- Lead derivatization of ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate and 5-bromo-2-(thiophene-2-carboxamido) benzoic acid as FabG inhibitors targeting ESKAPE pathogens
-
Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B). The enzyme inhibition studies revealed that compound 15 (effective against EcFabG, AbFabG, StFabG, MtFabG1) and 19 (inhibiting EcFabG and StFabG) had potency of broad-spectrum inhibition on FabG panel.
- Varakala, Saiprasad Dasugari,Reshma, Rudraraju Srilakshmi,Schnell, Robert,Dharmarajan, Sriram
-
-
- Facile Synthesis of Alkylidene Phthalides by Rhodium-Catalyzed Domino C?H Acylation/Annulation of Benzamides with Aliphatic Carboxylic Acids
-
The Rh-catalyzed ortho-C(sp2)?H functionalization of 8-aminoquinoline-derived benzamides with aliphatic acyl fluorides generated in situ from the corresponding acids has been developed. This reaction initiated with 8-aminoquinoline-directed ortho-C(sp2)?H acylation, which was accompanied by subsequent intramolecular nucleophilic acyl substitution of amide group to produce alkylidene phthalides This approach exhibits high stereo-selectivity for Z-isomer products, and tolerates a variety of functional groups as well as aliphatic carboxylic acids with diverse structural scaffolds.
- Liu, Sien,He, Bangyue,Li, Hongyi,Zhang, Xiaofeng,Shang, Yaping,Su, Weiping
-
supporting information
p. 15628 - 15633
(2021/10/05)
-
- Improved synthesis of sterically encumbered heteroaromatic biaryls from aromatic β-keto esters
-
A protocol for the synthesis of hindered 4-aryl 2-aminopyrimidines from β–keto esters is described. The process employs trifluoroethanol as an essential additive to promote the guanidine condensation reaction, enabling the synthesis of 25 aryl- and heteroaryl substituted aminopyrimidines in good yields and high purities with no column chromatography. The conditions described herein are readily scalable and have been employed in the large-scale synthesis of the clinical A2a/A2bR antagonist AB928.
- Rosen, Brandon R.,Ul Sharif, Ehesan,Miles, Dillon H.,Chan, Nicholas S.,Leleti, Manmohan R.,Powers, Jay P.
-
supporting information
(2020/03/25)
-
- Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 2. Ketone Linked Analogs
-
The optimization of a series of benzimidazole-benzoxaborole hybrid molecules linked via a ketone that exhibit good activity against Onchocerca volvulus, a filarial nematode responsible for the disease onchocerciasis, also known as river blindness, is desc
- Carter, David S.,Jacobs, Robert T.,Freund, Yvonne R.,Berry, Pamela W.,Akama, Tsutomu,Easom, Eric E.,Lunde, Christopher S.,Rock, Fernando,Stefanakis, Rianna,Mckerrow, James,Fischer, Chelsea,Bulman, Christina A.,Lim, Kee Chong,Suzuki, Brian M.,Tricoche, Nancy,Sakanari, Judy A.,Lustigman, Sara,Plattner, Jacob J.
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p. 180 - 185
(2020/02/13)
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- Development of a Scalable and Practical Synthesis of AB928, a Dual A2a/A2bReceptor Antagonist
-
AB928 is a potent and selective dual antagonist of the A2a and A2b receptors, which is currently in clinical trials. Here, we report the development of two scalable and practical syntheses of AB928. The first-generation synthesis was used to successfully
- Debien, Laurent P. P.,Jeffrey, Jenna L.,Leleti, Manmohan R.,Miles, Dillon H.,Powers, Jay P.,Rosen, Brandon R.,Sharif, Ehesan U.
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p. 1254 - 1261
(2020/08/14)
-
- PROCESSES FOR PREPARING AMINOPYRIMIDINE COMPOUNDS
-
Provided herein are improved processes for preparing aminopyrimidine compounds of Formula (I). The disclosed processes advantageously proceed through a β-diketoester intermediate of Formula (A) and avoid the direct linking of a pyrimidine and phenyl moiet
- -
-
Paragraph 0079
(2020/12/29)
-
- N-Heterocyclic Carbene Catalyzed Photoenolization/Diels–Alder Reaction of Acid Fluorides
-
The combination of light activation and N-heterocyclic carbene (NHC) organocatalysis has enabled the use of acid fluorides as substrates in a UVA-light-mediated photochemical transformation previously observed only with aromatic aldehydes and ketones. Stoichiometric studies and TD-DFT calculations support a mechanism involving the photoactivation of an ortho-toluoyl azolium intermediate, which exhibits “ketone-like” photochemical reactivity under UVA irradiation. Using this photo-NHC catalysis approach, a novel photoenolization/Diels–Alder (PEDA) process was developed that leads to diverse isochroman-1-one derivatives.
- Agrawal, Arush,G?tze, Jan P.,Golz, Paul,Hopkinson, Matthew N.,Mavroskoufis, Andreas,Rajes, Keerthana,Ru?, Vincent
-
supporting information
p. 3190 - 3194
(2020/01/24)
-
- Rhodium-Catalyzed Alkylation of C?H Bonds in Aromatic Amides with Non-activated 1-Alkenes: The Possible Generation of Carbene Intermediates from Alkenes
-
The alkylation of C?H bonds (hydroarylation) in aromatic amides with non-activated 1-alkenes using a rhodium catalyst and assisted by an 8-aminoquinoline directing group is reported. The addition of a carboxylic acid is crucial for the success of this reaction. The results of deuterium-labeling experiments indicate that one of deuterium atoms in the alkene is missing, suggesting that the reaction does not proceed through the commonly accepted mechanism for C?H alkylation reactions. Instead the reaction is proposed to proceed through a carbene mechanism. The carbene mechanism is also supported by preliminary DFT calculations.
- Yamaguchi, Takuma,Natsui, Satoko,Shibata, Kaname,Yamazaki, Ken,Rej, Supriya,Ano, Yusuke,Chatani, Naoto
-
supporting information
p. 6915 - 6919
(2019/05/10)
-
- Cobalt-Catalyzed C-H Iodination of Aromatic Amides with Molecular Iodine through the Use of a 2-Aminophenyloxazoline-Based Bidentate-Chelation System
-
The cobalt-catalyzed chelation-assisted C-H iodination of aromatic amides using molecular iodine as an iodinating reagent is reported. The reaction is carried out in an atmosphere of air and uses Co(OAc)2·4H2O as an efficient catalys
- Kommagalla, Yadagiri,Chatani, Naoto
-
supporting information
p. 5971 - 5976
(2019/08/26)
-
- Rhodium-Catalyzed Alkenylation of C-H Bonds in Aromatic Amides with Alkynes
-
The rhodium-catalyzed alkenylation of C-H bonds of aromatic amides with alkynes is reported. A variety of functional groups, including OMe, OAc, Br, Cl, and even NO2, are applicable to this reaction to give the corresponding hydroarylation prod
- Shibata, Kaname,Natsui, Satoko,Chatani, Naoto
-
supporting information
p. 2234 - 2237
(2017/05/12)
-
- PYRROLO-PYRROLE CARBAMATE AND RELATED ORGANIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF
-
The invention provides pyrrolo-pyrrole carbamate and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., solid tumor cancer, obesity, Down's syndrome, Alzheimer's disease, or pain, in a patient. The octahydropyrrolo pyrrole carbamates could be derived from hexafluoroisopropanol, Ν,Ν-disuccinimide and such. The activity of carbamates in MAGL, FAAH, and ABHD6 assays are also described.
- -
-
Paragraph 00726; 00727
(2015/01/16)
-
- DIFLUOROMETHYLENE COMPOUND
-
The present invention relates to a compound having an URAT1 inhibitory activity, and to an URAT1 inhibitor, a blood uric acid level-reducing agent and a pharmaceutical composition containing the compound. More specifically, the present invention relates to a compound represented by the formula (I): wherein R1 is -Q1-A1 or the like; R2 is a hydrogen atom, a halogen atom, a lower alkyl group or the like; W1, W2, W3 and W4 are each independently a nitrogen atom or a methine group optionally having substituents, or the like; X and Y are each a single bond, an oxygen atom or the like; Z is a hydroxyl group or COOR3 or the like.
- -
-
Paragraph 0505-0507
(2015/06/16)
-
- TETRAZOLINONE COMPOUND AND USE THEREOF
-
The compound represented by formula (1): wherein R4 and R5 each represents a hydrogen atom, a halogen atom, or a C1-C3 alkyl group; R6 represents a C1-C4 alkyl group, a C3-C6 cycloalkyl group, or the like; R7, R8, and R9 each represents a hydrogen atom, a halogen atom, or the like; R10 represents a C1-C3 alkyl group, or the like; R13 represents a C1-C3 alkyl group, or the like; and Q represents a phenyl group, or the like; has an excellent control effect on pests.
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-
Paragraph 0790
(2015/11/16)
-
- Pharmaceutical compositions comprising (3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol
-
Disclosed herein is a pharmaceutical composition comprising (3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl)methanol and methods of using the composition to treat chronic pain.
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-
Page/Page column 2; 3
(2015/12/05)
-
- TETRAZOLINONE COMPOUND AND APPLICATIONS THEREOF
-
Disclosed is a tetrazolinone compound having a high pest control effect and represented by the formula (1): wherein R1, R2, R3, and R11 each represent a halogen atom, a C1-C6 alkyl group, or the like; R4 and R5 each represent a hydrogen atom, a halogen atom, a C1-C3 alkyl group, or the like; R6 represents a C1-C3 alkyl group which may have a halogen atom(s) or the like; R7, R8, and R9 each represent a hydrogen atom, a halogen atom, or the like; R10 represents a C1-C3 alkyl group or the like; R12 represents a C1-C6 alkyl group, a C3-C6 cycloalkyl group, or the like, and R13 represents a C1-C6 alkyl group, a C2-C6 alkenyl group, or the like.
- -
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Paragraph 0757
(2015/11/24)
-
- APOPTOSIS-INDUCED AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
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Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-xL protein.
- -
-
Paragraph 1063
(2013/04/24)
-
- CYCLIC AMIDE DERIVATIVE
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Provided is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. (In the formula, A is C6-10 arylene, etc.; R1a, R1b and R1c each independently is a hydrogen atom, a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, etc.; R2 is an optionally substituted C6-10 aryl group, an optionally substituted 5- to 12-membered monocyclic or polycyclic heteroaryl group, an optionally substituted C7-16 aralkyl group, etc.; m is 0, etc.; n is an integer of 0 to 2.)
- -
-
Paragraph 0311; 0312; 0313
(2013/07/25)
-
- TETRAZOLINONE COMPOUNDS AND ITS USE AS PESTICIDES
-
The present invention provides a compound having an excellent efficacy for controlling pests. A tetrazolinone compound of a formula (1): [wherein R1 represents an C6-C16 aryl group, an C1-C12 alkyl group, or a C3-C12 cycloalkyl group, etc., which each optionally be substituted; R2, R3, R4 and R5 represent independently of each other a hydrogen atom, a halogen atom or an C1-C3 alkyl group, etc.; R6 represents an C1-C6 alkyl group, a C3-C6 cycloalkyl group, a halogen atom, a C1-C6 haloalkyl group, an C2-C6 alkenyl group, an C1-C6 alkoxy group, or a C1-C6 haloalkoxy group, etc.; R7, R8 and R9 represent independently of each other a hydrogen atom, a halogen atom, or an C1-C4 alkyl group, etc.; X represents an oxygen atom or a sulfur atom; and R10 represents an C1-C6 alkyl group, etc.] shows an excellent controlling efficacy on pests.
- -
-
Page/Page column 901
(2013/11/18)
-
- TETRAZOLINONE COMPOUNDS AND ITS USE
-
The present invention provides a compound having an excellent efficacy for controlling pests. A tetrazolinone compound of a formula (1): [wherein, R1 represents an C6-C16 aryl group, an C1-C12 alkyl group, a C3-C12 cycloalkyl group or an adamantyl group, etc., which each optionally be substituted; R2 represents a hydrogen atom, an C1-C12 alkyl group, or a halogen atom, etc.; R4 and R5 represent independently of each other a hydrogen atom or an C1-C3 alkyl group, etc.; R6, R7, R8 and R9 represent independently of each other a hydrogen atom, a halogen atom, an C1-C12 alkyl group, a C1-C12 haloalkyl group, an C2-C12 alkenyl group, a C3-C12 cycloalkyl group, an C1-C12 alkoxy group or a C1-C12 haloalkoxy group, etc.; X and Y represent independently of each other a sulfur atom or an oxygen atom; Q represents an oxygen atom or a sulfur atom; and R10 represents an C1-C6 alkyl group, etc.] shows an excellent controlling efficacy on pests.
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-
Paragraph 0452
(2013/11/18)
-
- FUSED PYRAZINE DERIVATIVES AS KINASE INHIBITORS
-
A series of quinoxaline derivatives, and analogues thereof, which are functionalised further by a substituted phenyl or pyridinyl moiety, being selective inhibitors of PO kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.
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Page/Page column 39
(2010/06/11)
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- 4-(1-(3-(HYDROXYMETHYL)-2-METHYLPHENYL)ETHYL)-1H-IMIDAZOLE-2(3H)-THIONE
-
Disclosed herein is 4-(1-(3-(hydroxymethyl)-2-methylphenyl)ethyl)-1H-imidazole-2(3H)-thione and methods of using the compound to treat chronic pain.
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-
Page/Page column 2; 10
(2010/09/03)
-
- DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS
-
The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
- -
-
-
- BTK protein kinase inhibitors
-
This application discloses pyridine and pyrimidine compounds according to formula I wherein R1, R2, R3, R4, R5, X1 and A are as described herein which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of formula I and at least one carrier, diluent or excipient.
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-
Page/Page column 58
(2009/05/29)
-
- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
-
The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.
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-
Page/Page column 50
(2009/08/18)
-
- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
-
The present invention is directed to novel compounds of Formula (I), pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of/and or prophylaxis of respiratory diseases, including antiinflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
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-
Page/Page column 52
(2009/08/16)
-
- Isoindolinone ureas: A novel class of KDR kinase inhibitors
-
A series of substituted isoindolinone ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 14c, are potent inhibitors of KDR both enzymatically (50nM) and cellularly (≤100nM). A 3D KDR/CDK2/MAP kinase overlay model with several structurally related tyrosine kinase inhibitors was used to predict the binding interactions of the isoindolinone ureas with the KDR active site.
- Curtin, Michael L.,Frey, Robin R.,Heyman, H. Robin,Sarris, Kathy A.,Steinman, Douglas H.,Holmes, James H.,Bousquet, Peter F.,Cunha, George A.,Moskey, Maria D.,Ahmed, Asma A.,Pease, Lori J.,Glaser, Keith B.,Stewart, Kent D.,Davidsen, Steven K.,Michaelides, Michael R.
-
p. 4505 - 4509
(2007/10/03)
-