- NOVEL FUNCTIONALIZED LACTAMS AS MODULATORS OF THE 5-HYDROXYTRYPTAMINE RECEPTOR 7 AND THEIR METHOD OF USE
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Described herein are new, selective modulators of the 5 -HT7 receptor. These selective compounds can be useful for the treatment of CNS and non-CNS indications. Compounds described herein can be selective in targeting 5-HT7 receptors
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Paragraph 000723
(2021/05/21)
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- Synthesis of optically active (R)- And (S)-β-arginine from pyroglutamic acid
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– The first synthesis of optically active β-arginine was achieved starting from commercially available pyroglutamic acid. The new synthetic protocol is characterized by the use of nitrile as a carboxylic acid surrogate which could be transformed to the co
- Yasuno, Yoko,Sawai, Akira,Sekihara, Ai,Shinada, Tetsuro
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p. 165 - 176
(2020/02/04)
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- NOVEL FUNCTIONALIZED LACTAMS AS MODULATORS OF THE 5-HYDROXYTRYPTAMINE RECEPTOR 7 AND THEIR METHOD OF USE
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Pharmaceutical compositions of the invention comprise functionalized lactam derivatives of formula (I) having a disease-modifying action in the treatment of diseases associated with dysregulation of 5- hydroxytryptamine receptor 7 activity. A is selected
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Paragraph 01130
(2019/11/28)
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- HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF DISEASE
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Described herein are heterocyclic compounds, compositions, and methods for their use for the treatment of disease.
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Paragraph 00217
(2017/06/01)
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- MUSCARINIC AGONISTS
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This invention relates to compounds that are agonists of the muscarinic M4 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula 1a or a salt thereof, wherein n, p, Q, R1, R2, R3, R9 and R4 are as defined herein.
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Page/Page column 45
(2017/02/28)
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- Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis
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Idiopathic pulmonary fibrosis (IPF) is a serious and deadly disease for which treatment options are limited. The recent approval of antifibrosis agent nintedanib represents one of the first therapeutic approaches for the treatment of IPF. Here, we report novel indolinone-based multikinase inhibitors that target angiogenesis and fibrosis pathways and may serve as potential therapeutics for IPF. KBP-7018 is a novel, tyrosine kinase-selective inhibitor with potent effects on three fibrotic kinases (c-KIT, PDGFR, and RET). The pharmacokinetics (PK) properties of KBP-7018 were favorable in mice, rats, and dogs. In a bleomycin (BLM)-induced mouse pulmonary fibrosis model, 10, 30, and 100 mg/kg daily doses (q.d.) of KBP-7018 improved the 28-day survival rate in a dose-dependent manner. The improved efficacy of KBP-7018 compared to nintedanib provided a certain level of chemical validation for the involvement of PDGFR, c-KIT, and RET in IPF. Thus, KBP-7018 represents a novel multikinase inhibitor with differentiated activity, highly enhanced selectivity, and acceptable PK profiles that will enter phase I clinical trials.
- Huang, Zhenhua,Li, Heran,Zhang, Qian,Lu, Fangzheng,Hong, Mei,Zhang, Zhigang,Guo, Xiaocui,Zhu, Yuanju,Li, Sanming,Liu, Hongzhuo
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supporting information
p. 1142 - 1147
(2017/11/15)
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- CARBAZOLE-CONTAINING AMIDES, CARBAMATES, AND UREAS AS CRYPTOCHROME MODULATORS
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The subject matter herein is directed to carbazole-containing amide, carbamate, and urea derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, D, E, G, J, L, M, Q, a, and b are accordingly described. Also provided are pharmaceutical compositions containing the compounds of formula I to treat a Cry-mediated disease or disorder, such as diabetes, complications associated with diabetes, Cushing's syndrome, NASH, NAFLD, asthma, and COPD.
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Paragraph 0360
(2015/10/28)
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- NOVEL AMIDE DERIVATIVE AND USE THEREOF AS MEDICINE
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Provided are a novel low-molecular-weight compound that suppresses production of induction type MMPs, particularly MMP-9, rather than production of hemostatic type MMP-2, as well as a prophylactic/therapeutic drug for autoimmune diseases or osteoarthritis. An amide derivative represented by the following formula (I) wherein each symbol is as defined in the specification, or a pharmacologically acceptable salt thereof.
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Paragraph 0804; 0805; 0806
(2013/03/26)
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- NEW COMPOUNDS
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The invention relates to new naphthyridine derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
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Page/Page column 155
(2013/05/21)
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- ANTICANCER PYRIDOPYRAZINES VIA THE INHIBITION OF FGFR KINASES
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The invention relates to new pyridopyrazine derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
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Page/Page column 145
(2013/05/21)
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- Novel synthesis of CP-734432, an EP4 agonist, using Sharpless asymmetric dihydroxylation
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A novel and efficient asymmetric route to CP-734432, a lactam analog of PGE2, that shows selective agonism against the EP4 receptor subtype, is reported herein. The key steps include a Heck coupling to introduce the aryl ring at C-16 and a highly diastere
- Nair, Sajiv K.,Matthews, Jean J.,Cripps, Stephan J.,Ma, Chunrong,Dovalsantos, Elena Z.,Grubbs, Alan W.,Sach, Neal W.,Hoeve, Wolter ten,Koster, Han,Flahive, Erik J.,Tanis, Steven P.,Renner, Matt,Wiltenburg, Jim van
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body text
p. 1451 - 1454
(2010/04/29)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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Disclosed herein are compounds of formula (I) wherein R1, R2, R3, R25a, R26a, X, and n are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and pharmaceutical compositions are also described
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- Design of HIV-1 protease inhibitors with pyrrolidinones and oxazolidinones as novel P1′-ligands to enhance backbone-binding interactions with protease: Synthesis, biological evaluation, and protein-ligand X-ray studies
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Structure-based design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors are described. In an effort to enhance interactions with protease backbone atoms, we have incorporated stereochemically defined methyl-2-pyrrolidinone and methyl oxazolidinone as the P1′-ligands. These ligands are designed to interact with Gly-27′ carbonyl and Arg-8 side chain in the S1′-subsite of the HIV protease. We have investigated the potential of these ligands in combination with our previously developed bis-tetrahydrofuran (bis-THF) and cyclopentanyltetrahydrofuran (Cp-THF) as the P2-ligands. Inhibitor 19b with a (R)-aminomethyl-2-pyrrolidinone and a Cp-THF was shown to be the most potent compound. This inhibitor maintained near full potency against multi-PI-resistant clinical HIV-1 variants. A high resolution protein-ligand X-ray crystal structure of 19b-bound HIV-1 protease revealed that the P1′-pyrrolidinone heterocycle and the P2-Cp-ligand are involved in several critical interactions with the backbone atoms in the S1′ and S2 subsites of HIV-1 protease.
- Ghosh, Arun K.,Leshchenko-Yashchuk, Sofiya,Anderson, David D.,Baldridge, Abigail,Noetzel, Marcus,Miller, Heather B.,Tie, Yunfeng,Wang, Yuan-Fang,Koh, Yasuhiro,Weber, Irene T.,Mitsuya, Hiroaki
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experimental part
p. 3902 - 3914
(2010/01/06)
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- Selenium-promoted synthesis of enantiopure octahydroindolizines, hexahydro-1H-pyrrolizines and hexahydro-3H-pyrrolizin-3-ones
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Enantiomerically pure disubstituted pyrrolidines, recently synthesized from commercially available enantiomerically pure β-aminoalcohol, were used as starting materials to synthesize enantiomerically pure hexahydro-1H-pyrrolizines and octahydroindolizine through a cyclization reaction promoted by N-(phenylseleno)phthalimide. Similarly, starting from enantiopure 5-(hydroxymethyl)pyrrolidin-2-ones, enantiopure hexahydro-3H-pyrrolizin-3-ones were obtained.
- Tiecco, Marcello,Testaferri, Lorenzo,Bagnoli, Luana,Scarponi, Catalina
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scheme or table
p. 2411 - 2416
(2009/04/06)
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- BIARYL SUBSTITUTED HETEROCYCLE INHIBITORS OF LTA4H FOR TREATING INFLAMMATION
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The present invention relates to a chemical genus of biaryl substituted heterocycle inhibitors of LTA4H (leukotriene A4 hydrolase) useful for the treatment and prevention and prophylaxis of inflammatory diseases and disorders. The compounds have general formula Ψ: An example is
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Page/Page column 54
(2008/06/13)
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- 12. Approaches to the Synthesis of Cytochalasans; Part 9: A Versatile Concept Leading To All Structural Types of Cytochalasans
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Starting from D-glutamic acid (5), the bicyclic compounds 4a and 4b were synthesized via 17 (Schemes 1 and 2).The reaction leading to 4g and 4h with LiCuPh2 was not successful.But treatment of the N-protected model lactams 19, 21, and 22 with Li2Cu(CN)Ph2 gave the amino ketones 24, 26, and 26, respectively (Scheme 3).The desired compound 23 was obtained from 20.Conversion of the unprotected lactams 28, 31, and 32 gave the phenyl derivative 34 in excellent yields.Ester 35 was transformed to the α-amino-γ-oxo-acid derivative 36.This conversion opens a novel access to this type of compounds.
- Ackermann, Jean,Matthes, Michael,Tamm, Christoph
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p. 122 - 132
(2007/10/02)
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