- Structure-Activity Relationship of para-Carborane Selective Estrogen Receptor β Agonists
-
Selective agonism of the estrogen receptor (ER) subtypes, ERα and ERβ, has historically been difficult to achieve due to the high degree of ligand-binding domain structural similarity. Multiple efforts have focused on the use of classical organic scaffold
- Sedlák, David,Wilson, Tyler A.,Tjarks, Werner,Radomska, Hanna S.,Wang, Hongyan,Kolla, Jayaprakash Narayana,Le?nikowski, Zbigniew J.,?pi?áková, Alena,Ali, Tehane,Ishita, Keisuke,Rakotondraibe, Liva Harinantenaina,Vibhute, Sandip,Wang, Dasheng,Anzenbacher, Pavel,Bennett, Chad,Bartunek, Petr,Coss, Christopher C.
-
p. 9330 - 9353
(2021/07/20)
-
- SUBSTITUTED AMIDE COMPOUNDS USEFUL AS FARNESOID X RECEPTOR MODULATORS
-
Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein Q is: (i) halo, cyano, hydroxyl, NRxRx, C(O)OH, C(O)NH2, C1-6 alkyl substituted with zero to 6 R1a, or P(O)R1cR1c; or (ii) L R1; and A, X1, X2, X3, X4, Z1, Z2, R1, R1a, R1c, R2, R3a, R3b, Rx, L, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
- -
-
Page/Page column 160; 161
(2020/08/28)
-
- SUBSTITUTED BICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
-
Disclosed are compounds of Formula (I) or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
- -
-
Page/Page column 166; 168
(2020/08/28)
-
- CARBORANE COMPOUNDS, CARBORANE ANALOGS, AND METHODS OF USE THEREOF
-
Disclosed are method of treating fibrotic conditions using carboranes and carborane analogs. Also disclosed herein are compounds comprising dicarba-closo-dodecaborane or a dicarba-closo-dodecaborane analog. The compounds can be, for example, estrogen rece
- -
-
Page/Page column 123-124
(2020/07/04)
-
- SUBSTITUTED AMIDE COMPOUNDS USEFUL AS FARNESOID X RECEPTOR MODULATORS
-
Disclosed are compounds of Formula (I) or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein Q is a 5-membered heterocyclyl or 5-membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O, and S, substituted with zero to 4 R1; and A, X1, X2, X3, X4, Z1, Z2, R1, R2, R3a, R3b, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
- -
-
Page/Page column 80-81
(2020/08/28)
-
- DIPHENYL DERIVATIVES AND USES THEREOF
-
The present disclosure provides a compound of formula (I): or a pharmaceutically acceptable salt thereof, and its therapeutic uses for activating a growth factor pathway, promoting wound healing, promoting tissue repair, and treating hearing loss, skeletal muscle loss, organ degeneration, tissue damage, neurodegeneration, and muscular atrophy. The disclosure further provides pharmaceutical compositions and combinations. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
- -
-
Paragraph 1309
(2019/03/30)
-
- Generation and Cross-Coupling of Organozinc Reagents in Flow
-
A versatile flow synthesis method for in situ formation of organozinc reagents and subsequent cross-coupling with aryl halides and activated carboxylic acids is reported. Formation of organozinc reagents is achieved by pumping organic halides, in the presence of ZnCl2 and LiCl, through an activated Mg-packed column under flow conditions. This method provides efficient in situ formation of aryl, primary, secondary, and tertiary alkyl organozinc reagents, which are subsequently telescoped downstream to a Negishi or decarboxylative Negishi cross-coupling reaction. The described method offers access to a variety of C-C bond formations with organozinc reagents that are otherwise commercially unavailable or difficult to prepare under traditional batch reaction conditions.
- Herath, Ananda,Molteni, Valentina,Pan, Shifeng,Loren, Jon
-
supporting information
p. 7429 - 7432
(2019/01/03)
-
- Substituted pyrazolo-piperazines as casein kinase 1 δ/ε inhibitors
-
The invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.
- -
-
Page/Page column 530
(2016/03/19)
-
- Redox-Active Esters in Fe-Catalyzed C-C Coupling
-
Cross-couplings of alkyl halides and organometallic species based on single electron transfer using Ni and Fe catalyst systems have been studied extensively, and separately, for decades. Here we demonstrate the first couplings of redox-active esters (both isolated and derived in situ from carboxylic acids) with organozinc and organomagnesium species using an Fe-based catalyst system originally developed for alkyl halides. This work is placed in context by showing a direct comparison with a Ni catalyst for >40 examples spanning a range of primary, secondary, and tertiary substrates. This new C-C coupling is scalable and sustainable, and it exhibits a number of clear advantages in several cases over its Ni-based counterpart.
- Toriyama, Fumihiko,Cornella, Josep,Wimmer, Laurin,Chen, Tie-Gen,Dixon, Darryl D.,Creech, Gardner,Baran, Phil S.
-
p. 11132 - 11135
(2016/10/12)
-
- COMBINATIONS OF HEPATITIS C VIRUS INHIBITORS
-
The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.
- -
-
Page/Page column 468; 469
(2015/02/02)
-
- Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors
-
This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration.
- Zhong, Min,Peng, Eric,Huang, Ningwu,Huang, Qi,Huq, Anja,Lau, Meiyen,Colonno, Richard,Li, Leping
-
p. 5731 - 5737
(2015/01/08)
-
- LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
-
Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.
- -
-
Paragraph 1093
(2014/07/23)
-
- Hepatitis C Virus Inhibitors
-
This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
- -
-
Page/Page column 84
(2010/10/19)
-
- Discovery of a potent, selective, and orally efficacious pyrimidinooxazinyl bicyclooctaneacetic acid diacylglycerol acyltransferase-1 inhibitor
-
Inhibition of DGAT-1 is increasingly seen as an attractive mechanism with the potential for treatment of obesity and other elements of the metabolic syndrome. We report here a bicyclooctaneacetic acid derivative in the pyrimidinooxazine structural class o
- Birch, Alan M.,Birtles, Susan,Buckett, Linda K.,Kemmitt, Paul D.,Smith, Graham J.,Smith, Tim J. D.,Turnbull, Andrew V.,Wang, Steven J. Y.
-
experimental part
p. 1558 - 1568
(2010/01/07)
-