- INHIBITING USP36
-
The present disclosure is directed to compounds of formulas (I) - (VI), which are useful as modulators of USP36. The compounds are further useful in the inhibition of USP36 and the treatment of diseases or disorders associated with the inhibition of USP36
- -
-
Paragraph 0152; 0157
(2020/11/13)
-
- A Dipolar Cycloaddition Reaction to Access 6-Methyl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridines Enables the Discovery Synthesis and Preclinical Profiling of a P2X7 Antagonist Clinical Candidate
-
A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure-activity relati
- Chrovian, Christa C.,Soyode-Johnson, Akinola,Peterson, Alexander A.,Gelin, Christine F.,Deng, Xiaohu,Dvorak, Curt A.,Carruthers, Nicholas I.,Lord, Brian,Fraser, Ian,Aluisio, Leah,Coe, Kevin J.,Scott, Brian,Koudriakova, Tatiana,Schoetens, Freddy,Sepassi, Kia,Gallacher, David J.,Bhattacharya, Anindya,Letavic, Michael A.
-
supporting information
p. 207 - 223
(2018/02/10)
-
- Identification of (R)-(2-Chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyridin-2-yl)-4-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone (JNJ 54166060), a Small Molecule Antagonist of the P2X7 receptor
-
The synthesis and SAR of a series of 4,5,6,7-tetrahydro-imidazo[4,5-c]pyridine P2X7 antagonists are described. Addressing P2X7 affinity and liver microsomal stability issues encountered with this template afforded methyl substituted 4,5,6,7-tetrahydro-imidazo[4,5-c]pyridines ultimately leading to the identification of 1 (JNJ 54166060). 1 is a potent P2X7 antagonist with an ED50 = 2.3 mg/kg in rats, high oral bioavailability and low-moderate clearance in preclinical species, acceptable safety margins in rats, and a predicted human dose of 120 mg of QD. Additionally, 1 possesses a unique CYP profile and was found to be a regioselective inhibitor of midazolam CYP3A metabolism.
- Swanson, Devin M.,Savall, Brad M.,Coe, Kevin J.,Schoetens, Freddy,Koudriakova, Tatiana,Skaptason, Judith,Wall, Jessica,Rech, Jason,Deng, Xiahou,De Angelis, Meri,Everson, Anita,Lord, Brian,Wang, Qi,Ao, Hong,Scott, Brian,Sepassi, Kia,Lovenberg, Timothy W.,Carruthers, Nicholas I.,Bhattacharya, Anindya,Letavic, Michael A.
-
p. 8535 - 8548
(2016/10/03)
-
- Concise preparation of a stable cyclic sulfamidate intermediate in the synthesis of a enantiopure chiral active diamine derivative
-
A classical resolution was studied and developed from 2-benzoyl-pyridine in order to prepare SSR504734, a novel antipsychotic derivative. The key step of this route is the substitution of a sulfamidate derivative by a benzamide anion with complete inversi
- Rousseau, Jean-Francois,Chekroun, Isaac,Ferey, Vincent,Labrosse, Jean Robert
-
p. 506 - 513
(2015/04/27)
-
- P2X7 MODULATORS
-
The present invention is directed to a compound of Formula (I) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.
- -
-
Paragraph 0404; 0405; 0406
(2014/09/30)
-
- P2X7 MODULATORS
-
The present invention is directed to a compound of Formula (I): The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invent
- -
-
Paragraph 0209
(2014/09/29)
-
- P2X7 MODULATORS
-
The present invention is directed to compounds of Formulas (I, IIa and IIb): The invention also relates to pharmaceutical compositions comprising compounds of Formulas (I, IIa and IIb). Methods of making and using the compounds of Formulas (I, IIa and IIb) are also within the scope of the invention.
- -
-
Paragraph 0284
(2014/09/29)
-
- PYRROLIDINE SUBSTITUTED FLAVONES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
-
The present invention relates to the use of a compound of formula 1, a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, for the treatment of an inflammatory disorder. The invention further relates to a pharmaceutical composition comprising a compound of formula 1 and at least one pharmaceutically acceptable carrier, for use in the treatment of an inflammatory disorder. The invention also relates to a method for the treatment of an inflammatory disorder by administering a therapeutically effective amount of the compound of formula 1 to a subject in need thereof.
- -
-
Page/Page column 33
(2011/09/30)
-
- 2-AZA-BICYCLO[2.2.2]OCTANE COMPOUNDS AND USES THEREOF
-
This invention relates to 2-aza-bicyclo [2.2.2] octane compounds (and salts thereof), the process for making such a compound and pharmaceutical compositions comprising such a compound. The invention also relates to the use of the compounds for modulating
- -
-
Page/Page column 82
(2010/08/09)
-
- Novel Compounds 894
-
The invention relates to 2-aza-bicyclo[2.2.2]octane compounds and uses thereof. Particularly the invention relates to such compounds and their uses as pharmaceuticals in treating pyshoses such as schizophrenia and other diseases, disorders, or conditions.
- -
-
Page/Page column 30
(2009/02/11)
-
- P2X7 receptor antagonists and methods of use
-
The invention is directed to compounds that are P2X7 antagonist and have the formula (I) or (II) or a pharmaceutically acceptable salt, prodrug, salt of a prodrug or a combination thereof, wherein R1, R2, and R3 /sub
- -
-
Page/Page column 24
(2010/11/27)
-
- COMPOUNDS WHICH INHIBIT THE GLYCINE TRANSPORTER AND USES THEREOF
-
Compounds of formula (I) and salts and solvates are provided wherein R2 is selected from phenyl substituted with n R1 groups, and pyridyl substituted with n R1 groups; n = 0, 1 or 2; each R1 is independently selected from the group consisting of halo, C1-4alkyl, C1-4alkoxy, haloC1-4alkyl, haloC1-4alkoxy and cyano; R3 is selected from hydrogen and C1-2 alkyl; R4 is selected from the group consisting of ethyl, n- propyl, i-propyl, n-butyl, i-butyl and t-butyl; or R3 and R4 together with the nitrogen atom to which they are attached form a saturated 5- or 6-membered heterocyclic ring optionally substituted with one or more groups X; each X is independently selected from the group consisting of C1-4alkyl, and haloC1-4alkyl; R12 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, methyl and methylthio; R13 is selected from hydrogen, chloro and trifluoromethyl; R14 is selected from hydrogen, trifluoromethyl and chloro; R15 is selected from hydrogen, chloro and trifluoromethyl; R16 is selected from hydrogen, methyl, fluoro and chloro; R12, R13, R14, R15 and R16 not all simultaneously being hydrogen. Processes for the preparation and uses of the compounds as medicaments for treating disorders such as psychoses, dementia or attention deficit disorder are also disclosed.
- -
-
Page/Page column 35-36
(2008/06/13)
-
- THE USE OF SELECTIVE P2X7 RECEPTOR ANTAGONISTS
-
The present invention relates to the use of selective P2X7 receptor antagonists of formula (I), or a pharmaceutically acceptable salt or prodrug thereof wherein D, R1 and R2 are as defined in claim 1, for the treatment of neuropathic pain, chronic inflammatory pain, inflammation, neurodegeneration and for promoting neuroregeneration.
- -
-
Page/Page column 69
(2008/06/13)
-
- Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists
-
1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X? receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution
- Nelson, Derek W.,Gregg, Robert J.,Kort, Michael E.,Perez-Medrano, Arturo,Voight, Eric A.,Wang, Ying,Grayson, George,Namovic, Marian T.,Donnelly-Roberts, Diana L.,Niforatos, Wende,Honore, Prisca,Jarvis, Michael F.,Faltynek, Connie R.,Carroll, William A.
-
p. 3659 - 3666
(2007/10/03)
-