US20050239852A1 - 2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors - Google Patents
2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors Download PDFInfo
- Publication number
- US20050239852A1 US20050239852A1 US10/523,018 US52301805A US2005239852A1 US 20050239852 A1 US20050239852 A1 US 20050239852A1 US 52301805 A US52301805 A US 52301805A US 2005239852 A1 US2005239852 A1 US 2005239852A1
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- US
- United States
- Prior art keywords
- methyl
- phenyl
- thiazol
- ylamino
- pyridin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Definitions
- the present invention relates to novel compounds selected from 2-(3-aminoaryl)amino-4-aryl-thiazoles that selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic, and degenerative disorders. More particularly, these compounds are potent and selective c-kit inhibitors.
- Tyrosine kinases are receptor type or non-receptor type proteins, which transfer the terminal phosphate of ATP to tyrosine residues of proteins thereby activating or inactivating signal transduction pathways. These proteins are known to be involved in many cellular mechanisms, which in case of disruption, lead to disorders such as abnormal cell proliferation and migration as well as inflammation.
- tyrosine kinases As of today, there are about 58 known receptor tyrosine kinases. Other tyrosine kinases are the well-known VEGF receptors et al., Nature 362, pp. 841-844, 1993), PDGF receptors, c-kit and the FLK family. These receptors can transmit signals to other tyrosine kinases including Src, Raf, Frk, Btk, Csk, Abl, Fes/Fps, Fak, Jak, Ack. etc.
- c-kit is of special interest. Indeed, c-kit is a key receptor activating mast cells, which have proved to be directly or indirectly implicated in numerous pathologies for which the Applicant filed WO 03/004007, WO 03/004006, WO 03/003006, WO 03/003004, WO 03/002114, WO 03/002109, WO 03/002108, WO 03/002107, WO 03/002106, WO 03/002105, WO 03/039550, WO 03/035050, WO 03/035049, U.S. 60/359,652 and U.S. 60/359651.
- mast cells present in tissues of patients are implicated in or contribute to the genesis of diseases such as autoimmune diseases (rheumatoid arthritis, inflammatory bowel diseases (IBD)) allergic diseases, tumor angiogenesis, inflammatory diseases, and interstitial cystitis.
- autoimmune diseases rheumatoid arthritis, inflammatory bowel diseases (IBD)
- IBD inflammatory bowel diseases
- mast cells participate in the destruction of tissues by releasing a cocktail of different proteases and mediators such as histamine, neutral proteases, lipid-derived mediators (prostaglandins, thromboxanes and leucotrienes), and various cytokines (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, TNF- ⁇ , GM-CSF, MIP-1a, MIP-1b, MIP-2 and IFN- ⁇ ).
- proteases and mediators such as histamine, neutral proteases, lipid-derived mediators (prostaglandins, thromboxanes and leucotrienes), and various cytokines (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, TNF- ⁇ , GM-CSF, MIP-1a, MIP-1b, MIP-2 and IFN- ⁇ ).
- the c-kit receptor also can be constitutively activated by mutations leading to abnormal cell proliferation and development of diseases such as mastocytosis and various cancers.
- the main objective underlying the present invention is therefore to find potent and selective compounds capable of inhibiting wild type and/or mutated c-kit.
- tyrosine kinase inhibitors for example, bis monocyclic, bicyclic or heterocyclic aryl compounds (WO 92/20642), vinylene-azaindole derivatives (WO 94/14808) and 1-cycloproppyl-4-pyridyl-quinolones (U.S. Pat. No. 5,330,992), styryl compounds (U.S. Pat. No. 5,217,999), styryl-substituted pyridyl compounds (U.S. Pat. No.
- the present invention relates to compounds belonging to the 2-(3-amino)arylamino-4-aryl-thiazoles. These compounds are capable of selectively inhibiting signal transduction involving the tyrosine phosphokinase c-kit and mutant forms thereof.
- the invention is aimed at compounds of formula I, which may represent either free base forms of the substances or pharmaceutically acceptable salts thereof: and wherein R 1 is:
- R an d R′ are independently chosen from H or an aryl, heteroaryl, alkyl and cycloalkyl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality;
- R 2 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 3 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 5 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy,
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality;
- R 7 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy.
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2—R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality;
- R 1 has the meaning depicted in c) above
- the invention is directed to compounds of the following formula: wherein R is H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality.
- R is H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality; or a a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and I or bearing a pendant basic nitrogen functionality;
- a —SO2-R group wherein R is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality; or a —CO—R or a —CO—NRR′ group, wherein R and R′ are independently chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality
- the invention is directed to amide-benzylamine compounds of the following formula: wherein R is H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality; a cycloalkyl, aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or an alkyl, cycloalkyl, aryl or heteroaryl group substituted by a alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality;
- a —SO2-R group wherein R is an alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a —CO—R or a —CO—NRR′ group, wherein R and R′ are independently chosen from H or an aryl heteroaryl, alkyl and cycloalkyl group optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality.
- the invention is directed to amide-phenol compounds of the following formula: wherein R is H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality;
- a cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality; or an alkyl, cycloalkyl, aryl or heteroaryl group substituted by a alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality;
- a —SO2-R group wherein R is an alkyl, cycloalkyl, aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality; or a —CO—R or a —CO—NRR′ group, wherein R and R′ are independently chosen from H or an aryl, heteroaryl, alkyl and cycloalkyl group optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality.
- R is H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for example a halogen) and/or bearing a pendant basic nitrogen is functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group substituted by an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- R is H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom (for
- the invention is directed to N-Aminoalkyl-N′-thiazol-2yl-benzene-1,3-diamine compounds of the following formula: wherein Y is a linear or branched alkyl group containing from 1 to 10 carbon atoms;
- Z represents an aryl or heteroaryl group, optionally substituted at one or more ring position with any permutation of the following groups:
- R 2 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 3 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 5 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy.
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl group containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality;
- R 7 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy.
- H an halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- the invention is particularly embodied by the compounds of the following formula II: wherein X is R or NRR′ and wherein R and R′ are independently chosen from H, an aryl, a heteroaryl, an alkyl, or a cycloalkyl group optionally substituted with at least one heteroatom, such as for example a halogen chosen from F, I, Cl and Br and optionally bearing a pendant basic nitrogen functionality, or an aryl, a heteroaryl, an alkyl or a cycloalkyl group substituted with an aryl, a heteroaryl, an alklyl or a cycloalkyl group optionally substituted with at least one heteroatom, such as for example a halogen chosen from F, I, Cl and Br and optionally bearing a pendant basic nitrogen functionality,
- R 2 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 3 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 5 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy.
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- substituent R6 which in the formula II is connected to position 4 of the thiazole ring, may instead occupy position 5 of the thiazole ring.
- the invention is directed to compounds in which X is a substituted alkyl, aryl or heteroaryl group bearing a pendant basic nitrogen functionality represented for example by the structures a to f shown below, wherein the wavy line corresponds to the point of attachment to core structure of formula II:
- X (see formula II) is preferentially group d.
- the invention concerns the compounds in which R 2 and R 3 are hydrogen.
- R 4 is a methyl group and R 5 is H.
- R 6 is preferentially a 3-pyridyl group (cf. structure g below), or a 4-pyridyl group (cf structure h below).
- the wavy line in structure g and h correspond to the point of attachment to the core structure of formula I or II.
- R2, R3, R5 are hydrogen, corresponding to the following formula II-1: wherein X is R or NRR′ and wherein R and R′ are independently chosen from H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality;
- a —SO2-R group wherein R is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a —CO—R or a —CO—NRR′ group, wherein R and R′ are independently chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, allyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy.
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- substituent R6 which in the formula II is connected to position 4 of the thiazole ring, may instead occupy position 5 of the thiazole ring.
- 002 2-(2-methyl-5-amino)phenyl-4-(3-pyridyl)-thiazole
- 003 4-(4-Methyl-piperazin-1-ylmethyl)-N-[3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 004 N-[4-Methyl-3-(4-phenyl-thiazol-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide
- 005 N-[3-([2,4′]Bithiazolyl-2′-ylamino)-4-methyl-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide
- 006 4-(4-Methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyrazin-2-yl-thiazol-2-ylamin
- the invention is particularly embodied by the compounds wherein X is a urea group, a —CO—NRR′ group, corresponding to the [3-(thiazol-2-ylamino)-phenyl]-urea family and the following formula II-2: wherein Ra, Rb are independently chosen from H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I,
- a —SO2-R group wherein R is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a —CO—R or a —CO—NRR′ group, wherein R and R′ are independently chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I, Cl, Br and F, or bearing a pendant basic nitrogen functionality.
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy.
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2—R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- the invention is particularly embodied by the compounds wherein X is a substituted Aryl group, corresponding to the N-[3-(Thiazol-2-ylamino)-phenyl]-amide family and the following formula II-3: wherein Ra, Rb, Rc, Rd, Re are independently chosen from H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl
- a —SO2-R group wherein R is an alkyl, cycloalkyl, aryl or heteroaryl optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a —CO—R or a —CO—NRR′ group, wherein R and R′ are independently chosen from H, an alkyl, a cycloalkyl, an aryl or heteroaryl group optionally substituted with at least one heteroatom, notably selected from I, Cl, Br and F, and or bearing a pendant basic nitrogen functionality;
- Ra, Rb, Rc, Rd, Re may also be any organic radical
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- 028 3-Bromo-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 029 3-Iodo-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 030 4-Hydroxymethyl-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 031 4-Amino-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 032 2-Iodo-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 033 4-Iodo-N-[4-methyl-3-(4
- the invention is particularly embodied by the compounds wherein X is a -substituted-aryl group, corresponding to the 4-(4-substituted-1-ylmethyl)-N-[3-(thiazol-2-ylamino)-phenyl]-benzamide family and the following formula II-4: wherein X is a heteroatom, such as O or N
- Ra, Rb, Rd; Re, Rf, Rg, Rh are independently chosen from H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality;
- Ra, Rb, Rd, Re can also be halogen such as Cl, F, Br, I or trifluoromethyl;
- R 4 is hydrogen, halogen-or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-5 thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- 066 4-(4-methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 067 3,5-Dibromo-4-(4-methyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 068 4-Diethylaminomethyl-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide
- 069 N-[4-Methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-4-morpholin-4- ylmethyl-benzamide
- 070 4-Dipropylaminomothyl-N-[4-methyl-3-(4-pyri
- the invention is particularly embodied by the compounds wherein X is a -aryl-substituted group, corresponding to the 3-Disubstituted-amino-N-[3-(thiazol-2-ylamino)-phenyl]-benzamide family and the following formula II-5: wherein Ra, Rb, Rc, Re, Rf, Rg are independently chosen from H or an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality; a cycloalkyl an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F or bearing a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a
- Ra, Rb, Rc, Re can also be halogen such as Cl, F, Br, I or trifluoromethyl;
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic-heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- H a halogen selected from I, F, Cl or Br
- NH2, NO02 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and/or bearing a pendant basic nitrogen functionality.
- the invention is particularly embodied by the compounds wherein X is a —OR group, corresponding to the family [3-(Thiazol-2-ylamino)-phenyl]-carbamate and the following formula II-6 wherein R is independently chosen from an organic group that can be selected for example from a linear or branched alkyl group containing from 1 to 10 carbon atoms optionally substituted with at least one heteroatom and/or bearing a pendant basic nitrogen functionality; a cycloalkyl, an aryl or heteroaryl group optionally substituted with an heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality; or a cycloalkyl, an aryl or heteroaryl group optionally substituted with a cycloalkyl, an aryl or heteroaryl group optionally substituted with a heteroatom, notably a halogen selected from I, Cl, Br and F and/or bearing a pendant basic nitrogen functionality; or a cycl
- R 4 is hydrogen, halogen or a linear or branched alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl or alkoxy;
- R 6 is one of the following:
- an aryl group such as phenyl or a substituted variant thereof bearing any combination, at any one ring position, of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;
- a heteroaryl group such as a 2, 3, or 4-pyridyl group, which may additionally bear any combination of one or more substituents such as halogen, alkyl groups containing from 1 to 10 carbon atoms, trifluoromethyl and alkoxy;
- a five-membered ring aromatic heterocyclic group such as for example 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, which may additionally bear any combination of one or more substituents such as halogen, an alkyl group containing from 1 to 10 carbon atoms, trifluoromethyl, and alkoxy;s
- H a halogen selected from I, F, Cl or Br
- NH2, NO2 or SO2-R wherein R is a linear or branched alkyl goup containing one or more group such as 1 to 10 carbon atoms, and optionally substituted with at least one heteroatom, notably a halogen selected from I, Cl, Br and F, and o or bearing a pendant basic nitrogen functionality.
- the invention is directed to a process for manufacturing a compound of formula I depicted above. This entails the condensation of a substrate of general formula 10 with a thiourea of the type 11.
- Substituent “L” in formula 10 is a nucleofugal leaving group in nucleophilic substitution reactions (for example, L can be selected from chloro, bromo, iodo, toluenesulfonyloxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, etc., with L being preferentially a bromo group).
- Group R1 in formula 11a corresponds to group R1 as described in formula I.
- Group “PG” in formula 11c is a suitable protecting group of a type commonly utilized by the person skilled in the art.
- Formula 12a is the same as formula I. Therefore, R1 in 12a corresponds to R1 in formula I.
- Formula 12b describes a precursor to compounds of formula I which lack substituent R1.
- R1 the nature of which is as described on page 3 for the general formula I, is achieved by the use of standard reactions that are well known to the person skilled in the art, such as alkylation, acylation, sulfonylation, formation of ureas, etc.
- Formula 12c describes an N-protected variant of compound 12b.
- Group “PG” in formula 12c represents a protecting group of the type commonly utilized by the person skilled in the art. Therefore, in a second phase of the synthesis, group PG is cleaved to transform compound 12c into compound 12b. Compound 12b is subsequently advanced to structures of formula I as detailed above.
- Formula 12d describes a nitro analogue of compound 12b.
- the nitro group of compound 12d is reduced by any of the several methods utilized by the person skilled in the art to produce the corresponding amino group, namely compound 12b.
- Compound 12b thus obtained is subsequently advanced to structures of formula I as detailed above.
- aqueous phase was then basified (pH>12) by addition of 2.5 N aqueous sodium hydroxyde solution.
- the crude product was extracted with ethyl acetate (4 ⁇ 30 mL). The combined organic layers were dried over MgSO 4 and concentrated under reduced pressure to afford a slightly yellow oil which became colorless after purification by Kugelrohr distillation (190° C.) in 68% yield.
- Benzoyl chloride (5.64 g, 80 mmol) was added dropwise to a well-stirred solution of ammonium thiocyanate (3.54 g, 88 mmol) in acetone (50 mL). The mixture was refluxed for 15 min, then, the hydrobromide salt of 2-methyl-5-tert-butoxycarbonylamino-aniline (8.4g, 80 mmol) was added slowly portionswise. After 4 h, the reaction mixture was poured into ice-water (350 mL) and the bright yellow precipitate was isolated by. filtration. This crude solid was then refluxed for 45 min in 70 mL of 2.5 N sodium hydroxide solution. The mixture was cooled down and basified with ammonium hydroxide.
- the invention relates to a pharmaceutical composition
- a pharmaceutical composition comprising a compound as depicted above.
- Such medicament can take the form of a pharmaceutical composition adapted for oral administration, which can be formulated using pharmaceutically acceptable carriers well-known in the art in suitable dosages.
- pharmaceutically acceptable carriers well-known in the art in suitable dosages.
- Such carriers enable the pharmaceutical compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for ingestion by the patient.
- these pharmaceutical compositions may contain suitable pharmaceutically-acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Further details on techniques for formulation and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa.).
- composition of the invention can also take the form of a pharmaceutical or cosmetic composition for topical administration.
- compositions may be presented in the form of a gel, paste, ointment, cream, lotion, liquid suspension aqueous, aqueous-alcoholic or, oily solutions, or dispersions of the lotion or serum type, or anhydrous or lipophilic gels, or emulsions of liquid or semi-solid consistency of the milk type, obtained by dispersing a fatty phase in an aqueous phase or vice versa, or of suspensions or emulsions of soft, semi-solid consistency of the cream or gel type, or alternatively of microemulsions, of microcapsules, of microparticles or of vesicular dispersions to the ionic and/or nonionic type.
- These compositions are prepared according to standard methods.
- composition according to the invention comprises any ingredient commonly used in dermatology and cosmetic. It may comprise at least one ingredient selected from hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, emollients, viscosity enhancing polymers, humectants, surfactants, preservatives, antioxidants, solvents, and fillers, antioxidants, solvents, perfumes, fillers, screening agents, bactericides, odor absorbers and coloring matter.
- oils which can be used in the invention mineral oils (liquid paraffin), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils, synthetic oils, silicone oils (cyclomethicone) and fluorinated oils may be mentioned.
- Fatty alcohols, fatty acids (stearic acid) and waxes (paraffin, carnauba, beeswax) may also be used as fatty substances.
- glycerol stearate As emulsifiers which can be used in the invention, glycerol stearate, polysorbate 60 and the PEG-6/PEG-32/glycol stearate mixture are contemplated.
- hydrophilic gelling agents carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, clays and natural gums may be mentioned, and as lipophilic gelling agents, modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, or alternatively ethylcellulose and polyethylene may be mentioned.
- hydrophilic active agents proteins or protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, vitamins, starch and plant extracts, in particular those of Aloe vera may be used.
- agents As lipophilic active, agents, retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides and essential oils may be used. These agents add extra moisturizing or skin softening features when utilized.
- a surfactant can be included in the composition so as to provide deeper penetration of the compound capable of depleting mast cells, such as a tyrosine kinase inhibitor, preferably a c-kit inhibitor.
- the invention embraces penetration enhancing agents selected for example from the group consisting of mineral oil, water, ethanol, triacetin, glycerin and propylene glycol; cohesion agents selected for example from the group consisting of polyisobutylene, polyvinyl acetate and polyvinyl alcohol, and thickening agents.
- compounds with penetration enhancing properties include sodium lauryl sulfate (Dugard, P. H. and Sheuplein, R. J., “Effects of Ionic Surfactants on the Permeability of Human Epidermis: An Electrometric Study,” J. Invest. Dermatol., V.60, pp. 263-69, 1973), lauryl amine oxide (Johnson et. al., U.S. Pat. No. 4,411,893), azone (Rajadhyaksha, U.S. Pat. Nos. 4,405,616 and 3,989,816) and decylmethyl sulfoxide (Sekura, D. L.
- a second class of chemical enhancers are generally referred to as co-solvents. These materials are absorbed topically relatively easily, and, by a variety of mechanisms, achieve permeation enhancement for some drugs.
- Ethanol (Gale et. al., U.S. Pat. No. 4,615,699 and Campbell et. al., U.S. Pat. Nos. 4,460,372 and 4,379,454)
- dimethyl sulfoxide U.S. Pat. Nos. 3,740,420 and 3,743,727, and U.S. Pat. No. 4,575,515)
- glycerine derivatives U.S. Pat. No. 4,322,433 are a few examples of compounds which have shown an ability to enhance the absorption of various compounds.
- compositions of the invention can also be intended for administration with aerosolized formulation to target areas of a patient's respiratory tract.
- Formulations are preferably solutions, e.g. aqueous. solutions, ethanoic solutions, aqueous/ethanoic solutions, saline solutions, colloidal suspensions and microcrystalline suspensions.
- aerosolized particles comprise the active ingredient mentioned above and a carrier, (e.g., a pharmaceutically active respiratory drug and carrier) which are formed upon forcing the formulation through a nozzle which nozzle is preferably in the form of a flexible porous membrane.
- the particles have a size which is sufficiently small such that when the particles are formed they remain suspended in the air for a sufficient amount of time such that the patient can inhale the particles into the patient's lungs.
- the pharmaceutical preparation is made in that the active substance is dissolved or dispersed in a suitable nontoxic medium and said solution or dispersion atomized to an aerosol, i.e. distributed extremely finely in a carrier gas.
- aerosol i.e. distributed extremely finely in a carrier gas.
- the invention is also directed to aerosol devices comprising the compound as defined above and such a formulation, preferably with metered dose valves.
- compositions of the invention can also be intended for intranasal administration.
- pharmaceutically acceptable carriers for administering the compound to the nasal mucosal surfaces will be readily appreciated by the ordinary artisan. These carriers are described in the Remington's Pharmaceutical Sciences” 16th edition, 1980, Ed. By Arthur Osol, the disclosure of which is incorporated herein by reference.
- the composition can be formulated into a solution, e.g., water or isotonic saline, buffered or unbuffered, or as a suspension, for intranasal administration as drops or as a spray.
- a solution e.g., water or isotonic saline, buffered or unbuffered, or as a suspension
- such solutions or suspensions are isotonic relative to nasal secretions and of about the same pH, ranging e.g., from about pH 4.0 to about pH 7.4 or, from pH 6.0 to pH 7.0.
- Buffers should be physiologically compatible and include, simply by way of example, phosphate buffers.
- a representative nasal decongestant is described as being buffered to a pH of about 6.2 (Remington's, Id. at page 1445).
- a suitable saline content and pH for an innocuous aqueous carrier for nasal and/or upper respiratory administration is described as being buffered to a pH of about 6.2 (Remington's, Id. at page 1445).
- the ordinary artisan can readily determine a suitable saline content and pH for an innocuous aqueous carrier for nasal and/or upper respiratory administration.
- Common intranasal carriers include nasal gels, creams, pastes or ointments with a viscosity of, e.g., from about 10 to about 3000 cps, or from about 2500 to 6500 cps, or greater, may also be used to provide a more sustained contact with the nasal mucosal surfaces.
- Such carrier viscous formulations may be based upon, simply by way of example, alkylcelluloses and/or other biocompatible carriers of high viscosity well known to the art (see e.g., Remington's, cited supra.
- a preferred alkylcellulose is, e.g., methylcellulose in a concentration ranging from about 5 to about 1000 or more mg per 100 ml of carrier.
- a more preferred concentration of methyl cellulose is, simply by way of example, from about 25 to about mg per 100 ml of carrier.
- ingredients such as art known preservatives, colorants, lubricating or viscous mineral or vegetable oils, perfumes, natural or synthetic plant extracts such as aromatic oils, and humectants and viscosity enhancers such as, e.g., glycerol, can also be included to provide additional viscosity, moisture retention and a pleasant texture and odor for the formulation.
- various devices are available in the art for the generation of drops, droplets and sprays.
- a premeasured unit dosage dispenser including a dropper or spray device containing a solution or suspension for delivery as drops or as a spray is prepared containing one or more doses of the drug to be administered and is another object of the invention.
- the invention also includes a kit containing one or more unit dehydrated doses of the compound, together with any required salts and/or buffer agents, preservatives, colorants and the like, ready for preparation of a solution or suspension by the addition of a suitable amount of water.
- Another aspect of the invention is directed to the use of said compound to manufacture a medicament.
- the invention embraces a method for treating a disease related to unregulated c-kit transduction comprising administering an effective amount of a compound as defined above to a mammal in need of such treatment.
- the invention is aimed at a method for treating a disease selected from autoimmune diseases, allergic diseases, bone loss, cancers such as leukemia and GIST, tumor angiogenesis, inflammatory diseases, inflammatory bowel diseases (IED), interstitial cystitis mastocytosis, infections diseases, metabolic disorders, fibrosis, diabetes and CNS disorders comprising administering an effective amount a compound depicted above to a mammal in need of such treatment.
- a disease selected from autoimmune diseases, allergic diseases, bone loss, cancers such as leukemia and GIST, tumor angiogenesis, inflammatory diseases, inflammatory bowel diseases (IED), interstitial cystitis mastocytosis, infections diseases, metabolic disorders, fibrosis, diabetes and CNS disorders
- the above described compounds are useful for manufacturing a medicament for the treatment of diseases related to unregulated c-kit transduction including, but not limited to:
- the invention contemplates the use of the compounds as defined above for treating the different categories which can be classified as follows:
- the category I is composed by two sub-categories (IA and IB).
- Category IA is made by diseases in which mast cell infiltration is strictly localized to the skin. This category represents the most frequent form of the disease and includes : i) urticaria pigmentosa, the most common form of cutaneous mastocytosis, particularly encountered in children, ii) diffuse cutaneous mastocytosis, iii) solitary mastocytoma and iv) some rare subtypes, like bullous, erythrodermic and teleangiectatic mastocytosis. These forms are characterized by their excellent prognosis with spontaneous remissions in children and a very indolent course in adults.
- SM systemic disease
- the category II includes mastocytosis with an associated hematological disorder, such as a myeloproliferative or myelodysplastic syndrome, or acute leukemia These malignant mastocytosis does not usually involve the skin. The progression of the disease depends generally on the type of associated hematological disorder that conditiones the prognosis.
- an associated hematological disorder such as a myeloproliferative or myelodysplastic syndrome, or acute leukemia
- the category III is represented by aggressive systemic mastocytosis in which massive infiltration of multiple organs by abnormal mast cells is common. In patients who pursue this kind of aggressive clinical course, peripheral blood features suggestive of a myeloproliferative disorder are more prominent. The progression of the disease can be very rapid, similar to acute leukemia, or some patients can show a longer survival time.
- mast cell leukemia characterized by the presence of circulating mast cells and mast cell progenitors representing more than 10% of the white blood cells. This entity represents probably the rarest type of leukemia in humans, and has a very poor prognosis, similar to the rapidly progressing variant of malignant mastocytosis. Mast cell leukemia can occur either de novo or as the terminal phase of urticaria pigmentosa or systemic mastocytosis.
- the invention also contemplates the method as depicted for the treatment of recurrent bacterial infections, resurging infections after asymptomatic periods such as bacterial cystitis. More particularly, the invention can be practiced for treating FimH expressing bacteria infections such as Gram-negative enterobacteria including E. coli, Klebsiella pneumoniae, Serratia marcescens, Citrobactor freudii and Salmonella typhimuriun.
- FimH expressing bacteria infections such as Gram-negative enterobacteria including E. coli, Klebsiella pneumoniae, Serratia marcescens, Citrobactor freudii and Salmonella typhimuriun.
- the invention is directed to a method for treating neoplastic diseases such as mastocytosis, canine mastocytoma, human gastrointestinal stromal tumor (“GIST”), small cell lung cancer, non-small cell lung cancer, acute myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, colorectal carcinomas, gastric carcinomas, gastrointestinal stromal tumors, testicular cancers, glioblastomas, and astrocytomas comprising administering a compound as defined herein to a human or mammal, especially dogs and cats, in need of such treatment.
- GIST human gastrointestinal stromal tumor
- the invention is directed to a method for treating allergic diseases such as asthma, allergic rhinitis, allergic sinusitis, anaphylactic syndrome, urticaria, angioedema, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, cutaneous necrotizing venulitis and insect bite skin inflammation and blood sucking parasitic infestation
- allergic diseases such as asthma, allergic rhinitis, allergic sinusitis, anaphylactic syndrome, urticaria, angioedema, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, cutaneous necrotizing venulitis and insect bite skin inflammation and blood sucking parasitic infestation
- administering a compound as defined herein to a human or mammal, especially dogs and cats, in need of such treatment.
- the invention is directed to a method for treating inflammatory diseases such as rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions comprising administering a compound as defined herein to a human in need of such treatment.
- inflammatory diseases such as rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions
- the invention is directed to a method for treating autoimmune diseases such as multiple sclerosis, psoriasis, intestine inflammatory disease, ulcerative colitis, Crohn's disease, rheumatoid arthritis and polyarthritis, local and systemic scleroderma, systemic lupus erythematosus, discoid lupus erythematosus, cutaneous lupus, dermatomyositis, polymyositis, Sjogren's syndrome, nodular panateritis, autoimmune enteropathy, as well as proliferative glomerulonephritis comprising administering a compound as defined herein to a human in need of such treatment.
- autoimmune diseases such as multiple sclerosis, psoriasis, intestine inflammatory disease, ulcerative colitis, Crohn's disease, rheumatoid arthritis and polyarthritis
- local and systemic scleroderma systemic lupus erythe
- the invention is directed to a method for treating graft-versus-host disease or graft rejection in any organ transplantation including kidney, pancreas, liver, heart, lung, and bone marrow comprising administering a compound as defined herein to a human in need of such treatment.
- Table 1 shows the potent inhibitory action of the catalytic activity of c-kit with an IC50 ⁇ 10 ⁇ M. Further experiments (not shown) indicates that at least one compound acts as perfect competitive inhibitors of ATP. TABLE 1 In vitro Inhibition assay results c-kit Compounds IC50 ( ⁇ M) 066; 074; 078; 084; 012; 016; 073; 021; 088; ⁇ 10 ⁇ M 023; 025; 047; 048; 055; 049; 026; 087; 075; 089; 051; 082; 090; 060; 085; 052; 053; 096
- Ba/F3 murine kit and human kit, Ba/F3 mkit ⁇ 27 are derived from the murine L-3 dependent Ba/F3 proB lymphoid cells.
- the FMA3 and P815 cell lines are mastocytoma cells expressing endogenous mutated forms of Kit, i.e., frame deletion in the murine juxtamembrane coding region of the receptor-codons 573 to 579.
- the human leukaemic MC line HMC-1 expresses mutations JM-V560G;
- the membrane was then incubated either with HRP-conjugated goat anti mouse IgG antibody or with HRP-conjugated goat anti rabbit IgG antibody (Immunotech), Proteins of interest were then visualized by incubation with ECL reagent (Amersham).
- Ba/F3 cells were transfected by c-kit gene having ⁇ 27 mutation (GIST model). Ba/F3 expressing the mutated c-kit gene readily proliferate in the absence of IL3 or SCF and are tumorigenic in nude mice.
- Tumor cells (10 6 ) were subcutaneously grafted at Jo
- the tumor size at J14 is about 20 mm 3
- Treated mice received per os twice a day a dose of 100 mg/kg of one compound of formula II-3 during 5 days (from J26 to J30).
- mice were pretreated with the compound of formula II-3 (2 ⁇ , 12.5 mg/kg) for two days (day-2, day-1) before induction of arthritis.
- Arthritis was induced by ip injection of 150-ul serums at days 0 and 2.
- the treatment with the compound (2 ⁇ , 12.5 mg/kg) was continued for 14 days.
- the control mice were injected with, 1% PBS before the induction of arthritis and during the course of the disease.
- Ankle thickness and arthritis score was evaluated for 15 days.
- Table 3A and Table 3B show the number of mice used in this study. Two sets of experiments were done with different number of mice, one with 4 mices the other with 8 mices. TABLE 3 A Treated Mice C57B1/6 2 ⁇ , 12.5 mg/Kg 6
- Treated mice displays significant decrease of tumor size at J30 and J33 compared to control.
- one tested compound of the formula II-3 When administrated per os, one tested compound of the formula II-3displays a significant antitumor activity against tumors cells expressing c-kit ⁇ 27.
- a compound of the formula II-3 has demonstrated significant activity in the in vivo mouse model of arthritis. Results are shown on FIGS. 1, 2 , 3 , 4 .
- FIG. 1 Effect of the compound in serum transfer experiments, Protocol, ip daily treatment with the compound (2 ⁇ 12.5 mg/kg) and on days-2 and -1, set of experiment with 4 mices (T: treated, C: control)
- FIG. 2 Effect of the compound in serum transfer experiments, Protocol , ip daily treatment with the compound (2 ⁇ 12.5 mg/kg) and on days-2 and -1, set of experiment with 4 mices (T: treated, C: control)
- FIG. 3 Effect of the compound in serum transfer experiments, Protocol , ip daily treatment with the compound (2 ⁇ 12.5 mg/kg) and on days-2 and -1, set of experiment with 8 mices (T: treated, C: control)
- FIG. 4 Effect of the compound in serum transfer experiments, Protocol , ip daily treatment with the compound (2 ⁇ 12.5 mg/kg) and on days-2 and -1, set of experiment with 8 mices (T: treated, C: control)
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US13/016,100 US8450302B2 (en) | 2002-08-02 | 2011-01-28 | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US13/015,664 US8835435B2 (en) | 2002-08-02 | 2011-01-28 | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US14/089,946 US8993573B2 (en) | 2002-08-02 | 2013-11-26 | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
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PCT/IB2003/003685 WO2004014903A1 (fr) | 2002-08-02 | 2003-07-31 | 2-(3-aminoaryl)amino-4-aryl-thiazoles et leur utilisation en tant que inhibiteurs de c-kit |
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US11/779,633 Abandoned US20080255141A1 (en) | 2002-08-02 | 2007-07-18 | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US13/015,664 Expired - Lifetime US8835435B2 (en) | 2002-08-02 | 2011-01-28 | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
US14/089,946 Expired - Lifetime US8993573B2 (en) | 2002-08-02 | 2013-11-26 | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US20060292203A1 (en) * | 2005-06-08 | 2006-12-28 | Targegen, Inc. | Methods and compositions for the treatment of ocular disorders |
WO2007052882A1 (fr) * | 2005-11-01 | 2007-05-10 | Amorepacific Corporation | Derives de pyridine thiazole carboxamide, leur procede de preparation, et composition de blanchiment de la peau contenant ces derives |
WO2007056023A2 (fr) * | 2005-11-02 | 2007-05-18 | Targegen, Inc. | Inhibiteurs de thiazoles diriges contre des mutations de kinases resistantes |
US20070259904A1 (en) * | 2005-11-01 | 2007-11-08 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
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US8030487B2 (en) | 2006-07-07 | 2011-10-04 | Targegen, Inc. | 2-amino—5-substituted pyrimidine inhibitors |
US8372971B2 (en) | 2004-08-25 | 2013-02-12 | Targegen, Inc. | Heterocyclic compounds and methods of use |
US8920785B2 (en) | 2010-03-23 | 2014-12-30 | Beiersdorf Ag | Cosmetic or dermatological preparations with a content of one or more thiazole derivates |
US9168245B2 (en) | 2011-07-27 | 2015-10-27 | Ab Science | Selective protein kinase inhibitors |
US10391094B2 (en) | 2010-11-07 | 2019-08-27 | Impact Biomedicines, Inc. | Compositions and methods for treating myelofibrosis |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005507953A (ja) | 2001-03-08 | 2005-03-24 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルベニア | 抗感染剤としての表面的に両親媒性のポリマー |
JP2005500041A (ja) * | 2001-06-29 | 2005-01-06 | アブ サイエンス | 強力で選択的かつ非毒性のc−kit阻害剤 |
DK1401413T3 (da) | 2001-06-29 | 2007-03-26 | Ab Science | Anvendelse af tyrosinkinaseinhibitorer til behandling af allergiske sygdomme |
JP2004537537A (ja) | 2001-06-29 | 2004-12-16 | アブ サイエンス | 炎症性疾患を治療するためのチロシンキナーゼ阻害剤の使用法 |
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US8450302B2 (en) * | 2002-08-02 | 2013-05-28 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
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WO2005111007A1 (fr) | 2004-05-17 | 2005-11-24 | Otsuka Pharmaceutical Co., Ltd. | Composé thiazole et utilisation de celui-ci |
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WO2005115385A1 (fr) * | 2004-05-24 | 2005-12-08 | Ab Science | Utilisation d'inhibiteurs de c-kit pour le traitement de l'acne |
WO2006093813A2 (fr) * | 2005-02-25 | 2006-09-08 | THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA et al. | Polymeres et oligomeres a faces amphiphiles, composition a base de ceux-ci et, leur utilisation dans des procedes de traitement du cancer |
US8088806B2 (en) | 2005-05-09 | 2012-01-03 | Achillion Pharmaceuticals, Inc. | Thiazole compounds and methods of use |
GB0512091D0 (en) * | 2005-06-14 | 2005-07-20 | Novartis Ag | Organic compounds |
US20080207572A1 (en) * | 2005-07-14 | 2008-08-28 | Ab Science | Use of Dual C-Kit/Fgfr3 Inhibitors for Treating Multiple Myeloma |
JP2009506125A (ja) * | 2005-08-29 | 2009-02-12 | ジェラルド・エム・ハウシー | セラミューテイン・モジュレーター |
US20070135368A1 (en) * | 2005-12-09 | 2007-06-14 | Knapp Pamela E | Cell-to-cell transmission of siRNA induced gene silencing in mammalian cells |
WO2007076460A2 (fr) * | 2005-12-23 | 2007-07-05 | Kalypsys, Inc. | Nouveaux thiazole-urees substitues utiles en tant qu'inhibiteurs de proteine-kinases |
DE102005062986A1 (de) | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Propiolsäureamide und ihre Verwendung zur Herstellung von Arzneimitteln |
DE102005062990A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
CA2649755C (fr) * | 2006-04-20 | 2014-12-02 | Janssen Pharmaceutica N.V. | Procede d'inhibition de la kinase de c-kit |
ES2606505T3 (es) | 2007-01-12 | 2017-03-24 | Ab Science | Tratamiento de combinación de cánceres sólidos con antimetabolitos e inhibidores de tirosina quinasa |
US9187485B2 (en) | 2007-02-02 | 2015-11-17 | Baylor College Of Medicine | Methods and compositions for the treatment of cancer and related hyperproliferative disorders |
EP1964848A1 (fr) * | 2007-03-01 | 2008-09-03 | Bayer Schering Pharma Aktiengesellschaft | Procédés de radiofluoration |
BRPI0811939A2 (pt) | 2007-05-22 | 2014-11-25 | Achillion Pharmaceuticals Inc | Tiazóis substituídos por heteroarila |
KR100885692B1 (ko) * | 2007-06-12 | 2009-02-26 | 한국화학연구원 | 2-(3-클로로-4-메톡시)아닐리노-4-아릴싸이아졸 유도체또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및이를 유효성분으로 함유하는 암 예방 및 치료용 약학적조성물 |
MX2010004718A (es) * | 2007-11-01 | 2010-07-28 | Acucela Inc | Compuestos derivados de amina para tratar enfermedades y trastornos oftalmicos. |
US8106209B2 (en) | 2008-06-06 | 2012-01-31 | Achillion Pharmaceuticals, Inc. | Substituted aminothiazole prodrugs of compounds with anti-HCV activity |
CN102421430B (zh) * | 2009-04-06 | 2014-06-25 | 纽若泰克制药株式会社 | 用于预防或治疗烧伤的药物组合物 |
US20120302577A1 (en) * | 2010-01-28 | 2012-11-29 | Ab Science | Treatment of gist with masitinib |
TW201130830A (en) | 2010-02-01 | 2011-09-16 | Ab Science | Combined treatment of pancreatic cancer with gemcitabine and masitinib |
AR080380A1 (es) * | 2010-03-09 | 2012-04-04 | Ab Science | Tratamiento de la demencia tipo alzheimer con masitinib |
TW201204360A (en) | 2010-04-20 | 2012-02-01 | Ab Science | Treatment of multiple sclerosis with MASITINIB |
TW201204719A (en) | 2010-06-02 | 2012-02-01 | Ab Science | Treatment of rheumatoid arthritis with masitinib |
US10045978B2 (en) | 2010-11-05 | 2018-08-14 | Ab Science | Treatment of mastocytosis with masitinib |
US20140147415A1 (en) * | 2010-11-05 | 2014-05-29 | Ab Science | Treatment of mastocytosis with masitinib |
US9078894B2 (en) * | 2011-02-04 | 2015-07-14 | Ab Science | Treatment of severe persistant asthma with masitinib |
EP2680846A4 (fr) * | 2011-03-01 | 2014-08-06 | Npharmakon Llc | Utilisation de n-(4-méthoxyphényl)-1-phényl-1h-pyrazol-3-amine et composés associés |
WO2012136732A1 (fr) | 2011-04-08 | 2012-10-11 | Ab Science | Traitement du myélome multiple au moyen de mastinib |
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WO2014053650A1 (fr) | 2012-10-04 | 2014-04-10 | Ab Science | Utilisation de masitinib pour le traitement du cancer chez des sous-populations de patients identifiées à l'aide de facteurs de prédiction |
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WO2015082496A1 (fr) | 2013-12-02 | 2015-06-11 | Ab Science | Utilisation de masitinib pour le traitement du cancer colorectal |
EP2886543A1 (fr) | 2013-12-18 | 2015-06-24 | Sandoz Ag | Forme cristalline de masitinibe |
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EP3601278B1 (fr) | 2017-03-31 | 2022-10-26 | Sandoz AG | Forme cristalline de masitinibe |
CN108721283A (zh) * | 2017-04-20 | 2018-11-02 | 华东理工大学 | 噻唑衍生物在治疗非淋巴细胞性白血病中的应用 |
EA202192575A1 (ru) | 2019-03-21 | 2022-01-14 | Онксео | Соединения dbait в сочетании с ингибиторами киназ для лечения рака |
US20220401436A1 (en) | 2019-11-08 | 2022-12-22 | INSERM (Institute National de la Santé et de la Recherche Médicale) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
WO2021099616A1 (fr) | 2019-11-22 | 2021-05-27 | Ab Science | Masitinib pour le traitement de la drépanocytose |
EP3831384A1 (fr) | 2019-12-02 | 2021-06-09 | AB Science | Utilisation de masitinib pour le traitement de l'asthme éosinophile |
WO2021148581A1 (fr) | 2020-01-22 | 2021-07-29 | Onxeo | Nouvelle molécule dbait et son utilisation |
KR20220143020A (ko) | 2020-02-20 | 2022-10-24 | 에이비 사이언스 | 다발 경화증 환자 하위집단의 치료를 위한 마시티닙 |
US20230226043A1 (en) | 2020-04-10 | 2023-07-20 | Ab Science | Use of masitinib for the treatment of coronavirus disease 2019 (covid-19) |
CA3201259A1 (fr) | 2020-12-16 | 2022-06-23 | Alain Moussy | Masitinib pour le traitement de la maladie d'alzheimer |
IL308088A (en) | 2021-05-17 | 2023-12-01 | Ab Science | Mestitinib for the treatment of castrate-resistant prostate cancer |
WO2023081923A1 (fr) | 2021-11-08 | 2023-05-11 | Frequency Therapeutics, Inc. | Inhibiteurs du récepteur du facteur de croissance dérivé des plaquettes (pdgfr) alpha et leurs utilisations |
CN114644582B (zh) * | 2022-04-11 | 2024-03-29 | 中原工学院 | 一种苯基双硫脲类化合物的制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3192225A (en) * | 1961-04-24 | 1965-06-29 | Geigy Chem Corp | 2-substituted aminothiazoles |
US3467666A (en) * | 1966-11-07 | 1969-09-16 | Geigy Chem Corp | 2-substituted aminothiazoles |
US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
US20040110810A1 (en) * | 2002-08-02 | 2004-06-10 | Ab Science | 2-(3-Aminoaryl)amino-4-aryl-thiazoles for the treatment of diseases |
Family Cites Families (71)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US590622A (en) * | 1897-09-28 | Edward mcconnell | ||
US3740420A (en) * | 1967-11-28 | 1973-06-19 | Crown Zellerbach Corp | Pharmaceutical compositions with dimethyl sulfoxide |
FR2077803B1 (fr) * | 1970-02-16 | 1973-03-16 | Innothera Lab Sa | |
US3743727A (en) * | 1970-11-16 | 1973-07-03 | Crown Zellerbach Corp | Enhancing tissue penetration of certain antimicrobial agents with dimethyl sulfoxide |
US4405616A (en) * | 1975-06-19 | 1983-09-20 | Nelson Research & Development Company | Penetration enhancers for transdermal drug delivery of systemic agents |
US3989816A (en) * | 1975-06-19 | 1976-11-02 | Nelson Research & Development Company | Vehicle composition containing 1-substituted azacycloheptan-2-ones |
US4343940A (en) * | 1979-02-13 | 1982-08-10 | Mead Johnson & Company | Anti-tumor quinazoline compounds |
CA1163561A (fr) * | 1979-11-06 | 1984-03-13 | Cyril Boroda | Preparation contenant de la nitroglycerine et parfois d'autres medicaments et methode de preparation |
US4379454A (en) * | 1981-02-17 | 1983-04-12 | Alza Corporation | Dosage for coadministering drug and percutaneous absorption enhancer |
US4460372A (en) * | 1981-02-17 | 1984-07-17 | Alza Corporation | Percutaneous absorption enhancer dispenser for use in coadministering drug and percutaneous absorption enhancer |
US4411893A (en) * | 1981-08-14 | 1983-10-25 | Minnesota Mining And Manufacturing Company | Topical medicament preparations |
JPS5968336U (ja) | 1982-10-28 | 1984-05-09 | シャープ株式会社 | 原稿カバ−開閉検出装置 |
CA1236029A (fr) * | 1984-05-14 | 1988-05-03 | Edmund Sandborn | Solutions pharmaceutiques contenant du dimethylsulfoxyde |
US4615699A (en) * | 1985-05-03 | 1986-10-07 | Alza Corporation | Transdermal delivery system for delivering nitroglycerin at high transdermal fluxes |
JPS6328447A (ja) | 1986-07-21 | 1988-02-06 | Toshiba Corp | 加速管 |
JP2752361B2 (ja) | 1986-11-03 | 1998-05-18 | エバレディー、バッテリー、カンパニー、インコーポレーテッド | 正極端子ピンと過塩素酸塩電解質を有する密閉された非水性電池 |
US5217999A (en) * | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
DE3815221C2 (de) * | 1988-05-04 | 1995-06-29 | Gradinger F Hermes Pharma | Verwendung einer Retinol- und/oder Retinsäureester enthaltenden pharmazeutischen Zubereitung zur Inhalation zur Einwirkung auf die Schleimhäute des Tracheo-Bronchialtraktes einschließlich der Lungenalveolen |
GB9413975D0 (en) * | 1994-07-11 | 1994-08-31 | Fujisawa Pharmaceutical Co | New heterobicyclic derivatives |
CA2078214C (fr) | 1990-04-02 | 1995-03-28 | Robert Lee Dow | Inhibiteur de tyrosine kinase a base d'acide phenylmethanephosphonique |
US5302606A (en) * | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
US5714493A (en) * | 1991-05-10 | 1998-02-03 | Rhone-Poulenc Rorer Pharmaceuticals, Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
ES2108120T3 (es) | 1991-05-10 | 1997-12-16 | Rhone Poulenc Rorer Int | Compuestos bis arilicos y heteroarilicos mono- y biciclicos que inhiben tirosina quinasa receptora de egf y/o pdgf. |
US5710158A (en) * | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5721237A (en) * | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
JP2549583B2 (ja) | 1991-05-10 | 1996-10-30 | 明成化学工業株式会社 | セルロース繊維の反応染色における未固着染料の退色防止法 |
US6194439B1 (en) | 1991-05-29 | 2001-02-27 | Pfizer Inc. | Tricyclic polyhydroxylic tyrosine kinase inhibitors |
NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
TW225528B (fr) * | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
HUT71553A (en) | 1992-08-06 | 1995-12-28 | Warner Lambert Co | 2-thioindoles (selenoindoles) and related disulfides (selenides) which inhibit protein tyrosine kinases and which have antitumor properties |
US5330992A (en) * | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
US5656643A (en) * | 1993-11-08 | 1997-08-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US6239172B1 (en) * | 1997-04-10 | 2001-05-29 | Nitrosystems, Inc. | Formulations for treating disease and methods of using same |
JP3728770B2 (ja) | 1995-06-01 | 2005-12-21 | ブラザー工業株式会社 | 原稿読取り装置 |
US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
US5906202A (en) | 1996-11-21 | 1999-05-25 | Aradigm Corporation | Device and method for directing aerosolized mist to a specific area of the respiratory tract |
US5776020A (en) * | 1997-05-19 | 1998-07-07 | Barone; Michael A. | Tensioning device for sporting racquets |
US5883166A (en) * | 1997-06-26 | 1999-03-16 | Jennings; Thomas C. | Liquid internal mold release agents for unsaturated polyester thermosetting molding compounds |
CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
JP4333676B2 (ja) | 1997-11-21 | 2009-09-16 | オムロン株式会社 | プログラム制御装置、プログラム制御方法、およびプログラム記録媒体 |
US6291514B1 (en) * | 1998-02-09 | 2001-09-18 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors |
EP1137415A4 (fr) * | 1998-12-07 | 2002-03-20 | Smithkline Beecham Corp | Inhibiteurs de la myt1 kinase |
JP2002533360A (ja) | 1998-12-31 | 2002-10-08 | スージェン・インコーポレーテッド | 蛋白質キナーゼ活性を調節するためおよび癌の化学療法において用いるための3−ヘテロアリーリデニル−2−インドリノン化合物 |
UA71971C2 (en) * | 1999-06-04 | 2005-01-17 | Agoron Pharmaceuticals Inc | Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases |
ATE414079T1 (de) | 2000-03-01 | 2008-11-15 | Janssen Pharmaceutica Nv | 2,4-disubstituierte thiazolyl derivate |
US7087608B2 (en) | 2000-03-03 | 2006-08-08 | Robert Charles Atkins | Use of PDGF receptor tyrosine kinase inhibitors for the treatment of diabetic nephropathy |
US6586453B2 (en) * | 2000-04-03 | 2003-07-01 | 3-Dimensional Pharmaceuticals, Inc. | Substituted thiazoles and the use thereof as inhibitors of plasminogen activator inhibitor-1 |
US6892245B1 (en) | 2000-09-22 | 2005-05-10 | Nortel Networks Limited | Management information base for a multi-domain network address translator |
JP2002185796A (ja) | 2000-12-11 | 2002-06-28 | Canon Inc | 画像読取処理システムおよび画像読取処理方法、並びに記録媒体 |
ITTO20010110A1 (it) * | 2001-02-08 | 2002-08-08 | Rotta Research Lab | Nuovi derivati benzamidinici dotati di attivita' anti-infiammatoria ed immunosoppressiva. |
GB0108606D0 (en) | 2001-04-05 | 2001-05-23 | Novartis Ag | Organic compounds |
EP1260876B1 (fr) | 2001-05-25 | 2013-05-22 | Ricoh Company, Ltd. | Couvercle pour la plaque d'exposition, dispositif de balayage d'images et dispositif de formation d'images avec le couvercle |
ATE343415T1 (de) | 2001-06-29 | 2006-11-15 | Ab Science | Die verwendung von c-kit hemmer zur behandlung von entzündlichen darmerkrankungen |
WO2003002105A2 (fr) | 2001-06-29 | 2003-01-09 | Ab Science | Utilisation d'inhibiteurs de la tyrosine kinase dans le traitement de la perte osseuse |
JP2004537537A (ja) | 2001-06-29 | 2004-12-16 | アブ サイエンス | 炎症性疾患を治療するためのチロシンキナーゼ阻害剤の使用法 |
EP1471907B1 (fr) | 2001-06-29 | 2008-07-16 | AB Science | Utilisation d'inhibiteurs de c-kit destines a traiter des maladies auto-immunes |
US20050054617A1 (en) | 2001-06-29 | 2005-03-10 | Alain Moussy | Use of potent, selective and non toxic c-kit inhibitors for treating mastocytosis |
JP2005500041A (ja) | 2001-06-29 | 2005-01-06 | アブ サイエンス | 強力で選択的かつ非毒性のc−kit阻害剤 |
DK1401413T3 (da) | 2001-06-29 | 2007-03-26 | Ab Science | Anvendelse af tyrosinkinaseinhibitorer til behandling af allergiske sygdomme |
JP2005502614A (ja) | 2001-06-29 | 2005-01-27 | アブ サイエンス | 多発性硬化症(ms)を治療するためのチロシンキナーゼ阻害剤の使用方法 |
EP1401412A2 (fr) | 2001-06-29 | 2004-03-31 | AB Science | Utilisation d'inhibiteurs de materiel c, puissants, selectifs et non toxiques pour traiter l'angiogenese tumorale |
US20030091974A1 (en) | 2001-06-29 | 2003-05-15 | Alain Moussy | Method for screening compounds capable of depleting mast cells |
WO2003039550A1 (fr) | 2001-09-20 | 2003-05-15 | Ab Science | Utilisation d'inhibiteurs de tyrosine kinase pour blanchir la peau humaine et traiter des troubles associes a un dysfonctionnement des melanocytes |
US20040241226A1 (en) | 2001-09-20 | 2004-12-02 | Alain Moussy | Use of potent, selective and non-toxic c-kit inhibitors for treating bacterial infections |
ATE401078T1 (de) | 2001-09-20 | 2008-08-15 | Ab Science | Die verwendung von c-kithemmern zur förderung des haarwuchses |
JP2003134307A (ja) | 2001-10-26 | 2003-05-09 | Canon Inc | 画像読取装置 |
US20030158199A1 (en) * | 2002-01-25 | 2003-08-21 | Kylix, B.V. | Novel compounds for inhibition of Tie-2 |
CA2474322A1 (fr) | 2002-01-25 | 2003-07-31 | Kylix Pharmaceuticals B.V. | (thia-/oxa-/pyra) zoles substitues 4(hetero-) aryle pour inhibition de tie-2 |
JP5568312B2 (ja) | 2007-02-13 | 2014-08-06 | アーべー・シオンス | キナーゼ阻害剤としての2−アミノチアゾール化合物の合成方法 |
-
2003
- 2003-07-31 CN CNB03823145XA patent/CN100491374C/zh not_active Expired - Lifetime
- 2003-07-31 CA CA2494695A patent/CA2494695C/fr not_active Expired - Lifetime
- 2003-07-31 PT PT03784419T patent/PT1525200E/pt unknown
- 2003-07-31 WO PCT/IB2003/003685 patent/WO2004014903A1/fr active IP Right Grant
- 2003-07-31 IL IL16652803A patent/IL166528A0/xx active IP Right Grant
- 2003-07-31 MX MXPA05001277A patent/MXPA05001277A/es active IP Right Grant
- 2003-07-31 NZ NZ538490A patent/NZ538490A/en not_active IP Right Cessation
- 2003-07-31 JP JP2004527232A patent/JP4726486B2/ja not_active Expired - Lifetime
- 2003-07-31 US US10/523,018 patent/US20050239852A1/en not_active Abandoned
- 2003-07-31 AT AT03784419T patent/ATE375342T1/de active
- 2003-07-31 KR KR1020057001919A patent/KR101036866B1/ko active IP Right Grant
- 2003-07-31 EP EP03784419A patent/EP1525200B1/fr not_active Expired - Lifetime
- 2003-07-31 DE DE60316810T patent/DE60316810T2/de not_active Expired - Lifetime
- 2003-07-31 BR BRPI0313165A patent/BRPI0313165B8/pt not_active IP Right Cessation
- 2003-07-31 ES ES03784419T patent/ES2294344T3/es not_active Expired - Lifetime
- 2003-07-31 DK DK03784419T patent/DK1525200T3/da active
- 2003-08-01 US US10/632,101 patent/US7423055B2/en not_active Expired - Lifetime
-
2005
- 2005-02-15 ZA ZA2005/01331A patent/ZA200501331B/en unknown
- 2005-03-02 NO NO20051115A patent/NO330608B1/no not_active IP Right Cessation
-
2006
- 2006-03-07 HK HK06102936.7A patent/HK1084382A1/xx not_active IP Right Cessation
-
2007
- 2007-07-18 US US11/779,633 patent/US20080255141A1/en not_active Abandoned
- 2007-11-27 CY CY20071101517T patent/CY1107036T1/el unknown
-
2011
- 2011-01-28 US US13/015,664 patent/US8835435B2/en not_active Expired - Lifetime
-
2013
- 2013-11-26 US US14/089,946 patent/US8993573B2/en not_active Expired - Lifetime
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3192225A (en) * | 1961-04-24 | 1965-06-29 | Geigy Chem Corp | 2-substituted aminothiazoles |
US3467666A (en) * | 1966-11-07 | 1969-09-16 | Geigy Chem Corp | 2-substituted aminothiazoles |
US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
US20040110810A1 (en) * | 2002-08-02 | 2004-06-10 | Ab Science | 2-(3-Aminoaryl)amino-4-aryl-thiazoles for the treatment of diseases |
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US20090275569A1 (en) * | 2004-04-08 | 2009-11-05 | Xianchang Gong | Benzotriazine Inhibitors of Kinases |
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US20090275582A1 (en) * | 2005-11-01 | 2009-11-05 | Glenn Noronha | Bi-Aryl Meta-Pyrimidine Inhibitors of Kinases |
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US8030487B2 (en) | 2006-07-07 | 2011-10-04 | Targegen, Inc. | 2-amino—5-substituted pyrimidine inhibitors |
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US7713965B2 (en) | 2008-02-29 | 2010-05-11 | Vetoquinol Sa | 7-substituted 3-carboxy-oxadiazino-quinolone derivatives, their preparation and their application as anti-bacterials |
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