine and imidazo[1,2-a]-pyrazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which may be useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.
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Page/Page column 29
(2014/02/15)
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- BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS
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The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.
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Paragraph 0215; 0216
(2014/09/29)
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- IMIDAZOPYRIDAZINE COMPOUNDS
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The present invention relates to the use of novel compounds of formula I: wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.
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Paragraph 0225-0226
(2013/05/09)
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- IMIDAZOPYRIDAZINE COMPOUNDS
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The present invention relates to the use of novel compounds of formula (I): wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 50-51
(2013/05/22)
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- A short and straightforward approach towards 6-amino and 6-aminoalkyl thiazolo[4,5-c]pyridazines
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A facile and efficient synthesis of 6-amino and 6-aminoalkyl thiazolo[4,5-c]pyridazines is reported. The key step for the construction of this novel bicyclic scaffold was the reaction between 3-amino-4-bromopyridazine derivatives and alkylisothiocyanates.
- Stella, Alessandro,De Jonghe, Steven,Segers, Kenneth,Herdewijn, Piet
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supporting information
p. 830 - 833
(2013/02/25)
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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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 d
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Page/Page column 74
(2013/05/09)
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- Isoxazolines as Therapeutic Agents
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The present invention provides compound of Formula (I) biologically active metabolites, pro-drugs, isomers, stereoisomers, solvates, hydrates and pharmaceutically acceptable salts thereof wherein the variables are defined herein. The compounds of the invention are useful for treating immunological conditions.
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Paragraph 0885-0886
(2013/03/26)
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- TRICYCLIC HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS
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There is provided compounds of formula (I), wherein R1, R2, X, R3 and R4 have meanings given in the description (and which compounds are optionally substituted as indicated in the description), and pharmaceutica
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Page/Page column 71
(2013/03/26)
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- Rational design of highly selective spleen tyrosine kinase inhibitors
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A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is described. Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis, and SLE. Fostamatinib, a Syk inhibitor that successfully completed phase II clinical trials, also exhibits some undesirable side effects. More selective Syk inhibitors could offer safer, alternative treatments. Through a systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk ATP binding site as a rare combination among sequence aligned kinases and hypothesized that optimizing the interaction between them and a Syk inhibitor molecule would impart high selectivity for Syk over other kinases. We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our hypothesis and offer useful guidance to other researchers in the field.
- Lucas, Matthew C.,Goldstein, David M.,Hermann, Johannes C.,Kuglstatter, Andreas,Liu, Wenjian,Luk, Kin Chun,Padilla, Fernando,Slade, Michelle,Villase?or, Armando G.,Wanner, Jutta,Xie, Wenwei,Zhang, Xiaohu,Liao, Cheng
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supporting information
p. 10414 - 10423
(2013/02/22)
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- SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS AS KINASE INHIBITOR COMPOUNDS
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The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against c-Met and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
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Page/Page column 28-29
(2012/04/23)
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- SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS
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The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against ALK and are useful in treating disorders related to abnormal protein kinase activities such as cancer, neurological and psychiatric diseases
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Page/Page column 36
(2012/04/23)
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.
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Page/Page column 80
(2012/05/21)
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- IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AND THEIR USE AS PDE10 INHIBITORS
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The present invention relates to novel imidazo[1,2-b]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.
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Page/Page column 67
(2011/05/11)
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- IMIDAZOPYRIDIN-2-ONE DERIVATIVES
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A compound represented by formula (I) having mTOR inhibitory activity or a pharmacologically acceptable salt thereof.
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Page/Page column 59
(2011/04/24)
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- IMIDAZOPYRIDAZINYL COMPOUNDS AND THEIR USES FOR CANCER
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Disclosed are imidazopyridazinyl compounds of Formula (I): (I), or pharmaceutically salts and prodrugs thereof, wherein R3 is C2-4alkenyl or a cyclic group, and R1 and R2 are defined herein. Also disclosed are methods of using such compounds in the treatment of at least one CYP17 associated condition, such as, for example, cancer, and pharmaceutical compositions comprising such compounds.
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Page/Page column 29-30
(2011/11/13)
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- IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AND THEIR USE AS PDE10 INHIBITORS
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The present invention relates to novel imidazo[1,2-b]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.
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Page/Page column 28
(2011/11/12)
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- FUSED BICYCLIC KINASE INHIBITORS
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Compounds of Formula I, as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as but not limited to tumors driven at least in part by at least one of RON, MET, IR, IGF-1 R, or ALK. This Abstract is not limiting of the invention.
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Page/Page column 59
(2011/12/02)
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- IMIDAZOPYRIDAZINECARBONITRILES USEFUL AS KINASE INHIBITORS
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The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) imidazopyridazines inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 114-115
(2010/04/28)
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- HETEROCYCLIC MODULATORS OF GPR119 FOR TREATMENT OF DISEASE
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Disclosed herein are compounds and methods which may be useful as inhibitors of GPRl 19 for the treatment or prevention of diseases including cardiovascular and metabolic diseases.
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Page/Page column 90-91
(2010/08/09)
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- Inhibitors of Bruton's Tyrosine Kinase
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This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formulae I-III: wherein, variables Q, R, X, X′, Y1, Y2, Y2′, Y3, Y4, Y5, m, and n are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formulae I-III and at least one carrier, diluent or excipient.
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Page/Page column 93
(2010/09/07)
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- SUBSTITUTED IMIDAZOPYRIDAZINES USEFUL AS KINASE INHIBITORS
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The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I imidazopyridazines inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 44-45
(2009/10/09)
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- NOVEL PYRIDINONES AND PYRIDAZINONES
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This application discloses 5-phenyl-1H-pyridin-2-one and 6-phenyl-2H-pyridazin-3-one deriva-tives according to generic Formulae I-III : wherein, variables R, X, Y1, Y2, Y3, Y4, n and m are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat in-flammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formulae I-III and at least one carrier, diluent or excipient.
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Page/Page column 68
(2009/10/09)
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- SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS AS KINASE INHIBITOR COMPOUNDS
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Pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
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Page/Page column 33
(2010/01/12)
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- KINASE INHIBITOR COMPOUNDS
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Pyridine and pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
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Page/Page column 32
(2008/12/07)
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- Fused heterocyclic compounds useful as kinase modulators
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Compounds having the formula (1), and enantiomers, and diastereomers, pharmaceutically-acceptable salts, thereof, are usefuil as kinase modulators, including MK2 modulation, wherein one of E and F is a nitrogen atom and the other of E and F is a carbon atom, Z is N or CR3, and R1, R2, R3, X and Y are as defined herein.
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Page/Page column 27
(2010/11/26)
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- FUSED HETEROCYCLES AS LCK INHIBITORS
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There is provided fused heterocycles of imidazopyridazine or pyrazolopyrimidine derivative represented by the formula (I), which have excellent Lck inhibitory activity and are useful for a medicament particularly an immunosuppressive agent. [wherein one of Y and Z is C atom, and the other is N atom; -X-10 is -N (R1) - or the like, -R1 is hydrogen or the like, -A- is bond or the like, is cycloalkyl, aryl or the like, -E- is bond or the like, -R3 is aryl, aromatic heterocycle or the like, -R4, -R5 and -R6 are the same or different, each being hydrogen or the like.]
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Page/Page column 43
(2010/11/25)
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- BICYCLIC NITROGENOUS FUSED-RING COMPOUND
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The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula or a salt thereof. Wherein R1 denotes a hyd
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Page/Page column 35-36
(2008/06/13)
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