- COMBINATION THERAPY FOR TREATING MPS1
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The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.
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Paragraph 0603; 0611-0613; 0614-0616
(2021/08/14)
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- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
- Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
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p. 194 - 200
(2019/09/13)
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- Apoptosis signal regulating kinase inhibitor and application thereof
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The invention discloses an apoptosis signal regulating kinase inhibitor and an application thereof. The apoptosis signal regulating kinase inhibitor is a compound represented by general formula I, anda tautomer or a pharmaceutically acceptable salt thereo
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Paragraph 0041-0044
(2020/05/01)
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- Substrate Profiling of the Cobalt Nitrile Hydratase from Rhodococcus rhodochrous ATCC BAA 870
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The aromatic substrate profile of the cobalt nitrile hydratase from Rhodococcus rhodochrous ATCC BAA 870 was evaluated against a wide range of nitrile containing compounds (>60). To determine the substrate limits of this enzyme, compounds ranging in size from small (90 Da) to large (325 Da) were evaluated. Larger compounds included those with a biaryl axis, prepared by the Suzuki coupling reaction, Morita–Baylis–Hillman adducts, heteroatomlinked diarylpyridines prepared by Buchwald–Hartwig crosscoupling reactions and imidazo[1,2a]pyridines prepared by the Groebke–Blackburn–Bienaymé multicomponent reaction. The enzyme active site was moderately accommodating, accepting almost all of the small aromatic nitriles, the diarylpyridines and most of the biaryl compounds and Morita–Baylis–Hillman products but not the Groebke–Blackburn–Bienaymé products. Nitrile conversion was influenced by steric hindrance around the cyano group, the presence of electron donating groups (e.g., methoxy) on the aromatic ring, and the overall size of the compound.
- Mashweu, Adelaide R.,Chhiba‐Govindjee, Varsha P.,Bode, Moira L.,Brady, Dean
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- Trash to treasure: Eco-friendly and practical synthesis of amides by nitriles hydrolysis in WepPA
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The hydration of nitriles to amides in a water extract of pomelo peel ash (WEPPA) was realized with moderate to excellent yields without using external transition metals, bases or organic solvents. This reaction features a broad substrate scope, wide functional group tolerance, prominent chemoselectivity, and good reusability. Notably, a magnification experiment in this bio-based solvent at 100 mmol further demonstrated its practicability.
- Sun, Yajun,Jin, Weiwei,Liu, Chenjiang
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supporting information
(2019/11/11)
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- POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
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Page/Page column 53; 54
(2018/07/29)
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- On the Synthesis and Reactivity of 2,3-Dihydropyrrolo[1,2- a ]quinazolin-5(1 H)-ones
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An improved, scalable synthetic route to the quinazolinone natural product 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one is reported. The applicability of this method to analogue synthesis and the synthesis of related natural products is explored. Finally, reactivity of the scaffold to a variety of electrophilic reagents, generating products stereoselectively, is reported.
- Sutherell, Charlotte L.,Ley, Steven V.
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p. 135 - 144
(2016/12/24)
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- Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases
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Tankyrases (TNKSs), members of the PARP (Poly(ADP-ribose)polymerases) superfamily of enzymes, have gained interest as therapeutic drug targets, especially as they are involved in the regulation of Wnt signalling. A series of 2-arylquinazolin-4-ones with varying substituents at the 8-position was synthesised. An 8-methyl group (compared to 8-H, 8-OMe, 8-OH), together with a 4′-hydrophobic or electron-withdrawing group, provided the most potency and selectivity towards TNKSs. Co-crystal structures of selected compounds with TNKS-2 revealed that the protein around the 8-position is more hydrophobic in TNKS-2 compared to PARP-1/2, rationalising the selectivity. The NAD+-binding site contains a hydrophobic cavity which accommodates the 2-aryl group; in TNKS-2, this has a tunnel to the exterior but the cavity is closed in PARP-1. 8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one was identified as a potent and selective inhibitor of TNKSs and Wnt signalling. This compound and analogues could serve as molecular probes to study proliferative signalling and for development of inhibitors of TNKSs as drugs.
- Nathubhai, Amit,Haikarainen, Teemu,Hayward, Penelope C.,Mu?oz-Descalzo, Silvia,Thompson, Andrew S.,Lloyd, Matthew D.,Lehti?, Lari,Threadgill, Michael D.
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p. 316 - 327
(2016/05/19)
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- THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
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Paragraph 0342; 0343
(2015/01/06)
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- BICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS
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The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
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- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases
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Page/Page column 49; 50
(2013/07/19)
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- A new protocol for the synthesis of primary, secondary and tertiary anthranilamides utilizing N-(2-aminoarylacyl)benzotriazoles
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A convenient route for efficient conversion of unprotected anthranilic acids into the corresponding N-(2-aminoarylacyl)benzotrazoles is described. N-(2-Aminoarylacyl)-benzotrazoles have been successfully used to synthesize primary, secondary and tertiary anthranilamides in high yields (71-96%). ARKAT-USA, Inc.
- Kaniskan, Nevin,Koekten, Sule,Celik, Ilhami
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p. 198 - 213
(2012/10/29)
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- Copper-catalyzed direct amination of ortho-functionalized haloarenes with sodium azide as the amino source
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A simple copper-catalyzed direct amination of ortho-functionalized haloarenes (2-halobenzoic acid, 2-halobenzamide, and N-(2-bromophenyl)acetamide derivatives) has been developed with use of NaN3 as the amino source in ethanol, and the corresponding ortho-functionalized aromatic amines were synthesized in good to excellent yields. The protocol undergoes one-pot Ullmann-type coupling of ortho-functionalized haloarenes with NaN3 to lead to ortho-functionalized azidoarenes, followed by reduction with ethanol.
- Zhao, Haibo,Fu, Hua,Qiao, Renzhong
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experimental part
p. 3311 - 3316
(2010/08/05)
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- Direct catalytic asymmetric synthesis of cyclic aminals from aldehydes
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A highly enantioselective Bronsted acid catalyzed direct synthesis of cyclic aminals from aldehydes has been developed. The methodology has been applied to the first asymmetric synthesis of several antihypertensive aminal drugs including (R)-Thiabutazide. Copyright
- Cheng, Xu,Vellalath, Sreekumar,Goddard, Richard,List, Benjamin
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supporting information; experimental part
p. 15786 - 15787
(2009/05/15)
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- Auto-redox reaction: Tin(II) chloride-mediated one-step reductive cyclization leading to the synthesis of novel biheterocyclic 5,6-dihydro-quinazolino[4,3-b]quinazolin-8-ones with three-point diversity
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A tin (II) chloride-mediated short, efficient, and practical regioselective synthesis of biheterocyclic 5,6-dihydro-quinazolino[4,3-b]quinazolin-8-ones with three-point diversity is reported. A one-step reductive transformation of 2-(2-nitro-phenyl)-3H-quinazolin-4-one in various alcohols furnished the desired tetracyclic product in good yields with high purity.
- Roy, Abhijeet Deb,Subramanian, Arunachalam,Roy, Raja
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p. 382 - 385
(2007/10/03)
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- PHARMACEUTICAL COMPOUNDS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
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Disclosed are 1-arylamino-phthalazines, 4-arylamino-benzo[d][1,2,3]triazines, and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
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Page/Page column 51
(2008/06/13)
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- Synthesis and structure-activity relationship of diarylamide derivatives as selective inhibitors of the proliferation of human coronary artery smooth muscle cells
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A series of diarylamide derivatives were synthesized and evaluated for their inhibitory activities against human coronary artery smooth muscle cells (SMCs) and human coronary artery endothelial cells (ECs). Compound 2w was superior to the lead compound, Tranilast, in terms of the potency of the activity and cell selectivity.
- Gita, Haruhisa,Sobe, Yoshiaki,Akaku, Haruo,Ekine, Rena,Oto, Yuso,Isawa, Satoru,Hayashi, Hideya
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p. 549 - 551
(2007/10/03)
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- Synthesis of Some New 4-Quinazolinone-2-carboxy Esters, 2-Carboxamides, 2-Carboxyhydrazides and Their Tosyl Derivatives Having Potential Biological Activity
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Some new 2-carbethoxy-3,4-dihydro-4-oxoquinazolines (II) and their derivatives such as 2-carboxamides (III), carboxyhydrazides (IV) and the tosylhydrazides (V) have been synthesized.The antitubercular activity of IV has been determined.
- Joshi, Vidya,Chaudhari, Rajendra P.
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p. 602 - 604
(2007/10/02)
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