- MULTI-SUBSTITUTED PYRIDONE DERIVATIVES AND MEDICAL USE THEREOF
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The present invention relates to multi-substituted pyridone derivatives and therapeutic use thereof. In particular, the present invention relates to a compound of formula (I), a preparation method therefor, a pharmaceutical composition comprising the same, as well as use thereof as a tyrosine kinase inhibitor, in particular, use thereof in treating a disease associated with tyrosine kinase activity. Each substituent in the formula (I) is defined as in the specification.
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Paragraph 0254; 0259-0260
(2021/07/08)
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- Lenvatinib impurity as well as preparation method and application thereof
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The invention discloses a lenvatinib impurity as well as a preparation method and application thereof. The impurity is a compound as shown in a formula III which is described in the specification. Thecompound as shown in the formula III provided by the invention can be used as a reference substance for detecting related substances of lenvatinib, and is used for controlling the purity of a lenvatinib bulk drug or preparation.
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Paragraph 0030; 0037-0040
(2020/07/24)
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- NOVEL POLYMORPHS OF 4-[3-CHLORO-4-(N'-CYCLOPROPYL UREIDO)PHENOXY]-7-METHOXYQUINOLINE-6-CARBOXAMIDE, ITS SALTS AND PROCESS FOR THE PREPARATION THEREOF
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The present invention relates to novel polymorphs of 4-[3-chloro-4-(N'- cyclopropyl ureido) phenoxy]-7- methoxyquinoline- 6- carboxamide methanesulfonate represented by following structural formula-1a and process for preparation thereof. Further, the pres
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- PROCESS FOR THE PREPARATION OF LENVATINIB OR ITS SALTS THEREOF
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The present invention provides a process for the preparation of Lenvatinib or its salts thereof. The present invention also provides a crystalline form of Lenvatinib, which is characterized by the PXRD pattern as shown in figure 1. The present invention a
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Page/Page column 8; 9
(2019/05/30)
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- Thiazolidone derivative of lovatinib acid and application of thiazolidone derivative
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The invention discloses 4-[3-chlorine group-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinoline formyl thiazolone and application thereof. The structure conforms the general formula (I) (please see the specification of the formula), the effica
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Paragraph 0018-0020
(2019/11/21)
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- Synthetic method of anti-cancer drug lenvatinib
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The invention discloses a synthetic method of anti-cancer drug lenvatinib. Lenvatinib is synthesized from the compound p-aminosalicylic acid shown as drawing 1 as a starting material with the method.Reaction conditions are mild, special reaction equipment is not needed, and the applicable range is wider. Raw materials and reagents used in the method are easily purchased from the market, and reduction of production cost is facilitated. The method is simple to operate, short in synthesis period and more suitable for large-scale industrial production of lenvatinib. The method is high in synthesis efficiency, and purity of synthesized lenvatinib is high.
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Paragraph 0112; 0124-0127; 0160-0163; 0195-0198; 0231-0234
(2018/04/02)
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- TYROSINE KINASE INHIBITOR AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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The present invention relates to a tyrosine kinase inhibitor and a pharmaceutical composition comprising same. The tyrosine kinase inhibitor of the present invention has the structures as shown in the following formula (I) or (II):
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- Naphthamides as novel and potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: Design, synthesis, and evaluation
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A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.
- Harmange, Jean-Christophe,Weiss, Matthew M.,Germain, Julie,Polverino, Anthony J.,Borg, George,Bready, James,Chen, Danlin,Choquette, Deborah,Coxon, Angela,DeMelfi, Tom,DiPietro, Lucian,Doerr, Nicholas,Estrada, Juan,Flynn, Julie,Graceffa, Russell F.,Harriman, Shawn P.,Kaufman, Stephen,La, Daniel S.,Long, Alexander,Martin, Matthew W.,Neervannan, Sesha,Patel, Vinod F.,Potashman, Michele,Regal, Kelly,Roveto, Phillip M.,Schrag, Michael L.,Starnes, Charlie,Tasker, Andrew,Teffera, Yohannes,Wang, Ling,White, Ryan D.,Whittington, Douglas A.,Zanon, Roger
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p. 1649 - 1667
(2008/09/20)
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- Evaluation of a series of naphthamides as potent, orally active vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors
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We have previously shown N-arylnaphthamides can be potent inhibitors of vascular endothelial growth factor receptors (VEGFRs). N-Alkyl and N-unsubstituted naphthamides were prepared and found to yield nanomolar inhibitors of VEGFR-2 (KDR) with an improved selectivity profile against a panel of tyrosine and serine/threonine kinases. The inhibitory activity of this series was retained at the cellular level. Naphthamides 3, 20, and 22 exhibited good pharmacokinetics following oral dosing and showed potent inhibition of VEGF-induced angiogenesis in the rat corneal model. Once-daily oral administration of 22 for 14 days led to 85% inhibition of established HT29 colon cancer and Calu-6 lung cancer xenografts at doses of 10 and 20 mg/kg, respectively.
- Weiss, Matthew M.,Harmange, Jean-Christophe,Polverino, Anthony J.,Bauer, David,Berry, Loren,Berry, Virginia,Borg, George,Bready, James,Chen, Danlin,Choquette, Deborah,Coxon, Angela,DeMelfi, Tom,Doerr, Nicholas,Estrada, Juan,Flynn, Julie,Graceffa, Russell F.,Harriman, Shawn P.,Kaufman, Stephen,La, Daniel S.,Long, Alexander,Neervannan, Sesha,Patel, Vinod F.,Potashman, Michele,Regal, Kelly,Roveto, Phillip M.,Schrag, Michael L.,Starnes, Charlie,Tasker, Andrew,Teffera, Yohannes,Whittington, Douglas A.,Zanon, Roger
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p. 1668 - 1680
(2008/12/22)
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- COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
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Page/Page column 48
(2010/11/24)
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- Nitrogen-containing aromatic derivatives
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Compounds represented by the following general formula: [wherein Ag is an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xg is —O—, —S—, etc.; Yg is an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tg1 is a group represented by the following general formula: (wherein Eg is a single bond or —N(Rg2)—, Rg1 and Rg2 each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, etc. and Zg represents a C1-8 alkyl group, a C3-8 alicyclic hydrocarbon group, a C6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.
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- Quinoline derivatives inhibiting the effect of growth factors such as VEGF
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Compounds of the formula (I): wherein: R2represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; n is an integer from 0 to 5; Z represents —O—, —NH—, —S— or —CH2—; G1represents phenyl or a 5-10 membered heteroaromatic cyclic or bicyclic group; Y1, Y2, Y3and Y4each independently represents carbon or nitrogen; R1represents fluoro or hydrogen; m is an integer from 1 to 3; R3represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR4R5(wherein R4and R5, can each be hydrogen or C1-3alkyl), or a group R6—X1— wherein X1represents —CH2— or a heteroatom linker group and R6is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R6is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans, processes for the preparation of such derivatives, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
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Page column 67
(2010/02/08)
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- Quinoline derivatives as tyrosine kinase inhibitors
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The invention concerns quinoline derivatives of formula (I) wherein n is 0-3 and each R4, which may be the same or different, is a substituent such as halogeno, hydroxy, amino, nitro, trifluoromethyl, trifluoromethoxy, cyano or (1-6C)alkyl, or
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