- HETEROARYL SUBSTITUTED 3-(1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF
-
The present disclosure provides a compound of Formula (I): (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein Rx and X1 are as defined herein, and methods of making and using same.
- -
-
Page/Page column 327-328
(2022/02/15)
-
- METHODS OF MANUFACTURING A BIFUNCTIONAL COMPOUND, ULTRAPURE FORMS OF THE BIFUNCTIONAL COMPOUND, AND DOSAGE FORMS COMPRISING THE SAME
-
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.
- -
-
-
- INHIBITOR COMPOUNDS
-
The disclosure relates to heterocyclic compounds and methods for their preparation. The disclosure provides compounds that may have beneficial therapeutic activity in the treatment of a disease or condition mediated by excessive or otherwise undesirable Des1 and/or fibrotic activity.
- -
-
Page/Page column 63; 85; 90-91
(2021/01/29)
-
- Development of a Scalable Synthesis of the Small Molecule TGFβR1 Inhibitor BMS-986260
-
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
-
p. 1310 - 1320
(2020/07/24)
-
- VINYL COMPOUNDS AS FGFR AND VEGFR INHIBITORS
-
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.
- -
-
-
- 2-ARYLSULFONAMIDO-N-ARYLACETAMIDE DERIVATIZED STAT3 INHIBITORS
-
The present disclosure provides pharmaceutical compositions comprising 2-arylsulfonamido-N-arylacetamide derivatized Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of their use.
- -
-
Paragraph 00770; 00772; 00781; 00783
(2018/08/20)
-
- Piperazine derivatives and their use as therapeutic agents
-
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.
- -
-
-
- TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
-
The present invention is directed to substituted five membered heteroaryl benzamide compounds compounds of formula (I), which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.
- -
-
Page/Page column 49
(2015/12/08)
-
- CXCR7 ANTAGONISTS
-
Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.
- -
-
Paragraph 0333; 0334
(2014/06/23)
-
- NOVEL COMPOUNDS FOR MODULATION OF ROR-GAMMA ACTIVITY
-
The present invention relates to aryl sulfones and related compounds that are modulators of ROR-gamma receptors. The invention also provides pharmaceutical compositions comprising these modulators, and methods of modulating ROR-gamma receptors using them. Also provided are methods of using aryl sulfones and related compounds as modulators of ROR-gamma to treat ROR-gamma mediated diseases
- -
-
Paragraph 00320
(2014/03/22)
-
- 3 (3-Pyrimidin-2-ylbenzyl)-1,2,4-triazolo[4,3-b]pyridazine derivatives
-
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
- -
-
Page/Page column 19-21
(2011/10/31)
-
- Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitors
-
Potent and orally bioavailable SCD inhibitors built on an azetidinyl pyridazine scaffold were identified. In a one-month gDIO mouse model of obesity, we demonstrated that there was no therapeutic index even at low doses; efficacy in preventing weight gain
- Isabel, Elise,Powell, David A.,Black, W. Cameron,Chan, Chi-Chung,Crane, Sheldon,Gordon, Robert,Guay, Jocelyne,Guiral, Sebastien,Huang, Zheng,Robichaud, Jo?l,Skorey, Kathryn,Tawa, Paul,Xu, Lijing,Zhang, Lei,Oballa, Renata
-
scheme or table
p. 479 - 483
(2011/02/28)
-
- 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
-
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
-
experimental part
p. 3814 - 3830
(2010/07/05)
-
- ALPHA-KETO HETEROCYCLES AS FAAH INHIBITORS
-
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.
- -
-
Page/Page column 85-86
(2010/04/03)
-
- Optimization of the central heterocycle of α-ketoheterocycle inhibitors of fatty acid amide hydrolase
-
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.
-
supporting information; experimental part
p. 4392 - 4403
(2009/06/17)
-
- HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
-
Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and
- -
-
Page/Page column 36
(2008/06/13)
-
- HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
-
Heteroaromatic compounds of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and
- -
-
Page/Page column 43
(2008/06/13)
-
- AZETIDINE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
-
Azetidine derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease; atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; liver steatosis; and non-alcoholic steatohepatitis. (I)
- -
-
Page/Page column 36
(2008/06/13)
-
- HETEROCYCLIC DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
-
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.
- -
-
Page/Page column 43
(2010/10/20)
-
- SUBSTITUTED TRIAZOLE DERIVATIVES AS OXYTOCIN ANTAGONISTS
-
The present invention relates to a class of substituted 1,2,4-triazoles of formula (I) with activity as oxytocin antagonists, uses thereof, processes for the preparation thereof and compositions containing, said, inhibitors. These inhibitors have utility in a variety of therapeutic areas including sexual dysfunction, particularly premature ejaculation (P.E.).
- -
-
Page/Page column 84
(2010/02/11)
-
- NEW COMPOUNDS
-
The present invention relates to new compounds of formula I, (I) a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.
- -
-
-
