- PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER
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There are provided compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers. (I)
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Paragraph 00189-00190
(2021/03/05)
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- GLYCYRRHETINIC ACID DERIVATIVES FOR USE IN TREATING HYPERKALEMIA
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The present invention provides a compound of formula (I) or a salt thereof: (F ormula (I)) wherein X, L, V, R1, R2, R3 and R4, are as defined herein. The claimed compounds inhibit the enzyme 11-hydroxysteroid de
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Page/Page column 179
(2020/08/22)
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- DERIVATIVES OF RELEBACTAM AND USES THEREOF
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Derivatives of relebactam, therapeutic methods of using the derivatives of relebactam, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The derivatives of relebactam are suitable for oral administration.
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Paragraph 1364-1366; 1766-1767
(2020/04/24)
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- Influenza virus replication inhibitors and uses thereof (by machine translation)
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The invention provides a compound as an influenza virus replication inhibitor, a method for preparing the same, a pharmaceutical composition containing the compound and application. (by machine translation)
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Paragraph 0742; 0744-0746
(2019/10/01)
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- Coupling of an Acyl Migration Prodrug Strategy with Bio-activation to Improve Oral Delivery of the HIV-1 Protease Inhibitor Atazanavir
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HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats. This strategy was refined by conjugating the amine with a promoiety designed to undergo bio-activation, as a means of modulating the subsequent chemo-activation. This culminated in a lead prodrug that (1) yielded substantially better oral drug delivery of 1 when compared to the parent itself, the simple acyl migration-based prodrug, and the corresponding simple l-Val prodrug, (2) acted as a depot which resulted in a sustained release of the parent drug in vivo, and (3) offered the benefit of mitigating the pH-dependent absorption associated with 1, thereby potentially reducing the risk of decreased bioavailability with concurrent use of stomach-acid-reducing drugs.
- Subbaiah, Murugaiah A. M.,Meanwell, Nicholas A.,Kadow, John F.,Subramani, Lakshumanan,Annadurai, Mathiazhagan,Ramar, Thangeswaran,Desai, Salil D.,Sinha, Sarmistha,Subramanian, Murali,Mandlekar, Sandhya,Sridhar, Srikanth,Padmanabhan, Shweta,Bhutani, Priyadeep,Arla, Rambabu,Jenkins, Susan M.,Krystal, Mark R.,Wang, Chunfu,Sarabu, Ramakanth
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p. 4176 - 4188
(2018/05/23)
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- Tetrahydrocyclopentapyrrole derivative and preparation method therefor
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The purpose of the present invention is to provide: a tetrahydrocyclopentapyrrole derivative capable of being used for preventing or treating a peptic ulcer gastritis or reflux esophagitis; a preparation method therefor; and a pharmaceutical composition containing the same.
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Paragraph 0745; 0746; 0747; 0748
(2016/10/08)
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- Pharmaceutical composition for the treatment or prevention of stroke and systemic embolism
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The present invention relates to a prodrug useful for treating or preventing a stroke and systemic embolism and suitable for being effectively used in the oral delivery of dabigatran, and to a compound represented by chemical formula 1, a pharmaceutically acceptable salt thereof, and a hydrate thereof or a solvate thereof. The compound represented by the chemical formula 1, the pharmaceutically acceptable salt thereof, and the hydrate thereof or the solvate thereof are useful for treating or preventing a stroke and systemic embolism, and is suitable for being effectively used in oral delivery since the absorption rate, that is, bioavailability of dabigatran is improved.(AA) DSC curve of dabigatran pivoxyl (+)-(1S)- campo-10-sulfonateCOPYRIGHT KIPO 2015
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Paragraph 0532-0536
(2016/11/17)
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- N-SUBSTITUTED-CYCLIC AMINO DERIVATIVE
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The present invention provides a compound of formula (I): wherein R1a is optionally substituted C1-6 alkyl, etc.; R1m is hydrogen atom, etc.; G1, G2, G3 and G4 are (i), etc. ((i) G1 is -N(R1b)-, G2 is -CO-, G3 is -C(R1c)(R1d)-, and G4 is oxygen, etc.); R1b is optionally substituted C1-6 alkyl, etc.; R1c and R1d are each independently optionally substituted C1-6 alkyl, etc.; R2 is optionally substituted C1-6 alkyl, etc.; R3a, R3b, R3c, and R3d are each independently a group: -A-B (A is a single bond, etc., B is hydrogen atom, etc.), etc.; n is 1, etc.; R5 is C1-4 alkoxycarbonyl, etc., or a pharmaceutically acceptable salt thereof, which is useful as a renin inhibitor.
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Page/Page column 159
(2012/05/20)
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- NITROGEN CONTAINING HETEROAROMATICS AS FACTOR Xa INHIBITORS
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The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula (I) or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is N or NH and D may be C(=NH)NH2, which are useful as inhibitors of factor Xa.
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Page/Page column 78
(2009/10/01)
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- 9-Aminocarbonylsubstituted derivatives of glycylcyclines
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This invention provides compounds of Formula I having the structure where R1, R2, R3 and A are defined in the specification or a pharmaceutically acceptable salt thereof useful as antibacterial agents. Compounds according
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Page/Page column 47
(2010/11/26)
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- Prodrugs for amidines: Synthesis and anti-Pneumocystis carinii activity of carbamates of 2,5-bis(4-amidinophenyl)furan
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Syntheses of several carbamate analogues of 2,5-bis(4- amidinophenyl)furan (1) under mild conditions and their evaluation as prodrugs against Pneumocystis carinii pneumonia (PCP) in an immunosuppressed rat model are described. Thus, nine new bis-carbamates: methoxycarbonyl (2), 2,2,2-trichloroethoxycarbonyl (3), ethylthiocarbonyl (4), benzyloxycarbonyl (5), (4-methyl-2-oxo-1,3-dioxol-4-en-5-yl)methoxycarbonyl (6), phenoxycarbonyl (7), 4-fluorophenoxycarbonyl (8), 4-methoxyphenoxycarbonyl (9), and (1-acetoxy)ethoxycarbonyl (10) and a biscarbonate ethoxycarbonyloxy (1) of the bis-amidine 1 have been synthesized and evaluated. The in vivo results show that the 4-fluorophenyl carbamate 8 and the 4-methoxyphenyl carbamate 9 in this series had the best anti-PCP activity by both intravenous and oral administration at a dosage level of 22 mol and 33 μmol/kg/day, respectively. Compounds 3-7 were also more active than the parent drug (1) on oral administration. The acute toxicity usually exhibited by the parent amidine 1 at a dosage level of 22 μmol/kg/day on intravenous administration has been significantly reduced by the prodrug modifications, with the exception of compound 10 which exhibited some toxicity. This report also describes the synthesis of several aryl-alkyl and aryl-aryl carbonates (12- 14, 16-23) as efficient reagents for the preparation of carbamate derivatives from bis-arylamidines.
- Rahmathullah, Syed M.,Hall, James Edwin,Bender, Brendan C.,McCurdy, Donald R.,Tidwell, Richard R.,Boykin, David W.
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p. 3994 - 4000
(2007/10/03)
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- Investigation of (oxodioxolenyl)methyl carbamates as nonchiral bioreversible prodrug moieties for chiral amines
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The preparation of(oxodioxolenyl)methyl carbamates and their evaluation as novel nonchiral prodrug moieties for chiral primary and secondary amino functional drugs are described. 4-(Carbamoylmethyl)-2-oxo-1,3-dioxolene derivatives of 3,4-dimethoxyphenethy
- Alexander, Jose,Bindra, Dilbir S.,Glass, Joan D.,Holahan, Marie A.,Renyer, Mara L.,Rork, Gerald S.,Sitko, Gary R.,Stranieri, Maria T.,Stupienski, Raymond F.,Veerapanane, Hemalata,Cook, Jacquelynn J.
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p. 480 - 486
(2007/10/03)
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- Dioxolenylmethyl carbamates pro moieties for amine drugs
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This invention relates to a the use of new oxodioxolenylmethyl carbamates to produce bioreversible neutral prodrugs from primary and secondary amines.
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