- METHODS OF MANUFACTURING A BIFUNCTIONAL COMPOUND, ULTRAPURE FORMS OF THE BIFUNCTIONAL COMPOUND, AND DOSAGE FORMS COMPRISING THE SAME
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The present disclosure relates to ultra-pure forms, polymorphs, amorphous forms, and formulations of N-[(1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl]-6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyridazine-3-carboxamide, referred to herein as Compound A: The present disclosure also relates methods of manufacturing and purifying the same, as well as intermediates useful in the synthesis of Compound A. The ultra-pure forms, polymorphs, amorphous forms, and formulations of Compound A can be used as therapeutic agents for the treatment of various diseases and conditions such as cancer.
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- PYRIDAZINONE COMPOUNDS FOR THE TREATMENT OF NEUROMUSCULAR DISEASES
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Substituted pyridazinone compounds, conjugates, and pharmaceutical compositions for use in the treatment of neuromuscular diseases, such as Duchenne Muscular Dystrophy (DMD), are disclosed herein. The disclosed compounds are useful, among other things, in the treating of DMD and modulating inflammatory inhibitors IL-1, IL-6 or TNF-α.
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Paragraph 0289
(2021/11/20)
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- Development of a Scalable Synthesis of the Small Molecule TGFβR1 Inhibitor BMS-986260
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A scalable route to the small molecule TGFβR1 inhibitor BMS-986260 (1) was developed. This alternative approach circumvented the purification of intermediates by column chromatography and provided access to multikilogram quantities of the key intermediate
- Vetrichelvan, Muthalagu,Rakshit, Souvik,Chandrasekaran, Sathishkumar,Chinnakalai, Karthikeyan,Darne, Chetan Padmakar,Doddalingappa, Dyamanna,Gopikumar, Indasi,Gupta, Anuradha,Gupta, Arun Kumar,Karmakar, Ananta,Lakshminarasimhan, Thirumalai,Leahy, David K.,Palani, Senthil,Radhakrishnan, Vignesh,Rampulla, Richard,Savarimuthu, Antony,Subramanian, Varadharajan,Velaparthi, Upender,Warrier, Jayakumar,Eastgate, Martin D.,Borzilleri, Robert M.,Mathur, Arvind,Vaidyanathan, Rajappa
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p. 1310 - 1320
(2020/07/24)
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- VINYL COMPOUNDS AS FGFR AND VEGFR INHIBITORS
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FGFR and VEGFR inhibitors are provided, and compounds represented by formula (1) or formula (II) as FGFR and VEGFR inhibitors, pharmaceutically acceptable salts or tautomers thereof are specifically disclosed.
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- Piperazine derivatives and their use as therapeutic agents
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Compounds for treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the compounds are of formula (I): where x y, W, V, R 2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 7a , R 8 , R 8a , R 9 and R 9a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
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Paragraph 0124
(2016/03/19)
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- TBK/IKK INHIBITOR COMPOUNDS AND USES THEREOF
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The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.
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- NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
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Compounds of Formula I: are HIV reverse transcriptase inhibitors, wherein R1, R2, RE, L, M and Z are defined herein. The compounds of Formula I and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines
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Page/Page column
(2014/04/18)
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- 5-PHENOXY-3H-PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS HIV REVERSE TRANSCRIPTASE INHIBITORS
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Compounds of Formula (I) are HIV reverse transcriptase inhibitors, wherein R1, R2, RE, L, M and Z are defined herein. The compounds of Formula (I) and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
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Page/Page column 94; 95
(2014/05/07)
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- 3 (3-Pyrimidin-2-ylbenzyl)-1,2,4-triazolo[4,3-b]pyridazine derivatives
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Compounds of the formula (I), in which R1, R2, R3, R3′, R4 have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for th
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Page/Page column 19; 21
(2011/10/31)
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- INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS
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Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.
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Page/Page column 30; 31; 32
(2011/05/08)
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- Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): Structure-activity relationships leading to the identification of 6-((5 S,9 R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7- triazaspiro[4.4]nonan-7-yl)nico
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Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or αLβ2, belongs to the β2 integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellu
- Watterson, Scott H.,Xiao, Zili,Dodd, Dharmpal S.,Tortolani, David R.,Vaccaro, Wayne,Potin, Dominique,Launay, Michele,Stetsko, Dawn K.,Skala, Stacey,Davis, Patric M.,Lee, Deborah,Yang, Xiaoxia,McIntyre, Kim W.,Balimane, Praveen,Patel, Karishma,Yang, Zheng,Marathe, Punit,Kadiyala, Pathanjali,Tebben, Andrew J.,Sheriff, Steven,Chang, Chiehying Y.,Ziemba, Theresa,Zhang, Huiping,Chen, Bang-Chi,Delmonte, Albert J.,Aranibar, Nelly,McKinnon, Murray,Barrish, Joel C.,Suchard, Suzanne J.,Murali Dhar
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experimental part
p. 3814 - 3830
(2010/07/05)
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- ALPHA-KETO HETEROCYCLES AS FAAH INHIBITORS
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The invention provides a series of -alpha ketoheterocyclic compounds, for example, compounds of formula (I). The compounds can inhibit fatty acid amide hydrolase and can be useful for treatment of malconditions modulated by fatty acid amide hydrolase. The invention further provides methods of making compounds of formula (I), useful intermediates for the preparation of compounds of formula (I), and methods of using compounds of formula (I) and compositions thereof.
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Page/Page column 85
(2010/04/03)
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- Optimization of the central heterocycle of α-ketoheterocycle inhibitors of fatty acid amide hydrolase
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The synthesis and evaluation of a refined series of α- ketoheterocycles based on the oxazole 2 (OL-135) incorporating systematic changes in the central heterocycle bearing a key set of added substituents are described. The nature of the central heterocycle, even within the systematic and minor perturbations explored herein, significantly influenced the inhibitor activity. 1,3,4-oxadiazoles and 1,2,4-oxadiazoles 9 > tetrazoles, the isomeric 1,2,4-oxadiazoles 10, 1,3,4-thiadiazoles > oxazoles including 2 > 1,2-diazines > thiazoles > 1,3,4-triazoles. Most evident in these trends is the observation that introduction of an additional heteroatom at position 4 (oxazole numbering, N > O > CH) substantially increases activity that may be attributed to a reduced destabilizing steric interaction at the FAAH active site. Added heterocycle substituents displaying well-defined trends may be utilized to enhance the inhibitor potency and, more significantly, to enhance the inhibitor selectivity. These trends, exemplified herein, emerge from both enhancements in the FAAH activity and simultaneous disruption of binding affinity for competitive off-target enzymes.
- Garfunkle, Joie,Ezzili, Cyrine,Rayl, Thomas J.,Hochstatter, Dustin G.,Hwang, Inkyu,Boger, Dale L.
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supporting information; experimental part
p. 4392 - 4403
(2009/06/17)
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- HETEROCYCLIC DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
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Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where x, y, G, J, K, L, M, V R2, R3, R4, R5, R5a, R6, R6a, R7, R7a, R8 and R8a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
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Page/Page column 43
(2010/10/20)
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- CONDENSED FURAN DERIVATIVES AS ADENOSINE ANTAGONISTS
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A novel compound of the following formula (I): wherein Z is a phenyl or pyridyl which condenses to a furan ring; X is CH or N; R1 is hydrogen or optionally substituted lower alkyl; R2 is hydrogen, halogen or lower alkoxy; and R3
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