- SUBSTITUTED (AZA)INDOLE DERIVATIVES
-
The invention relates to substituted (aza)indole derivatives, or pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof, as well as to pharmaceutical compositions containing them and to their use as modulators of α7 nicotinic acetylcholine receptor activity in a mammalian subject. (I)
- -
-
Page/Page column 82
(2020/02/06)
-
- Preparation method for 5-bromo-7-azindole
-
The invention belongs to the technical field of preparation of 5-bromo-7-azindole, in particular to a preparation method for the 5-bromo-7-azindole. The method comprises the following steps: taking 2-amino-5-bromopyridine as a raw material, and performing the steps in sequence: (1) introducing iodine through an iodine reagent; (2) performing a coupling reaction with methylbutynol; and (3) performing a ring-closing reaction under the catalysis of inorganic strong base to prepare the 5-bromo-7-azindole, wherein the catalyst adopted in the coupling reaction in the step (2) is bis(benzonitrile)palladium dichloride or [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex compound. According to the preparation method, cheap 2-amino-5-bromopyridine is taken as the rawmaterial in the step (1); the catalyst with high catalyzing efficiency and a solvent which is easy to treat are adopted; purifying steps in each step are simple; the yield is high; and the and the yield of the finally prepared product, namely, the 5-bromo-7-azindole, can reach over 93 percent.
- -
-
Page/Page column 5-7
(2019/04/17)
-
- TAM family kinase and/or CSF1R kinase inhibitor and application thereof
-
The invention provides a novel inhibitor compound shown in a general formula (I). The compound has good kinase inhibition activity and can be used for preventing and/or treating diseases mediated by abnormal expression of TAM family kinase and/or a ligand thereof. The compound can target CSF1R kinase and can be used for preventing and/or treating diseases mediated by abnormal expression of a TAM family kinase receptor and/or a CSF1R kinase receptor and/or ligands thereof.
- -
-
Paragraph 0707; 0711-0713
(2019/08/06)
-
- 2 - Amino -3 - iodo -5 - bromo pyridine synthesis method
-
The invention relates to a method for synthesizing 2-amino-3-iodo-5-bromopyridine. The method comprises the steps of enabling 2-amino-5-bromopyridine and N-iodo succinimide, which serve as raw materials and are in the mass ratio of 1: (1.7-3.5), to react at the temperature of 23-115 DEG C in a proper solvent so as to produce 2-amino-3-iodo-5-bromopyridine, and purifying, thereby obtaining a pure product 2-amino-3-iodo-5-bromopyridine. According to the method, the raw materials are relatively easily obtained and are reasonable in price; meanwhile, during preparation reaction, no heavy metal and corrosive gas are used, the reaction is mild, no special requirements on reaction equipment is required, and ordinary corrosion-resistant equipment can be applied to production; in addition, reaction conditions of the method are moderate.
- -
-
Paragraph 0017-0027; 0029-0032
(2018/09/08)
-
- [1,2,4]TRIAZOLO[1,5-A]PYRIDINYL SUBSTITUTED INDOLE COMPOUNDS
-
Disclosed are compounds of Formula (I) or a salt thereof, wherein R1, R2, R3, R4, R5, m, n, and p are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.
- -
-
Page/Page column 154; 155
(2018/02/28)
-
- Synthesis and evaluation of the anticoccidial activity of trifluoropyrido[1,2-a]pyrimidin-2-one derivatives
-
Screening of our chemical library to discover new molecules exhibiting in vitro activity against the invasion of host cells by Eimeria tenella revealed a lead compound with an IC50 of 15 μM. Structure-activity relationship studies were conducted with 34 newly synthesized compounds to identify more active molecules and enhance in vitro activity against the parasite. Four compounds were more effective in inhibiting MDBK cell invasion in vitro than the lead compound.
- Silpa, Laurence,Niepceron, Alisson,Laurent, Fabrice,Brossier, Fabien,Pénichon, Mélanie,Enguehard-Gueiffier, Cécile,Abarbri, Mohamed,Silvestre, Anne,Petrignet, Julien
-
supporting information
p. 114 - 120
(2015/12/18)
-
- Carbon-14 radiolabeling and tissue distribution evaluation of MMV390048
-
The antimalarial compound MMV390048 ([14C]-11) was labeled with carbon-14 isotope via a 3-step synthesis. It was obtained in a 15.5% radiochemical overall yield from carbon-14 labeled methyl iodide with a radiochemical purity of >99%. After single oral administration of [14C]-11 to albino and pigmented rats its tissue distribution profile was studied. Tissue distribution results showed high local exposure in the GI tract and excretory organs but low exposure of all other tissues. The radioactivity uptake was higher in the eyes of the pigmented rats than in the eyes of the albino rats at all-time points. The highest accumulation reached in the eyes of the pigmented rats was 0.46% at 6?hours. However, these levels are still very low as compared to the other organs studied. There was very little radioactivity from MMV390048 ([14C]-11) present in the skin of both the albino and pigmented rats. The results obtained are supportive of further development of MMV390048 as a potential antimalarial compound.
- Sonopo, Molahlehi S.,Pillay, Adushan,Chibale, Kelly,Marjanovic-Painter, Biljana,Donini, Cristina,Zeevaart, Jan R.
-
p. 680 - 688
(2016/12/26)
-
- Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites
-
The synthesis of 2,3,5-trisubstituted 7-azaindoles as well as 2,5-disubstituted 7-azaindoles from 3,5-dihalogenated 2-aminopyridines is outlined. Using a double Sonogashira coupling reaction on 2-amino-3,5-diiodopyridine followed by the Cacchi reaction the synthesis of 2,3,5-trisubstituted 7-azaindoles was accomplished. In addition, using two sequential Sonogashira coupling reactions on 2-amino-5-bromo-3-iodopyridine and a potassium t-butoxide mediated ring closure reaction resulted in the assembly of 2,5-disubstituted 7-azaindoles. The 5-alkynyl substituent of the azaindole was easily converted into both quinoxaline and triazole substituents, the latter utilizing an alkyne-azide cycloaddition reaction. Some of these azaindole derivatives showed very promising biological activity against the gastrointestinal protozoal parasite Giardia duodenalis.
- Leboho, Tlabo C.,Giri, Somnath,Popova, Inessa,Cock, Ian,Michael, Joseph P.,De Koning, Charles B.
-
p. 4943 - 4951
(2015/08/03)
-
- 1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
-
The present invention relates to novel antiproliferative1H-1, 8-naphthyridin-2-ones of the general formula (I) or pharmaceutically acceptable salts thereof: In which the variable groups are as defined herein, and their preparation and use in therapeutic treatment of disorders related to inhibition of tyrosine kinases in warm blooded animals. The compounds can overcome imatinib induced drug resistance.
- -
-
Page/Page column 15
(2015/12/30)
-
- ANTIBACTERIAL COMPOUNDS
-
The present disclosure relates to a novel combination of compounds, their use as antibacterials, compositions comprising them and methods for treating or preventing bacterial infections, more particularly, bacterial infections caused by Gram-negative pathogens and/or drug resistant Gram-negative bacteria.
- -
-
Paragraph 0246; 0247
(2015/09/22)
-
- The acid-catalysed synthesis of 7-azaindoles from 3-alkynyl-2- aminopyridines and their antimicrobial activity
-
The synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines using acidic conditions, namely, a mixture of trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA), is described. This methodology resulted in the synthesis of fifteen 7-azaindoles, with most containing substituents at the 2- and 5-positions. The majority of these were tested for antimicrobial activity against a range of bacteria and yeasts. The 7-azaindoles displayed the best activity against the yeasts, particularly against Cryptococcus neoformans, where activities as low as 3.9 μg ml-1 were observed.
- Leboho, Tlabo C.,Van Vuuren, Sandy F.,Michael, Joseph P.,De Koning, Charles B.
-
p. 307 - 315
(2014/01/06)
-
- Concise syntheses of meridianins and meriolins using a catalytic domino amino-palladation reaction
-
A synthesis of natural and synthetic members of the meridianin family of kinase inhibitory natural products has been developed. The sequence utilizes a variation of the Cacchi palladium-catalyzed domino reaction to efficiently construct the heterocyclic f
- Walker, Scott R.,Czyz, Milena L.,Morris, Jonathan C.
-
supporting information
p. 708 - 711
(2014/03/21)
-
- Full functionalization of the 7-azaindole scaffold by selective metalation and sulfoxide/magnesium exchange
-
Filling positions: 7-Azaindoles are important targets in the pharmaceutical industry. All five carbon positions of the azaindole ring system can be functionalized in a predictable manner starting from the appropriately substituted azaindole 1 by directed metalation and halogen/magnesium and sulfoxide/magnesium exchange. The products are fully substituted azaindoles of type 2.
- Barl, Nadja M.,Sansiaume-Dagousset, Elodie,Karaghiosoff, Konstantin,Knochel, Paul
-
supporting information
p. 10093 - 10096
(2013/10/01)
-
- Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst
-
This paper describes the preparation of indoles, azaindoles and benzofurans in pure water by using a new heterogeneous Pd-Cu/C catalyst through a cascade Sonogashira alkynylation-cyclization sequence. Details of the optimization studies and the substrate scope are discussed. This procedure allows the preparation of heterocycles with good yields and is tolerant to a wide variety of functional groups.
- Rossy, Cybille,Fouquet, Eric,Felpin, Francois-Xavier
-
supporting information
p. 1426 - 1431
(2013/08/23)
-
- Structure-activity-relationship studies around the 2-amino group and pyridine core of antimalarial 3,5-diarylaminopyridines lead to a novel series of pyrazine analogues with oral in vivo activity
-
Replacement of the pyridine core of antimalarial 3,5-diaryl-2- aminopyridines led to the identification of a novel series of pyrazine analogues with potent oral antimalarial activity. However, other changes to the pyridine core and replacement or substitution of the 2-amino group led to loss of antimalarial activity. The 3,5-diaryl-2-aminopyrazine series showed impressive in vitro antiplasmodial activity against the K1 (multidrug resistant) and NF54 (sensitive) strains of Plasmodium falciparum in the nanomolar IC50 range of 6-94 nM while also demonstrating good in vitro metabolic stability in human liver microsomes. In the Plasmodium berghei mouse model, this series generally exhibited good efficacy at low oral doses. One of the frontrunner compounds, 4, displayed potent in vitro antiplasmodial activity with IC 50 values of 8.4 and 10 nM against the K1 and NF54 strains, respectively. When evaluated in P. berghei-infected mice, compound 4 was completely curative at an oral dose of 4 × 10 mg/kg.
- Younis, Yassir,Douelle, Frederic,González Cabrera, Diego,Le Manach, Claire,Nchinda, Aloysius T.,Paquet, Tanya,Street, Leslie J.,White, Karen L.,Zabiulla, K. Mohammed,Joseph, Jayan T.,Bashyam, Sridevi,Waterson, David,Witty, Michael J.,Wittlin, Sergio,Charman, Susan A.,Chibale, Kelly
-
p. 8860 - 8871
(2013/12/04)
-
- NOVEL PROCESSES FOR THE MANUFACTURE OF PROPANE-1-SULFONIC ACID {3-[5-(4-CHLORO-PHENYL)-1H-PYRROLO[2,3-B]PYRIDINE-3-CARBONYL]-2,4-DIFLUORO-PHENYL}-AMIDE
-
According to the present invention there are provided novel processes for the manufacture of the compound of formula (1) as well as novel synthesis routes for key intermediates used in those processes.
- -
-
Page/Page column 28
(2012/02/05)
-
- Novel Processes for the manufacture of Propane-1-sulfonic acid -amide
-
According to the present invention there are provided novel processes for the manufacture of the compound of formula 1 as well as intermediates and novel synthesis routes for key intermediates used in those processes.
- -
-
Page/Page column 13-14
(2012/02/03)
-
- Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile (Perampanel): A novel, noncompetitive α-amino-3-hydroxy-5- methyl-4-isoxazolepropanoic acid (AMPA) receptor antagonist
-
Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5- pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (perampanel, 6), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.
- Hibi, Shigeki,Ueno, Koshi,Nagato, Satoshi,Kawano, Koki,Ito, Koichi,Norimine, Yoshihiko,Takenaka, Osamu,Hanada, Takahisa,Yonaga, Masahiro
-
p. 10584 - 10600
(2013/02/23)
-
- 7, 9-NITROGEN RADICAL-4-OXO-4H-PYRIDO[L,2-A]PYRIMIDINE-2-CARBOXYLIC ACID BENZYLAMIDE ANTI-VIRALS
-
The present invention provides a compound of Formula I or a pharmaceutically acceptable derivative, salt or prodrug thereof. Further provided is a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of Formula I or a pharmaceutically acceptable derivative, salt or prodrug thereof. A pharmaceutical composition or medicament comprising a compound of Formula I is also provided
- -
-
Page/Page column 24
(2012/02/02)
-
- Structure-activity relationship studies of orally active antimalarial 3,5-substituted 2-aminopyridines
-
In an effort to address potential cardiotoxicity liabilities identified with earlier frontrunner compounds, a number of new 3,5-diaryl-2-aminopyridine derivatives were synthesized. Several compounds exhibited potent antiplasmodial activity against both the multidrug resistant (K1) and sensitive (NF54) strains in the low nanomolar range. Some compounds displayed a significant reduction in potency in the hERG channel inhibition assay compared to previously reported frontrunner analogues. Several of these new analogues demonstrated promising in vivo efficacy in the Plasmodium berghei mouse model and will be further evaluated as potential clinical candidates. The SAR for in vitro antiplasmodial and hERG activity was delineated.
- González Cabrera, Diego,Douelle, Frederic,Younis, Yassir,Feng, Tzu-Shean,Le Manach, Claire,Nchinda, Aloysius T.,Street, Leslie J.,Scheurer, Christian,Kamber, Jolanda,White, Karen L.,Montagnat, Oliver D.,Ryan, Eileen,Katneni, Kasiram,Zabiulla, K. Mohammed,Joseph, Jayan T.,Bashyam, Sridevi,Waterson, David,Witty, Michael J.,Charman, Susan A.,Wittlin, Sergio,Chibale, Kelly
-
supporting information
p. 11022 - 11030
(2013/02/25)
-
- 1, 7 - DIAZACARBAZOLES AND THEIR USE IN THE TREATMENT OF CANCER
-
The invention relates to 1, 7-diazacarbazole compounds of Formula (I), (I-a) and (I-b) which are useful as kinase inhibitors, more specifically useful as checkpoint kinase 1 (chk 1) inhibitors, thus useful as cancer therapeutics. The invention also relates to compositions, more specifically pharmaceutical compositions comprising these compounds and methods of using the same to treat various forms of cancer and hyperproliferative disorders, as well as methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
- -
-
Page/Page column 78
(2011/07/07)
-
- PROCESS FOR THE MANUFACTURE OF PHARMACEUTICALLY ACTIVE COMPOUNDS
-
According to the present invention there are provided novel processes for the manufacture of the compound of formula 1 as well as novel synthesis routes for key intermediates used in those processes.
- -
-
Page/Page column 10-11
(2011/02/25)
-
- NEW ANTI-MALARIAL AGENTS
-
The present invention is related to a use of aminopyridine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to aminopyridine derivatives useful for the preparation of a pharm
- -
-
Page/Page column 35-36
(2011/08/04)
-
- Design of a series of bicyclic HIV-1 integrase inhibitors. Part 1: Selection of the scaffold
-
HIV integrase inhibitors based on a novel bicyclic pyrimidinone core is presented. Nine variations of the core scaffold are evaluated leading to optimization of the 6:6 core giving compound 48 with an EC50 of 3 nM against wild type HIV infected T-cells.
- Jones, Eric D.,Vandegraaff, Nick,Le, Giang,Choi, Neil,Issa, William,MacFarlane, Katherine,Thienthong, Neeranat,Winfield, Lisa J.,Coates, Jonathan A.V.,Lu, Long,Li, Xinming,Feng, Xiao,Yu, Changjiang,Rhodes, David I.,Deadman, John J.
-
scheme or table
p. 5913 - 5917
(2010/11/18)
-
- PYRAZOLE COMPOUNDS
-
The present invention is directed to compounds of Formula (I) and to pharmaceutically acceptable salts thereof, their synthesis, and their use as Raf inhibitors.
- -
-
Page/Page column 66-67
(2009/03/07)
-
- PYRIDINE BENZAMIDES AND PYRAZINE BENZAMIDES USED AS PKD INHIBITORS
-
The present invention pertains generally to the field of therapeutic compounds,. arid more specifically to certain pyridine benzamide and pyrazine benzamide compounds (I) (referred to herein as PDBA and PZBA compounds) which, inter alia, inhibit protein kinase D (PKD) (e.g., PKD1, PKD2, PKD3). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PKD, and in the treatment of diseases and conditions that are mediated by PKD1 that are ameliorated by the inhibition of PKD, etc., including proliferative conditions such as cancer, etc.
- -
-
Page/Page column 96-97
(2008/12/06)
-
- FUSED RING HETEROCYCLE KINASE MODULATORS
-
The present invention provides fused ring heterocycles as kinase modulators, pharmaceutical compositions containing these modulators, and methods of using these modulators to treat diseases mediated by kinase activity.
- -
-
Page/Page column 70
(2008/12/04)
-
- PYRROLO-PYRIDINE KINASE MODULATORS
-
The present invention provides novel pyrrolo-pyridine kinase modulators and methods of using the novel pyrrolo-pyridine kinase modulators to treat diseases mediated by kinase activity.
- -
-
Page/Page column 90
(2008/12/04)
-
- BETA-AMYLOID PET IMAGING AGENTS
-
Novel derivatives of imidazopyridinylbenzeneamines and novel derivatives of benzothiazolylbenzeneamines are disclosed that offer improved behavior when used as imaging agents for positron emission tomography of beta-amyloids. Also disclosed is a palladium-catalyzed reaction scheme under microwave conditions for aryl thioethers in general that provides a high ratio of substitution relative to reduction and can be used for the imidazopyridinylbenzeneamine derivatives as well as other compounds of related structure.
- -
-
Page/Page column 24
(2008/06/13)
-
- Pyrrolo-pyridine kinase modulators
-
The present invention provides novel pyrrolo-pyridine kinase modulators and methods of using the novel pyrrolo-pyridine kinase modulators to treat diseases mediated by kinase activity.
- -
-
Page/Page column 74
(2010/02/15)
-
- Method for synthesis of AZA-annelated pyrroles, thiophenes, and furans
-
Methods of synthesis of intermediates that are useful as bioisosteres of the indole, benzofuran and benzothiophene scaffold are disclosed.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- 1,2-DIHYDROPYRIDINE COMPOUNDS, PROCESS FOR PREPARATION OF THE SAME AND USE THEREOF
-
The present invention provides a novel compound having an excellent AMPA receptor inhibitory action and/or kainate inhibitory action. A compound represented by the following formula, a salt thereof or hydrates thereof. In the formula, Q indicates NH, O or S; and R1, R2, R3, R4 and R5 are the same as or different from each other and each indicates hydrogen atom, a halogen atom, a C1-6 alkyl group or a group represented by the formula -X-A (wherein X indicates a single bond, an optionally sbutituted C1-6 alkylene group etc.; and A indicates an optionally substituted C6-14 aromatic hydrocarbocyclic group or 5- to 14-membered aromatic heterocyclic group etc.).
- -
-
-
