- Guanidine derivative and application thereof
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The invention relates to a guanidine derivative serving as a VAP-1 inhibitor and application of the guanidine derivative, and further relates to a pharmaceutical composition containing the compound. The compound or the pharmaceutical composition can be us
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Paragraph 0307; 0309-0312
(2020/06/09)
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- NOVEL HETEROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS
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The present invention relates to novel compounds of the general formula (I) their tautomeric forms, their enantiomers, their diastereoisomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment or prevention of cancer and inflammatory diseases associated with Interleukin-1 Receptor Associated Kinase (IRAK), and more particularly compounds that modulate the function of IRAK4.
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Page/Page column 33
(2019/06/23)
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- FGFR4 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Provided are a class of compounds as shown in formula (I) as FGFR4 inhibitors, and pharmaceutically acceptable salts thereof, preparation methods therefor and the use thereof in the preparation of drugs for treating FGFR4-related diseases.
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Paragraph 0412-0413
(2019/10/10)
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- Tetrahydroisoquinoline compound and its preparation method, pharmaceutical composition and use
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The invention relates to a tetrahydroisoquinoline compound and its preparation method, pharmaceutical composition and use. The tetrahydroisoquinoline compound is shown by the general formula (1). In the general formula (1), the symbols have the same definitions as in the specification.
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
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Page/Page column 157
(2018/06/30)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
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Page/Page column 157
(2017/09/02)
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- Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core
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New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (~2 to 50 nM), MMP-13 (~2 to 50 nM), and MMP-14 (~4 to 60 nM). Additionally these compounds are selective to intermediate- and deep-pocket MMPs but not shallow-pocketed MMPs (e.g., MMP-1, ~850 to >50 000 nM; MMP-7, ~4000 to >25 000 nM). Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S,4R)-stereochemistry was optimal for all of the MMPs tested. However, in our newest compounds an interesting shift of preference to the trans form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility. We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.
- Jin, Yonghao,Roycik, Mark D.,Bosco, Dale B.,Cao, Qiang,Constantino, Manuel H.,Schwartz, Martin A.,Sang, Qing-Xiang Amy
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p. 4357 - 4373
(2013/07/19)
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- N -phosphonocarbonylpyrrolidine derivatives of guanine: A new class of Bi-substrate inhibitors of human purine nucleoside phosphorylase
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A complete series of pyrrolidine nucleotides, (3R)- and (3S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acids and (3S,4R)-, (3R,4S)-, (3S,4S)-, and (3R,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N- ylcarbonylphosphonic acids, were synthesized and e
- Rejman, Dominik,Panova, Natalya,Klener, Pavel,Maswabi, Bokang,Pohl, Radek,Rosenberg, Ivan
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experimental part
p. 1612 - 1621
(2012/05/05)
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- CARBAPENEM ANTIBACTERIALS WITH GRAM-NEGATIVE ACTIVITY
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The present invention provides β-methyl carbapenem compounds and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such compounds and/or compositions. The invention includes administering an effective amount of a carbapenem compound or salt and/or prodrug thereof to a host in need of such a treatment.
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Page/Page column 117
(2012/01/06)
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- FUSED HETEROCYCLIC COMPOUND
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The present invention relates to a fused heterocyclic compound having the Formula 1, which is useful as a platelet aggregation inhibitor, a method for preparing the same, and a pharmaceutical composition for inhibiting platelet aggregation comprising the same.
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- Highly active organocatalysts for asymmetric anti-mannich reactions
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Lighten the load! A family of enantiopure 4-oxy-substituted 3-aminopyrrolidines arising from the enantioselective ring-opening of meso-3-pyrroline oxide have been developed as catalysts for the asymmetric, anti-selective Mannich reaction (see scheme; PMP=
- Martín-Rapún, Rafael,Fan, Xinyuan,Sayalero, Sonia,Bahramnejad, Mahboubeh,Cuevas, Félix,Pericàs, Miquel A.
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p. 8780 - 8783
(2011/09/15)
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- COMPOUNDS FOR TREATING DISORDERS MEDIATED BY METABOTROPIC GLUTAMATE RECEPTOR 5, AND METHODS OF USE THEREOF
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Provided herein are compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, psychiatric disorders, neuromuscular disorders, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds provided herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.
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Page/Page column 153
(2010/11/03)
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- SUBSTITUTED PYRROLIDINE AMIDES, THE PRODUCTION THEREOF, AND THE USE THEREOF AS MEDICATIONS
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The object of the present invention is novel substituted pyrrolidine amides of the general formula (I) in which D, L. E, G, J, M, L1, L2, R4, and R5 are defined as in the specification, the tautomers, enantiomers, diastereomers, mixtures, and salts thereof, particularly physiologically tolerated salts with inorganic or organic acids or bases having valuable properties.
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Page/Page column 26
(2010/05/13)
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- THIENO-PYRIDINE DERIVATIVES AS MEK INHIBITORS
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A series of thieno[2,3-6]pyridine derivatives, attached at the 2-position to a substituted anilino moiety, which are substituted in the 3-position by a carbonyl group linked to a pyrrolidin-1-yl ring which in turn forms part of a heteroatom-containing fus
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- Design of novel aminopyrrolidine factor Xa inhibitors from a screening hit
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Starting from a hit identified by focused screening, 3-aminopyrrolidine factor Xa inhibitors were designed. The binding mode as determined by X-ray structural analysis as well as the pharmacokinetic behaviour of selected compounds is discussed.
- Zbinden, Katrin Groebke,Anselm, Lilli,Banner, David W.,Benz, Joerg,Blasco, Francesca,Decoret, Guillaume,Himber, Jacques,Kuhn, Bernd,Panday, Narendra,Ricklin, Fabienne,Risch, Philippe,Schlatter, Daniel,Stahl, Martin,Thomi, Stefan,Unger, Robert,Haap, Wolfgang
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body text
p. 2787 - 2795
(2009/10/17)
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- MINERALOCORTICOID RECEPTOR ANTAGONISTS AND METHODS OF USE
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The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly congestive heart failure, hypertension, diabetic nephropathy, or chronic kidney disease, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
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Page/Page column 25
(2009/07/10)
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- AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel substituted aminocyclohexanes of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 42
(2008/06/13)
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- Cyclic amines
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The invention is concerned with cyclic amines of formula (I) wherein X1 to X3, Y1 to Y3, R1′, R1″ and n are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit coagulation factor Xa and can be used as medicaments and for treating diseases associated with coagulation factor Xa.
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Page/Page column 36
(2010/11/24)
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- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The application is directed to haloalkyl-substituted compounds of Formula (I), wherein R1, R1a, R2, R3, R4’ and E are as defined in the claims. The compounds are inhibitors of cysteine proteases, in p
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Page/Page column 50-51
(2010/02/11)
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- AMIDINO COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceu
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Page/Page column 48-49
(2010/02/09)
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- PEPTIDIC COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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- Cathepsin cysteine protease inhibitors
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This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of Cathepsins K and L. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
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- Treatment of parasitic diseases by inhibition of cysteine proteases of the papain superfamily
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The present invention relates to compounds and pharmaceutical compositions which inhibit proteases, such as cysteine proteases. In particular, the present invention relates to compounds and pharmaceutical compositions which inhibit cysteine proteases of the papain superfamily. The compounds and pharmaceutical compositions of the present invention are useful for treating diseases, particularly parasitic diseases, which are mediated by such proteases. In particular, the present invention relates to a method of treating malaria by inhibiting the cysteine protease falcipain.
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- Practical synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine
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Three synthetic methods for the preparation of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate in the synthesis of the novel quinolone antitumur agent, AG-7352, have been developed. By one route, an efficient and large-scale preparation of the chiral pyrrolidine could be achieved through resolution of (±)-1-Boc-3-benzylamino-4-hydroxypyrrolidine, which is prepared from either 3-pyrroline or 1,4-dichloro-2-butene.
- Tsuzuki, Yasunori,Chiba, Katsumi,Mizuno, Kazuhiro,Tomita, Kyoji,Suzuki, Kenji
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p. 2989 - 2997
(2007/10/03)
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- 2-6-diaminopurine precursors
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The present invention relates to compounds of formula (IV): STR1 wherein Ra and Rb each represent a hydrogen atom or together form an alkylidene group.
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- Samarium diiodide-induced radical cyclization of oxime ether connected with formyl group: Synthesis of 4-pyrimidinyl- and 4-purinylpyrrolidin-3-ol nucleoside analogues
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SmI2-induced 5-exo-trig radical cyclization of oxime ether intramolecularly connected with the formyl group was found to be particularly effective for preparing cyclic trans-amino alcohol in good chemical yield with a high degree of stereoselectivity. Its successful application to the synthesis of a novel class of 4-pyrimidinyl- and 4-purinylpyrrolidin-3-ol nucleoside analogues is also described.
- Miyabe, Hideto,Kanehira, Sayaka,Kume, Kaori,Kandori, Hiromi,Naito, Takeaki
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p. 5883 - 5892
(2007/10/03)
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- Methyloxime-substituted aminopyrrolidine: A new surrogate for 7-basic group of quinolone
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Novel fluoroquinolones containing oxime functionalized aminopyrrolidines have been synthesized. They were found to possess potent antibacterial activities both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Among these compounds, LB20277 (compound 12) showed the most favorable in vivo efficacy and pharmacokinetic profile in animals. Based on these promising results, LB20277 was selected as a candidate for further evaluation.
- Hong, Chang Yong,Kim, Young Kwan,Lee, Yong Hee,Kwak, Jin Hwan
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p. 221 - 226
(2007/10/03)
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- Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety
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Balanol is a potent protein kinase C (PKC) inhibitor that is structurally composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine ring. A number of balanol analogs in which the perhydroazepine moiety is replaced have been synthesized and their biological activities evaluated against both PKC and cAMP-dependent kinase (PKA). The results suggested that the activity and the isozyme/kinase selectivity of these compounds are largely related to the conformation about this nonaromatic structural element of the molecules.
- Lai, Yen-Shi,Mendoza, José S.,Jagdmann Jr., G. Erik,Menaldino, David S.,Biggers, Christopher K.,Heerding, Julia M.,Wilson, Joseph W.,Hall, Steven E.,Jiang, Jack B.,Janzen, William P.,Ballas, Lawrence M.
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p. 226 - 235
(2007/10/03)
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- Synthesis and structure-activity relationship of 7-(3'-amino-4'-methoxypyrrolidin-1'-yl)-1-cyclopropyl-6,8-difluoro-1,4 -dihydro-4-oxoquinoline-3-carboxylic acids
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A new series of quinolone derivatives 3a-l bearing 3-amino-4-methoxypyrrolidines of different configurations and chirality were synthesized and their antibacterial activities as well as some of their toxicological properties were examined. As predicted by our previous quantitative structure-activity relationships (QSAR) analysis of C-7 heterocyclic amine substituted quinolonecarboxylic acid antibacterial agents, these pyrrolidine derivatives showed higher in vitro and in vivo antibacterial activities against both gram-positive and gram-negative bacteria than the analogs bearing various 3-substituted azetidines. Furthermore, the amino and methoxy substituent groups on the pyrrolidine ring exhibited strong configurational and chiral effects on the in vitro and in vivo antibacterial activities of these compounds: (1) cis compounds showed higher antibacterial activities against most of the pathogens examined; (2) N-methylation of the 3-amino group on the pyrrolidine ring lowered in vitro but not in vivo antibacterial activities, particularly leading to superior in vivo anti-pseudomonal activity; (3) the (3'S,4'R)-derivative showed substantially higher activity that the (3'R,4'S)-one. These findings led to the selection of compound 3k for further evaluation as it possessed the highest in vivo antibacterial activity and no cytotoxicity.
- Okada,Sato,Tsuji,Tsushima,Nakai,Yoshida,Matsuura
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p. 132 - 138
(2007/10/02)
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