- DIFLUOROCYCLOHEXYL DERIVATIVES AS IL-17 MODULATORS
-
A series of substituted 4,4-difluorocyclohexyl derivatives as defined herein, being potent modulators of human IL-17 activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including inflammatory and autoimmune disorders.
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Page/Page column 84-85
(2021/09/04)
-
- Organophotoredox-Catalyzed Decarboxylative C(sp3)-O Bond Formation
-
This manuscript reports a visible-light-mediated organosulfide catalysis that enables the decarboxylative coupling between simple aliphatic alcohol and tertiary or secondary alkyl carboxylic acid-derived redox active esters to produce a C(sp3)-O-C(sp3) fragment. Results of the coupling using other heteroatom nucleophiles such as water, amides, and thiols are also described.
- Shibutani, Shotaro,Kodo, Taiga,Takeda, Mitsutaka,Nagao, Kazunori,Tokunaga, Norihito,Sasaki, Yusuke,Ohmiya, Hirohisa
-
supporting information
p. 1211 - 1216
(2020/02/04)
-
- A General Method for Photocatalytic Decarboxylative Hydroxylation of Carboxylic Acids
-
A general and practical method for decarboxylative hydroxylation of carboxylic acids was developed through visible light-induced photocatalysis using molecular oxygen as the green oxidant. The addition of NaBH4 to in situ reduce the unstable peroxyl radical intermediate much broadened the substrate scope. Different sp3 carbon-bearing carboxylic acids were successfully employed as substrates, including phenylacetic acid-type substrates, as well as aliphatic carboxylic acids. This transformation worked smoothly on primary, secondary, and tertiary carboxylic acids.
- Khan, Shah Nawaz,Zaman, Muhammad Kashif,Li, Ruining,Sun, Zhankui
-
p. 5019 - 5026
(2020/05/01)
-
- PDE9 inhibitor and uses thereof
-
The invention belongs to the technical field of medicines, particularly relates to a PDE9 inhibitor compound shown as a formula (I) or pharmaceutically acceptable salt, isomer, a deuterated compound,metabolite and prodrug thereof, and further relates to pharmaceutical preparations, pharmaceutical compositions and application of the compounds. X1, X2, X3, X4, R1, R2, ring A, L and m are defined inthe specification. The compounds can be used for preparing medicines for treating or preventing related diseases mediated by PDE9.
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-
Paragraph 0287; 0288; 0289; 0290
(2020/08/12)
-
- Hindered dialkyl ether synthesis with electrogenerated carbocations
-
Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions1,2. Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcohols and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. The use of molecular probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined. The reaction manifold that we report here demonstrates the power of electrochemistry to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates.
- Xiang, Jinbao,Shang, Ming,Kawamata, Yu,Lundberg, Helena,Reisberg, Solomon H.,Chen, Miao,Mykhailiuk, Pavel,Beutner, Gregory,Collins, Michael R.,Davies, Alyn,Del Bel, Matthew,Gallego, Gary M.,Spangler, Jillian E.,Starr, Jeremy,Yang, Shouliang,Blackmond, Donna G.,Baran, Phil S.
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p. 398 - 402
(2019/11/05)
-
- PDE9 inhibitor and application thereof
-
The invention belongs to the technical field of medicine and particularly relates to a PDE9 inhibitor compound shown as formula (I) or its pharmaceutically acceptable salts and stereoisomers, as wellas pharmaceutical preparations and pharmaceutical compositions of these compounds, and their application. The compounds herein are applicable to the preparation of drugs to treat or prevent PDE9-mediated related diseases.
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Paragraph 0678-0681
(2019/04/17)
-
- FUSED RING HETEROARYL COMPOUNDS AND THEIR USE AS TRK INHIBITORS
-
The disclosure provides novel chemical compounds represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof. The compounds can be used as an inhibitor of Trk and are useful in the treatment of pain, cancer, inflammation, neurodegenerative disease and certain infectious diseases. In some compounds of Formula I, Q is —CH═CR3C(O)NR4R5, —C≡CC(O)NR4R5, or
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-
Paragraph 0602; 0603
(2016/07/05)
-
- DOPAMINE D2 RECEPTOR LIGANDS
-
The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.
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Page/Page column 151; 154
(2016/07/05)
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- PYRAZOLOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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-
Paragraph 26
(2015/09/23)
-
- PYRAZOLOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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Page/Page column 23; 24
(2015/09/22)
-
- Pyrazolopyrimidine Macrocycles as Inhibitors of Human Immunodeficiency Virus Replication
-
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compound
- -
-
Paragraph 0093
(2015/09/22)
-
- IMIDAZOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. I
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Page/Page column 24
(2015/09/23)
-
- TYK2 INHIBITORS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
- -
-
Paragraph 001155; 001156
(2015/09/28)
-
- PYRIDIN-3-YL ACETIC ACID MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compound
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-
Page/Page column 21
(2015/09/23)
-
- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compou
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-
Page/Page column 78
(2014/03/22)
-
- 2-(HETERO)ARYL-BENZIMIDAZOLE AND IMIDAZOPYRIDINE DERIVATIVES AS INHIBITORS OF ASPARAGIME EMETHYL TRANSFERASE
-
Substituted benzimidazole and 3H-imidazo[4,5-b]pyridines or formula I: where X and Y respectively are selected from: (i) N and N; and (ii) N and CR4; A2 is selected from:, a C5 heteroarylene group, containing 2 or 3 ring heteroatoms, where the bonds to L1 and the core are β to one another; L1 is selected from: (i)A1-O-CH2-A2; (ii)A1-CH2-O-A2; (iii)A1-C(=O)-NH-A2; (iv)A1-CH(OH)-A2; (v)A1-CH2-NH-C(=O)-A2; (vi) A1-S-CH2-A2; (vii)A1- CH2-S-A2; (viii)A1-CH2-A2; and (ix)A1-CH(CH3)-O-A2; A1 is phenyl, optionally substituted by F or CF3; their use as pharmaceuticals, and in particular, in treating cancer and hemoglobinopathies.
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-
Page/Page column 156
(2014/09/03)
-
- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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-
Page/Page column 32; 33
(2014/10/18)
-
- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. Formule (I)
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-
Page/Page column 25
(2014/10/18)
-
- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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-
Page/Page column 68; 69
(2014/10/15)
-
- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
-
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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Page/Page column 41; 42
(2014/10/15)
-
- BENZODIOXANE INHIBITORS OF LEUKOTRIENE PRODUCTION FOR COMBINATION THERAPY
-
The present invention relates to a combination comprising compounds of formula (I): wherein R1 to R3, A, X and n are as defined herein, and an additional active agent. The present invention also relates to pharmaceutical compositions comprising these combinations, and methods of using these combinations to treat various diseases and disorders.
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-
Paragraph 0321
(2013/09/26)
-
- Direct construction of quaternary carbons from tertiary alcohols via photoredox-catalyzed fragmentation of tert-alkyl N-phthalimidoyl oxalates
-
A convenient method for the direct construction of quaternary carbons from tertiary alcohols by visible-light photoredox coupling of tert-alkyl N-phthalimidoyl oxalate intermediates with electron-deficient alkenes is reported.
- Lackner, Gregory L.,Quasdorf, Kyle W.,Overman, Larry E.
-
supporting information
p. 15342 - 15345
(2013/11/06)
-
- KINASE INHIBITORS
-
Compounds of formula (I) or a pharmaceutically acceptable salt thereof: formula (I) wherein R2, W, A, Y and R1 are as defined in the specification, are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
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Page/Page column 278
(2013/06/27)
-
- KINASE INHIBITORS
-
Compounds of formula (I) and pharmaceutically acceptable salts thereof: wherein R2, W, A, Y and R1 are as defined in the specification, are p38 MAPK inhibitors, and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
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-
Paragraph 1050; 1051
(2013/06/27)
-
- BENZODIOXANES FOR INHIBITING LEUKOTRIENE PRODUCTION
-
The present invention relates to compounds of formula (I) wherein R1 to R3, A, X and n are as defined herein. The compounds of formula (I) are useful as inhibitors of leukotriene A4 hydrolase (LTA4H) and treating LTA4H related disorder. The present invention also relates to pharmaceutical compositions comprising the compounds of formula (I), methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.
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Page/Page column 91; 92
(2013/09/26)
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- 2-SUBSTITUTED-ETHYNYLTHIAZOLE DERIVATIVES AND USES OF SAME
-
The present invention provides 2-substituted-ethynylthiazole derivatives of formula (I): wherein R1, R2 and X are as defined herein, or a pharmaceutically acceptable salt thereof; and pharmaceutical compositions and methods of using same.
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Page/Page column 19
(2011/05/03)
-
- PHTHALAZINONE DERIVATIVES
-
A compound of the formula (I): wherein: A and B together represent an optionally substituted, fused aromatic ring; X and Y are selected from CH and CH, CF and CH, CH and CF and N and CH respectively; RC is selected from H, C1-4 alkyl
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-
Page/Page column 27-28
(2009/08/14)
-
- DIAZACARBAZOLES AND METHODS OF USE
-
The invention relates to 1,7-diazacarbazole compounds of Formula (I), (I-a) and (I-b) which are useful as kinase inhibitors, more specifically useful as checkpoint kinase 1 (chkl) inhibitors, thus useful as cancer therapeutics. The invention also relates to compositions, more specifically pharmaceutical compositions comprising these compounds and methods of using the same to treat various forms of cancer and hyperproliferative disorders, as well as methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 148-149
(2010/01/07)
-
- PYRAZOLYL-AMINO-SUBSTITUTED PYRIMIDINES AND THEIR USE FOR THE TREATMENT OF CANCER
-
The present invention relates to compounds of Formula (I) and to their pharmaceutical compositions, and to their methods of use. These compounds provide a treatment for myeloproliferative disorders and cancer.
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Page/Page column 96
(2008/12/08)
-
- INHIBITORS OF SERINE PALMITOYLTRANSFERASE
-
This invention provides compounds of the formula (I) useful in the inhibition or modulation of serine palmitoyl transferase and their use in methods of treatment or amelioration of type 2 diabetes, type 1 diabetes, insulin resistance, the effects of obesity, metabolic syndrome (sometimes referred to as Syndrome X), impaired glucose tolerance, Cushing's disease, cardiovascular disease, prothrombotic conditions, myocardial infarction, hypertension, congestive heart failure, cardiomyopathy, atherosclerosis, dyslipidemia, sepsis, liver damage, retinal degenerative disorders, cachexia, emphysema, hepatitis C infections, HIV infections and inflammatory disorders and useful in methods for raising HDL plasma levels in a mammal. The compounds of this invention can also be used to prevent damage or loss of pancreatic islet beta cells (such as in the case of pancreatic beta cell apoptosis, including those related to insulin-dependent diabetes mellitus).
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Page/Page column 105
(2008/12/07)
-
- 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.
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Page/Page column 49
(2010/11/26)
-
- HETEROCYCLIC DERIVATIVES AND THEIR USE AS MEDIATORS OF STEAROYL-COA DESATURASE
-
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): Formula (I) where x, y, G, J, L, M, V, W, 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 47
(2010/10/20)
-
- N-Acylsulfonamide apoptosis promoters
-
N-Benzoyl arylsulfonamides having the formula Are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.
- -
-
-
- N-acylsulfonamide apoptosis promoters
-
N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.
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-