cas 67443-38-3, 5-Bromo-2-chloro-3-nitropyridine

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Alkylsulfonamide-containing quinazoline derivatives as potent and orally bioavailable PI3Ks inhibitors
Phosphoinositide 3-kinases (PI3Ks) are regarded as promising targets for treatment of various cancers due to their roles in regulating cell proliferation, differentiation, migration, and survival. Here we report our efforts to develop potent and orally bioavailable PI3K inhibitors for the treatment of cancers. The alkylsulfonamide-containing quinazoline derivatives A1–A18 significantly inhibited PI3Kα, and cell proliferation among HCT-116, MCF-7 and SU-DHL-6 cell lines. The optimal compound A1 displayed potent inhibitory activity against PI3Kα (IC50 = 4.5 nM), PI3Kβ (IC50 = 4.5 nM), PI3Kγ (IC50 = 4.5 nM), PI3Kδ (IC50 = 4.5 nM) and significantly inhibited the growth of HCT-116, MCF-7 and SU-DHL-6 cell lines with IC50 values of 0.82 μM, 0.99 μM and 0.19 μM, respectively. Western blot analysis demonstrated A1 significantly suppressed the phosphorylation of AKTS473 in a dose-dependent manner. Furthermore, A1 could markedly inhibit cancer growth at the dose of 25 mg/kg in nude mouse HCT-116 xenograft model in vivo without causing significant weight loss or toxicity.
Hei, Yuan-Yuan,Zhang, San-Qi,Feng, Yifan,Wang, Jin,Duan, Weiming,Zhang, Hao,Mao, Shuai,Sun, Haopeng,Xin, Minhang
(2019/06/08)

New tetracyclic 1,4-oxazepines constructed via practically simple tandem condensation strategy from readily available synthons
A streamlined synthetic methodology towards novel tetracyclic 1,4-oxazepines from readily available precursors is described. The compounds, designed as more soluble version of the earlier described, poorly soluble dibenzo[b,f][1,4]oxazepines, were obtained in high yields and as a single regioisomer as a result of three tandem chemical events - nucleophilic aromatic substitution, Smiles rearrangement and denitrocyclization.
Sapegin, Alexander V.,Kalinin, Stanislav A.,Smirnov, Alexey V.,Dorogov, Mikhail V.,Krasavin, Mikhail
p. 1077 - 1083
(2014/01/23)

Large-scale solvent-free chlorination of hydroxy-pyrimidines,-pyridines,- pyrazines and-amides using equimolar POCl3
Chlorination with equimolar POCl3 can be efficiently achieved not only for hydroxypyrimidines, but also for many other substrates such as 2-hydroxy-pyridines,-quinoxalines, or even-amides. The procedure is solvent-free and involves heating in a sealed reactor at high temperatures using one equivalent of pyridine as base. It is suitable for large scale (multigram) batch preparations.
Wang, Han,Wen, Kun,Wang, Le,Xiang, Ye,Xu, Xiaocheng,Shen, Yongjia,Sun, Zhihua
experimental part
p. 4533 - 4544
(2012/06/30)

[11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers
GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [11C]GSK2126458 and [18F]GSK212 6458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 20-30% decay corrected radiochemical yield, and 370-740 and 37-222 GBq/lmol specific activity at end of bombardment (EOB), respectively.
Wang, Min,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
experimental part
p. 1569 - 1574
(2012/04/04)

NOVEL PYRIDOPYRIMIDINE DERIVATIVES AND USE THEREOF
The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.
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Page/Page column 17

(2012/09/25)

HISTAMINE H3 INVERSE AGONISTS AND ANTAGONISTS AND METHODS OF USE THEREOF
Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.
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Page/Page column 117

(2010/08/18)

New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors
This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.
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Page/Page column 46

(2009/10/21)

New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors
This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.
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Page/Page column 29

(2009/12/04)

Practical synthesis of a potent bradykinin B1 antagonist via enantioselective hydrogenation of a pyridyl N-acyl enamide
(Chemical Equation Presented) A practical and efficient synthesis of bradykinin B1 antagonist 1 is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of 1 in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.
O'Shea, Paul D.,Gauvreau, Danny,Gosselin, Francis,Hughes, Greg,Nadeau, Christian,Roy, Amelie,Shultz, C. Scott
body text
p. 4547 - 4553
(2009/09/30)

THIAZOLE DERIVATIVES AND THEIR USE AS ANTI-TUMOUR AGENTS
The invention concerns thiazole derivatives of Formula (I) or pharmaceutically-acceptable salts thereof, wherein each of R, Ring A, m, R1, R2 and R3 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of disease mediated by a PI3K enzyme and/or a mTOR kinase.
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Page/Page column 77

(2008/06/13)

SULFONYL BENZIMIDAZOLE DERIVATIVES
This invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein A, R1, R2 ,R3, R4, R5, m and n are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity such as, but not limited to, inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, acute cerebral ischemia, pain, chronic pain, acute pain, post herpetic neuralgia, neuropathies, neuralgia, diabetic neuropathy, HIV-related neuropathy, nerve injury, rheumatoid arthritic pain, osteoarthritic pain, back pain, cancer pain, dental pain, fibromyalgia, neuritis, sciatica, inflammation, neurodegenerative disease, cough, broncho constriction, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colitis, cerebrovascular ischemia, emesis such as cancer chemotherapy-induced emesis, rheumatoid arthritis, asthma, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, GERD, constipation, diarrhea, functional gastrointestinal disorders, irritable bowel syndrome, cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, COPD, cryptogenic fibrosing alveolitis and bronchitis.
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Page/Page column 45

(2008/06/13)

BICYCLIC HETEROCYCLES HYDROXAMATE COMPOUNDS USEFUL AS HISTONE DEACETYLASE (HDAC) INHIBITORS
The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to heterocyclic containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase (HDAC) activities.
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Page/Page column 56

(2010/11/24)

Sulfonyl benzimidazole derivatives
This invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein A, B, R1, R2 and R3 are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity such as, but not limited to, inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, acute cerebral ischemia, pain, chronic pain, acute pain, post herpetic neuralgia, neuropathies, neuralgia, diabetic neuropathy, HIV-related neuropathy, nerve injury, rheumatoid arthritic pain, osteoarthritic pain, back pain, cancer pain, dental pain, fibromyalgia, neuritis, sciatica, inflammation, neurodegenerative disease, cough, broncho constriction, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colitis, cerebrovascular ischemia, emesis such as cancer chemotherapy-induced emesis, rheumatoid arthritis, asthma, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, GERD, constipation, diarrhea, functional gastrointestinal disorders, irritable bowel syndrome, cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, COPD, cryptogenic fibrosing alveolitis and bronchitis.
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Page/Page column 55

(2008/06/13)

5-HETEROARYL THIAZOLES AND THEIR USE AS P13K INHIBITORS
The invention provides thiazole derivatives of formula (I), or pharmaceutically acceptable salts thereof in which Ring A, R1, R2 and R3 are as defined in the specification; a processes for their preparation; pharmaceutical compositions containing them; and their use in therapy, for example in the treatment of disease mediated by a PI3K enzyme and/or a mTOR kinase.
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Page/Page column 95

(2010/11/30)

PYRROLOPYRIDINE DERIVATIVES
The present invention relates to novel pyrrolopyridine derivatives, pharmaceutical compositions containing these compounds and their use in the treatment of diseases, particularly pain, which diseases are caused directly or indirectly by an increase or decrease in activity of the cannabinoid receptor.
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Page/Page column 28-29

(2008/06/13)

Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides
This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with new piperidine 4-alkenyl derivatives that possess unique antiviral activity. More particularly, the present invention relates to compounds useful for the treatment of HIV and AIDS. The compounds of the invention for the general Formula I: wherein: Z is Q is selected from the group consisting of: —W— is
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Page/Page column 31; 32

(2010/02/06)

1,4-Disubstituted benzo-fused urea compounds
Disclosed are compounds of the formulas (I) and (II) shown below which are active as anti-inflammatory agents. Also disclosed are methods of using and making such compounds. wherein G, X, A and Q are described herein.
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(2008/06/13)

IMIDAZO-PYRIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
The present invention is directed to 3-phenylimidazol[4,5-b]pyridine derivatives, that are selective ligands for GABAA receptors. These compounds are useful in the treatment and prevention of disorders of the central nervous system, including anxiety and convulsions.
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Page/Page column 13

(2008/06/13)

Oxidative cyclization of N-methyl- and N-benzoylpyridylthioureas. Preparation of new thiazolo[4,5-b] and [5,4-b]pyridine derivatives
Cyclization of N-methyl- and N-benzoylpyridylthioureas, prepared from the corresponding aminopyridines, has been realized using various conditions. With bromine in acetic acid or potassium ferricyanide, the cyclization occurred on the nitrogen of the pyridine ring and pyridinium salts or 1,2,4-thiadiazolo[2,3-a]pyridylidene systems were obtained. On the other hand, treatment of the thioureas with sodium methoxide in N-methylpyrrolidinone (NMP) led to formation of thiazolo[4,5-b] and [5,4-b]pyridines, which are interesting targets for biological evaluation.
Jouve, Karine,Bergman, Jan
p. 261 - 268
(2007/10/03)

Angiogenesis inhibitors
The present invention relates to compounds which inhibit tyrosine kinase enzymes, compositions which contain tyrosine kinase inhibiting compounds and methods of using tyrosine kinase inhibitors to treat tryrosine kinase-dependent diseases/conditions such as angiogenenesis, cancer, atherosclerosis, diabetic retinopathy or autoimmune diseases, in mammals.
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(2008/06/13)

Antithrombotic quinoxazolines
Quinoxazolines having antithrombotic activity. Exemplary of those disclosed are: 4-{[6-(N-carboxymethyl-quinolin-8-yl-sulphonylamino)-1-methyl-2-oxo-1,2-dihydroquinoxalin-3-yl]-methyl}-benzamidine, 4-{[6-(1-(N-cyclopentyl-carboxymethylcarbonylamino)-cyclo-propyl)-1-methyl-2-oxo-1,2-dihydroquinoxalin-3-yl]-methyl}-benzamidine, and 4-{[7-(N-carboxymethylaminocarbonyl-ethylamino)-4-methyl-quinolin-2-yl]-oxo}-benzamidine.
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(2008/06/13)

Tyrosine kinase inhibitors
The present invention relates to benzinidazole compounds which inhibit tyrosine kinase enzymes, compositions which contain tyrosine kinase inhibiting compounds and methods of using tyrosine kinase inhibitors to treat tyrosine kinase-dependent diseases/conditions such as angiogenenesis, cancer, atherosclerosis, diabetic retinopathy or autoimmune diseases, in mammals.
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(2008/06/13)

2-(3-AMINO-5-HALO-2-PYRIDYLALKYLAMINO)-PYRIMIDONES USEFUL AS HISTAMINE H1-ANTAGONISTS
The invention describes 5-halo-3-amino-2-pyridyl derivatives which are useful as histamine H 1-antagonists. Particular compounds described are 2-4-(5-bromo-3-aminopyrid-2-yl)butylamino!-5-(6-methylpyrid-3-ylmethyl)-4-pyr imidone and 2-4-(5-bromo-3-aminopyrid-2-yl)butylamino!-5-(N-oxopyrid-4-ylmethyl)-4-pyrimi done.
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(2008/06/13)

3,5-Substituted-2-pyridylalkylamino compounds having histamine H1 -antagonist activity
3,5-Substituted-2-pyridylalkylamino derivatives are disclosed which are useful as histamine H1 -antagonists.
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(2008/06/13)

2-(3,5-SUBSTITUTED-2-PYRIDYLALKYLAMINO)-5-OXOPYRIDYLMETHYL-4-PYRIMIDONES USEFUL AS HISTAMINE H1-ANTAGONISTS
Pyridone derivatives useful as histamine H 1-antagonists are disclosed.
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(2008/06/13)

2-(3,5-SUBSTITUTED-2-PYRIDYLALKYLAMINO)-5-BENZYL-4-PYRIMIDONES
3,5-Disubstituted-2-pyridylalkylamino-5-optionally substituted benzyl-4-pyrimidones having histamine H 1-antagonist activity are disclosed.
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(2008/06/13)

REACTIVITIES OF HETEROCYCLIC COMPOUNDS IN NITRATION. 5. KINETICS OF NITRATION OF 5-SUBSTITUTED 2-PICRYLAMINOPYRIDINES
The kinetics of nitration of 5-bromo-, 5-chloro-, and 5-nitro-2-picrylaminopyridines in 80-96percent sulfuric acid were studied by a spectrophotometric method.The kinetic parameters of nitration were calculated.The UV spectra of the neutral and protonated forms in aqueous sulfuric acid solutions were identified.It was established that the indicated compounds are nitrated in the protonated form.The relative (as compared with benzene) rates of nitration were calculated.
Sharnin, G. P.,Falyakhov, I. F.,Khairutdinov, F. G.
p. 1234 - 1238
(2007/10/02)