- Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5- b]pyridazines for the Treatment of Human African Trypanosomiasis
-
From a high-throughput screen of 42 44 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against h
- Tear, Westley F.,Bag, Seema,Diaz-Gonzalez, Rosario,Ceballos-Pérez, Gloria,Rojas-Barros, Domingo I.,Cordon-Obras, Carlos,Pérez-Moreno, Guiomar,García-Hernández, Raquel,Martinez-Martinez, Maria Santos,Ruiz-Perez, Luis Miguel,Gamarro, Francisco,Gonzalez Pacanowska, Dolores,Caffrey, Conor R.,Ferrins, Lori,Manzano, Pilar,Navarro, Miguel,Pollastri, Michael P.
-
p. 756 - 783
(2020/02/04)
-
- IMIDAZO [1,2-B] PYRIDAZINE AND IMIDAZO [4,5-B] PYRIDINE DERIVATIVES AS JAK INHIBITORS
-
New imidazo[1,2-b]pyridazine and imidazo[4,5-b]pyridine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
- -
-
Page/Page column 50-51
(2012/06/15)
-
- Imidazo[1,2-b]pyridazine derivatives as JAK inhibitors
-
New imidazo[1,2-b]pyridazine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
- -
-
Page/Page column 20
(2012/06/18)
-
- Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines
-
Ring-closing olefin metathesis (RCM) has been applied to the efficient synthesis of densely and diversely substituted pyridine and pyridazine frameworks. Routes to suitable metathesis precursors have been investigated and the scope of the metathesis step has been probed. The metathesis products function as precursors to the target heteroaromatic structures via elimination of a suitable leaving group, which also facilitates earlier steps by serving as a protecting group at nitrogen. Further functionalisation of the metathesis products is possible both prior to and after aromatisation. The net result is a powerful strategy for the de novo synthesis of highly substituted heteroaromatic scaffolds.
- Donohoe, Timothy J.,Bower, John F.,Basutto, José A.,Fishlock, Lisa P.,Procopiou, Panayiotis A.,Callens, Cedric K.A.
-
experimental part
p. 8969 - 8980
(2009/12/26)
-
- Compounds and Uses Thereof - 848
-
This invention relates to novel compounds having the structural formula I below: and their pharmaceutically acceptable salts, tautomers or in vivo-hydrolysable precursors, compositions and methods of use thereof, wherein R1, R2, Rsu
- -
-
Page/Page column 74
(2009/01/24)
-
- PYRAZOLE DERIVATIVES
-
A compound represented by formula (I): (wherein Ar1 represents a phenyl group which may have 1 to 3 substituents, or a non-substituted 5- or 6-membered aromatic heterocyclic group; Ar2 represents (i) a non-substituted phenyl group, (ii) a phenyl group which has been substituted by a lower alkyl group having 1 to 3 groups or atoms selected from among a carbamoyl group, an amino group, a hydroxyl group, a lower alkoxy group, and a halogen atom, or (iii) a 5- or 6-membered nitrogen-containing aromatic heterocyclic group which has been substituted by 1 to 3 groups or atoms selected from among a lower alkyl group, a lower alkynyl group, a lower alkanoyl group, a carbamoyl group, a cyano group, an amino group, a hydroxyl group, a lower alkoxy group, and a halogen atom; and X represents a group represented by formula (II): (wherein the ring structure represents a 4- to 7-membered heterocyclic group which may have, in addition to the nitrogen atom shown in formula (II), one heteroatom selected from among nitrogen, oxygen, and sulfur, and which may be substituted by 1 to 4 groups or atoms selected from among a lower alkyl group, a carbamoyl group, an amino group, a hydroxyl group, a lower alkoxy group, an oxo group, a lower alkanoyl group, a lower alkylsulfonyl group, and a halogen atom)), a salt thereof, a solvate of the compound or the salt, and a drug.
- -
-
Page/Page column 51-52
(2010/11/26)
-
- Anti-tumor compounds
-
Compounds of the following formula: wherein A, D, Q, T, U, V, W, X, Y, Z, R1, and ---- are as defined herein. This invention also relates to a method of inhibiting tubulin polymerization, or treating cancer or an angiogenesis-related disorder w
- -
-
Page/Page column 13
(2008/06/13)
-
- N-phenyl-4-pyrazolo[1,5-6]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy
-
Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b] pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.
- Tavares, Francis X.,Boucheron, Joyce A.,Dickerson, Scott H.,Griffin, Robert J.,Preugschat, Frank,Thomso, Stephen A.,Wang, Tony Y.,Zhouf, Hui-Qiang
-
p. 4716 - 4730
(2007/10/03)
-