- NOVEL TETRAZOLE COMPOUNDS AND THEIR USE IN THE TREATMENT OF TUBERCULOSIS
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The invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis.
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Page/Page column 83
(2019/03/05)
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- Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents
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Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.
- Xu, Xi,Ge, Raoling,Li, Lei,Wang, Jubo,Lu, Xiaoyu,Xue, Siqi,Chen, Xijing,Li, Zhiyu,Bian, Jinlei
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p. 1325 - 1344
(2017/11/13)
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- Proton pump inhibitors
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 2 , R 3 and R 4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R 5 and R 6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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Paragraph 0288
(2015/11/16)
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- SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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The present invention provides compounds of Formula (I): or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.
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Paragraph 00324
(2013/04/25)
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- Efficient indoles and anilines syntheses employing tert-butyl sulfinamide as ammonia surrogate
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tert-Butyl sulfinamide is an ammonia equivalent for the palladium-catalyzed amination of aryl bromides and aryl chlorides. Using these amine derivatives, it has been observed that indoles and anilines with sensitive functional groups can be readily prepared. This surrogate has also been used for the synthesis of indoles from 2-halophenols using palladium catalyzed cross coupling reaction as the key step.
- Prakash, Anjanappa,Dibakar, Mullick,Selvakumar, Kumaravel,Ruckmani, Kandasamy,Sivakumar, Manickam
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p. 5625 - 5628
(2011/11/06)
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- PYRIDONE AND PYRIDAZONE ANALOGUES AS GPR119 MODULATORS
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Novel compounds of structure Formula (I) or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein Z, R1, R2, R21, T1, T2, T3 and T4 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.
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Page/Page column 84
(2010/04/03)
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- Benzene, Pyridine, and Pyridazine Derivatives
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Disclosed are compounds and pharmaceutically acceptable salts of Formula I wherein A, Q1, Q2, Q3, R3, and R4 are as defined herein. Compounds of Formula I are useful in the treatment of diseases and/o
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Page/Page column 28
(2010/11/30)
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- DIPEPTIDE ANALOGS AS COAGULATION FACTOR INHIBITORS
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Disclosed are novel dipeptide analogs compounds of Formula (I), (II) or (III) or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a solvate, or a prodrug thereof, which are inhibitors of factor XIa and/or plasma kallikrein, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of thrombotic diseases.
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Page/Page column 145
(2009/01/23)
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- Thiazolyl-Dihydro-Indazole
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The present invention encompasses compounds of general formula (1) wherein R1 to R6 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use th
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Page/Page column 11
(2008/06/13)
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- PROTON PUMP INHIBITORS
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R2, R3 and R4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R5 and R6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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- GPCR AGONISTS
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Compounds of formula (I): or pharmaceutically acceptable salts thereof, are GPCR agonists and are useful as for the treatment of obesity and diabetes.
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Page/Page column 26-27
(2010/11/25)
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- DIARYLHYDANTOIN COMPOUNDS
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The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for syntheszing them and using them in the treatment of hormone refractory prostate cancer.
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Page/Page column 75
(2008/06/13)
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- PROTON PUMP INHIBITORS
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Proton pump inhibitors which have excellent proton pumping activity and which can be converted in vivo into proton pump inhibitors to exhibit antiulcer effect and so on, containing compounds represented by the general formula (I) or salts thereof or prodrugs of the same: (I) wherein X and Y are each independently a free valency or a spacer whose main chain has 1 to 20 carbon atoms; R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; R2, R3 and R4 are each independently hydrogen, an optionally substituted hydrocarbon group, optionally substituted thienyl, optionally substituted benzo[b]thienyl, optionally substituted furyl, optionally substituted pyridyl, optionally substituted pyrazolyl, optionally substituted pyrimidinyl, acyl, halogeno, cyano, or nitro; and R5 and R6 are each independently hydrogen or an optionally substituted hydrocarbon group.
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Page/Page column 153
(2010/10/20)
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- Exploiting subsite S1 of trypsin-like serine proteases for selectivity: Potent and selective inhibitors of urokinase-type plasminogen activator
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A nonselective inhibitor of trypsin-like serine proteases, 2-(2-hydroxybiphenyl-3-yl)-lH-indole-5-carboxamidine (1) (Verner, E.; Katz, B. A.; Spencer, J.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika. K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young, W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases1 that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine at the 6-position of the 5-amidinoindole P1 group on 1, generated up to 6700-fold selectivity toward the Ser190 enzymes and against the Alal90 enzymes. The larger chlorine atom displaces a water molecule (H2O1s1) that binds near residue 190 in all the complexes of 1, and related inhibitors, in uPA, thrombin, and trypsin. The water molecule, H2O1s1, in both the Ser190 or Ala190 enzymes, hydrogen bonds with the amidine N1 nitrogen of the inhibitor. When it is displaced, a reduction in affinity toward the Ala190 enzymes is observed due to the amidine N1 nitrogen of the bound inhibitor being deprived of a key hydrogen-bonding partner. In the Ser190 enzymes the affinity is maintained since the serine hydroxyl oxygen Oγser190 compensates for the displaced water molecule. Highresolution crystallography provided evidence for the displacement of the water molecule and validated the design rationale. In summation, a novel and powerful method for engineering selectivity toward Ser190 proteases and against Ala190 proteases without substantially increasing molecular weight is described.
- Mackman,Katz,Breitenbucher,Hui,Verner,Luong,Liu,Sprengeler
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p. 3856 - 3871
(2007/10/03)
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- SYNTHESIS AND SOME PROPERTIES OF 3-FLUORO-4-CYANOPHENYL 4 prime -n-ALKYLBENZOATES.
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A series of 3-fluoro-4-cyanophenyl 4 prime -n-alkylbenzoates, which show monotropic nematic phases, was prepared and their transition temperatures and melting enthalpies were measured. The 3-fluoro-4-cyanophenyl 4 prime -n-propylbenzoate, 3-chloro-4-cyanophenyl 4 prime -n-propylbenzoate and 4-cyanophenyl 4 prime -n-propylbenzoate were mixed with a nematic mixture (A) of 4-n-alkoxyphenyl 4 prime -n-alkylcyclohexane-1 prime -carboxylates. 3-Fluoro-4-cyanophenyl 4 prime -n-propylbenzoate decreases the N-I transition temperature less, increases the birefringence more, and increases the bulk viscosity less than 3-chloro-4-cyanophenyl 4 prime -n-propylbenzoate, and reduces the threshold voltage to the greatest extent. The dielectric anisotropies of 3-fluoro-4-cyanophenyl 4 prime -n-propylbenzoate and 4-cyanophenyl 4 prime -n-propylbenzoate determined from a series of solutions of the compounds in nematic mixture (A) are 35. 9 and 29. 6, respectively.
- Sasaki,Takeuchi,Sato,Takatsu
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p. 169 - 178
(2007/10/02)
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