- COMPOUNDS FOR USING IN IMAGING AND PARTICULARLY FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISEASES
-
The invention relates to compounds of formula (II) for using in imaging and particularly for the diagnosis of neurodegenerative diseases
- -
-
-
- Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells
-
A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N- hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT116 human cancer cell lines. Pharmacological studies indicated that 12 functions as a potent HDAC inhibitor with an IC50 value of 0.1 μM. It is highly selective for histone deacetylase 6 (HDAC6) and is 60-fold more active than against HDAC1 and 223-fold more active than against HDAC2. It has a good pharmacokinetic profile with oral bioavailability of 33%. In in vivo efficacy evaluations in colorectal HCT116 xenografts, compound 12 suppresses tumor growth more effectively than SAHA (1, N-hydroxy-N′- phenyloctanediamide) and is therefore seen as a suitable candidate for further investigation.
- Lee, Hsueh-Yun,Tsai, An-Chi,Chen, Mei-Chuan,Shen, Po-Jung,Cheng, Yun-Ching,Kuo, Ching-Chuan,Pan, Shiow-Lin,Liu, Yi-Min,Liu, Jin-Fen,Yeh, Teng-Kuang,Wang, Jing-Chi,Chang, Chi-Yen,Chang, Jang-Yang,Liou, Jing-Ping
-
p. 4009 - 4022
(2014/06/09)
-
- Novel 3-azaindolyl-4-arylmaleimides exhibiting potent antiangiogenic efficacy, protein kinase inhibition, and antiproliferative activity
-
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
- Ganser, Christopher,Lauermann, Eva,Maderer, Annett,Stauder, Torsten,Kramb, Jan-Peter,Plutizki, Stanislav,Kindler, Thomas,Moehler, Markus,Dannhardt, Gerd
-
p. 9531 - 9540
(2013/01/16)
-
- Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: Design, synthesis, structure-activity relationships, physicochemical properties and biological activity
-
The discovery, synthesis and structure-activity relationship (SAR) of a novel series of cannabinoid 1 (CB1) and cannabinoid 2 (CB 2) receptor ligands are reported. Based on the aminoalkylindole class of cannabinoid receptor agonists, a biphenyl moiety was introduced as novel lipophilic indole 3-acyl substituent in 11-16. Furthermore, the 3-carbonyl tether was replaced with a carboxamide linker in 17-20 and the azaindole (pyrrolopyridine) nucleus was designed as indole bioisostere with improved physicochemical properties in 21-25. Through these SAR efforts, several high affinity CB1/CB2 dual cannabinoid receptor ligands were identified. Indole-3-carboxamide 17 displayed single-digit nanomolar affinity and ～80 fold selectivity for CB1 over the CB2 receptor. The azaindoles displayed substantially improved physicochemical properties (lipophilicity; aqueous solubility). Azaindole 21 elicited potent cannabinoid activity. Cannabinoid receptor agonists 17 and 21 potently modulated excitatory synaptic transmission in an acute rat brain slice model of cannabinoid receptor-modulated neurotransmission.
- Blaazer, Antoni R.,Lange, Jos H.M.,Van Der Neut, Martina A.W.,Mulder, Arie,Den Boon, Femke S.,Werkman, Taco R.,Kruse, Chris G.,Wadman, Wytse J.
-
p. 5086 - 5098
(2011/11/29)
-
- KINASE INHIBITORS AND THEIR USE AS PHARMACEUTICAL AGENTS
-
Described herein are compounds that are inhibitors of one or more protein kinases. Also described are pharmaceutical compositions and medicaments that include the compounds described herein. Also described herein are methods of using such protein kinase inhibitors, alone and in combination with other compounds, for conditions or diseases mediated or dependent upon protein kinases
- -
-
-
- NOVEL 6-AZAINDOLE AMINOPYRIMIDINE DERIVATIVES HAVING NIK INHIBITORY ACTIVITY
-
The present invention relates to a compound of formula I: wherein: R1 is C1-6 alkyl, C3-8 cycloalkyl, aryl, heterocyclyl, or -COR1x, where the C1-6 alkyl, C3-8 cycloalkyl, aryl, and heterocyclyl may be substituted; and R1x is C3-8 cycloalkyl, aryl, or heterocyclyl, any of which may be substituted; R2, R3, R4, R5, R6, and R7 are each independently hydrogen, halogen, C1-6 alkyl, or aryl, where the C1-6 alkyl or aryl may be substituted; R8 is hydrogen, C1-6 alkyl, aryl, or heterocyclyl, any of which may be substituted; or a pharmaceutically acceptable salt or ester thereof.
- -
-
Page/Page column 46
(2010/04/28)
-
- KINASE INHIBITORS AND THEIR USE AS PHARMACEUTICAL AGENTS
-
Described herein are compounds that are inhibitors of one or more protein kinases. Also described are pharmaceutical compositions and medicaments that include the compounds described herein. Also described herein are methods of using such protein kinase inhibitors, alone and in combination with other compounds, for conditions or diseases mediated or dependent upon protein kinases.
- -
-
Page/Page column 50
(2010/06/11)
-
- Site-selective azaindole arylation at the azine and azole rings via N-oxide activation
-
Subjection of N-methyl 6-and 7-azaindole N-oxides to a Pd(OAc) 2/DavePhos catalyst system enables regioselective direct arylation of the azine ring. Following deoxygenation, 7-azaindole substrates undergo an additional regioselective azole direct arylation event in good yield.
- Huestis, Malcolm P.,Fagnou, Keith
-
supporting information; scheme or table
p. 1357 - 1360
(2009/09/05)
-
- 3-Amino-1-arylpropyl azaindoles and uses thereof
-
The present invention provides compounds of the formula: or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein p, Ar, R1, R2, R3, Ra, Rb, Rc, Rd and Re are defined herein. Also provided are pharmaceutical compositions, methods of using, and methods of preparing the compounds.
- -
-
Page/Page column 43
(2008/06/13)
-
- Azaindolylalkylamine derivatives as 5-hydroxytryptamine-6 ligands
-
The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.
- -
-
-
- A general method for the preparation of 4-and 6-azaindoles
-
Nitropyridines reacted with an excess of vinyl Grignard reagent to produce 4- or 6-azaindoles. Improved yields were obtained when a halogen atom was present at the position α to the nitrogen atom in the pyridine ring.
- Zhang, Zhongxing,Yang, Zhong,Meanwell, Nicholas A.,Kadow, John F.,Wang, Tao
-
p. 2345 - 2347
(2007/10/03)
-
- Chemical synthesis of azaindoles
-
The present invention relates to a process for the preparation of azaindole derivatives of the formula STR1 wherein Q is hydrogen, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy, aryl or arylC1-4 alkyl; one of X, Y and Z is --N= and the others are --CH=; R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl or C1-6 alkyl substituted by a group selected from aryl or --NR2 R3 where R2 and R3 each independently represent C1-4 alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, form a 4-7 membered saturated heterocyclic ring, optionally containing in the ring an oxygen or sulphur atom or a group NR4 where R4 is C1-4 alkyl, aryl or arylC1-4 alkyl; and R5 is a hydrogen atom or a group selected from C1-6 alkyl or aryl.
- -
-
-
- A convenient method for the preparation of 5-, 6- and 7-azaindoles and their derivatives
-
The directed ortho lithiation of 2-tert-butoxycarbonylamino-3-methylpyridine (6a) has provided a convenient method for the preparation of 1H-pyrrolo[2,3-b]pyridine (4a, 7-azaindole). This procedure has been used to prepare a range of 3-substituted 2-tert-butoxycarbonylaminopyridines 6, 2- and 3-substituted and 2,3-disubstituted 1H-pyrrolo[2,3-b]pyridines 4 and shown to be of value in the preparation of 1H-pyrrolo[3,2-c]pyridine (15, 5-azaindole) and 1H-pyrrolo[2,3-c]pyridine (18, 6-azaindole) and derivatives.
- Hands, David,Bishop, Brian,Cameron, Mark,Edwards, John S.,Cottrell, Ian F.,Wright, Stanley H. B.
-
p. 877 - 882
(2007/10/03)
-
- 6-AZAINDOLE THROMBOXANE SYNTHASE INHIBITORS
-
Selected acid functional 6-azaindole type derivatives effective as thromboxane synthase inhibitors having the formula (II):where n is an integer from zero to 3, m is an integer from zero to 2, R1 and R2 are monovalent radicals, -(La)- is a linking group of 4 to 8 chain atoms, and A is an acidic group
- -
-
-
- CONDENSED HETEROAROMATIC RING SYSTEMS. XXII. SIMPLE AND GENERAL SYNTHESIS OF 1H-PYRROLOPYRIDINES
-
Four kinds of 1H-pyrrolopyridines having no substituent were simply and easily synthesized by the palladium-catalyzed reaction of easily available nitropyridine derivatives with (Z)-1-ethoxy-2-tributylstannylethene as a key reaction.
- Sakamoto, Takao,Satoh, Chisato,Kondo, Yoshinori,Yamanaka, Hiroshi
-
p. 2379 - 2384
(2007/10/02)
-
