WO2006067445A2 - Csf-1r kinase inhibitors - Google Patents
Csf-1r kinase inhibitors Download PDFInfo
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- WO2006067445A2 WO2006067445A2 PCT/GB2005/004985 GB2005004985W WO2006067445A2 WO 2006067445 A2 WO2006067445 A2 WO 2006067445A2 GB 2005004985 W GB2005004985 W GB 2005004985W WO 2006067445 A2 WO2006067445 A2 WO 2006067445A2
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- 0 CC(*)(CCCCCC1)CCCCC1C(Nc1cc(C(NC2=CN=C*(*)C=C2)=O)c(*)c(*)c1)O Chemical compound CC(*)(CCCCCC1)CCCCC1C(Nc1cc(C(NC2=CN=C*(*)C=C2)=O)c(*)c(*)c1)O 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the invention relates to chemical compounds, or pharmaceutically acceptable salts thereof, which possess colony stimulating factor 1 receptor (CSF-IR) kinase inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body.
- CSF-IR colony stimulating factor 1 receptor
- the invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.
- Receptor tyrosine kinases RTK' s
- RTK's are a sub- family of protein kinases that play a critical role in cell signalling and are involved in a variety of cancer related processes including cell proliferation, survival, angiogenesis, invasion and metastasis. There are believed to be at least 96 different RTK's including CSF-IR.
- CSF-IR or c-fms was originally identified as the oncogene v-fms from the feline sarcoma virus.
- CSF-IR is a member of the class III RTK's along with c-Kit, fms-related tyrosine kinase 3 (Flt3), Platelet-derived growth factor receptor ⁇ and ⁇ (PDGFR ⁇ and PDGFR ⁇ ) All of these kinases have been implicated in the process of tumorigenesis.
- CSF-IR is normally expressed as an immature 130 kDa transmembrane protein and ultimately results in a mature 145-160 kDa cell surface TV-linked glycosylated protein.
- Macrophage colony stimulating factor (M-CSF or CSF-I), the ligand for CSF-IR, binds to the receptor resulting in dimerization, auto-phosphorylation of the receptor and subsequent activation of downstream signal transduction cascades (CJ. Sherr, Biochim Biophys Acta, 1988, 948: 225- 243).
- CSF-IR is normally expressed in myeloid cells of the mononuclear phagocytic lineage and their bone-marrow progenitors as well as the epithelial cells of the ducts and alveoli in the lactating, but not normal resting, breast tissue.
- CSF-IR activation stimulates the proliferation, survival, motility and differentiation of cells of the monocyte/macrophage lineage.
- the mature macrophage plays a key role in normal tissue development and immune defence (F.L. Pixley and E.R. Stanley, Trends in Cell Biology, 2004, 14(11): 628-638).
- osteoblasts secrete CSF-I and activate the receptor on osteoclastic progenitors resulting in differentiation into mature osteoclasts (S.L.
- the CSF-IR axis plays an important role in placental development, embryonic implantation, mammary gland ductal and lobuloalveolar development and lactation (E. Sapi, Exp Biol Med, 2004, 229:1-11).
- CSF-IR Transfection of CSF-IR with or without CSF-I induces transformation and in vivo tumorigenicity of N1H3T3 (Rat2 and ovarian granulosa cells.
- Autocrine and/or paracrine signaling mechanisms have been implicated in the activation of CSF-IR in the tumour epithelium and tumour associated macrophage.
- Aberrant expression and activation of CSF-IR and/or its ligand have been found in human myeloid leukaemia, prostate, breast, ovarian, endometrial and a variety of other cancers.
- a number of studies have demonstrated that the overexpression of CSF-IR is associated with poor prognosis in several of these cancers.
- CSF-I /CSF- IR axis plays a key role in the regulation of tumour-associated macrophage, which have been postulated to play a significant role in tumour angiogenesis, invasion and progression (E. Sapi, Exp Biol Med, 2004, 229:1-11).
- AstraZeneca application WO 00/55120 discloses certain amide derivatives which are inhibitors of the production of cytokines such as TNF, in particular of TNF ⁇ , and various interleukins, in particular IL-I .
- the present inventors have surprisingly found that certain other, novel, amide derivatives are potent CSF-IR kinase inhibitors and are accordingly expected to be useful in the treatment of neoplastic disease.
- Ring A is carbocyclyl or heterocyclyl; wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 5 ;
- R 1 is a substituent on carbon and is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci -6 alkoxy, Ci -6 alkanoyl, C
- R 2 is selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci -6 alkoxy, Ci -6 alkanoyl, Ci -6 alkanoyloxy, N-(Ci -6 alkyl)amino, N,N-(C i -6 alkyl) 2 amino, Ci- 6 alkanoylamino, TV, TV-(C i -6 alkyl) 2 carbamoyl, Ci -6 alkylS(O) a wherein a is 0 to 2, C 1-6 alkoxycarbonyl, TV-(Ci -6 alkyl)sulphamoyl,
- R is selected from halo, hydroxy, cyano, methyl, methoxy or hydroxymethyl
- R is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, ureido, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C
- R 4 may be optionally substituted on carbon by one or more R 16 ; and wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 17 ; m is selected from 0-4; wherein the values of R 4 may be the same or different;
- R 8 and R 12 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C
- R 16 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C ⁇ -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl,
- R 6 , R 7 , R 10 , R", R 14 , R 15 , R 18 , R 19 , R 22 and R 23 are independently selected from a direct bond, -O-, -N(R 26 )-, -C(O)-, -N(R 27 )C(O)-, -C(O)N(R 28 )-, -S(O) 8 -, -SO 2 N(R 29 )- or -N(R 30 )SO 2 -; wherein R 26 , R 27 , R 28 , R 29 and R 30 are independently selected from hydrogen or
- Ci -6 alkyl and s is 0-2;
- R 5 , R 9 , R 13 , R 17 , R 21 and R 25 are independently selected from Ci -6 alkyl, Ci -6 alkanoyl,
- Ci -6 alkylsulphonyl Ci -6 alkoxycarbonyl, carbamoyl, N-(C
- R 20 and R 24 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, /V-methyl-/V-ethylamino, acetylamino, /V-methylcarbamoyl, /V-ethylcarbamoyl,
- Ring A is carbocyclyl or heterocyclyl; wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 5 ;
- R 1 is a substituent on carbon and is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, C
- Ci -6 alkynyl C] -6 alkoxy, Ci -6 alkanoyl, Ci -6 alkanoyloxy, N-(Ci -6 alkyl)amino, iV, ⁇ / -(Ci -6 alkyl) 2 amino, C
- R 2 is selected from hydrogen, halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci -6 alkoxy,
- Ci-6alkanoyl Ci -6 alkanoyloxy, TV-(C i -6 alkyl)amino, TV, TV-(C i. 6 alkyl) 2 amino,
- R 4 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci ⁇ alkoxy,
- Ci-6alkanoyl C ⁇ -6 alkanoyloxy, N-(Ci -6 alkyl)amino, N,N-(Ci-6alkyl) 2 amino, C ⁇ - 6 alkanoylamino, N-(C
- R 6 , R 7 , R 10 , R 11 , R 14 , R 15 , R 18 , R 19 , R 22 and R 23 are independently selected from a direct bond, -O-, -N(R 26 )-, -C(O)-, -N(R 27 )C(O)-, -C(O)N(R 28 )-, -S(O) 5 -, -SO 2 N(R 29 )- or
- R 26 , R 27 , R 28 , R 29 and R 30 are independently selected from hydrogen or
- Ci -6 alkyl and s is 0-2; R 5 , R 9 , R 13 , R t7 , R 2 ' and R 25 are independently selected from C )-6 alkyl, C
- R 20 and R 2 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, 7V-methyl-N-ethylamino, acetylamino, iV-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, ⁇ vV-diethylcarbamoyl, TV-methyl-iV-ethyl
- alkyl includes both straight and branched chain alkyl groups. References to individual alkyl groups such as “propyl” are specific for the straight chain version only and references to individual branched chain alkyl groups such as 'isopropyl' are specific for the branched chain version only.
- “Ci -6 alkyl” includes Cualkyl, Ci -3 alkyl, propyl, isopropyl and /-butyl.
- phenylCi -6 alkyl includes phenylCualkyl, benzyl, 1 -phenylethyl and 2-phenylethyl.
- halo refers to fluoro, chloro, bromo and iodo.
- a “heterocyclyl” is a saturated, partially saturated or unsaturated, mono or bicyclic ring containing 4-12 atoms of which at least one atom is chosen from nitrogen, sulphur or oxygen, which may, unless otherwise specified, be carbon or nitrogen linked, whereiti a -CH 2 - group can optionally be replaced by a -C(O)- and a ring sulphur atom may be optionally oxidised to form the S-oxides.
- heterocyclyl examples and suitable values of the term "heterocyclyl” are morpholino, piperidyl, pyridyl, pyranyl, pyrrolyl, pyrazolyl, isothiazolyl, indolyl, quinolyl, thienyl, 1,3-benzodioxolyl, thiadiazolyl, piperazinyl, thiazolidinyl, pyrrolidinyl, thiomo ⁇ holino, pyrrolinyl, homopiperazinyl, 3,5-dioxapiperidinyl, tetrahydropyranyl, imidazolyl, pyrimidyl, pyrazinyl, pyridazinyl, isoxazolyl, W-methylpyrrolyl, 4-pyridone, 1-isoquinolone, 2-pyrrolidone, 4-thiazolidone, pyridine-N-oxide and quinoline-W-oxide.
- heterocyclyl is pyrazolyl.
- a “heterocyclyl” is a saturated, partially saturated or unsaturated, monocyclic ring containing 5 or 6 atoms of which at least one atom is chosen from nitrogen, sulphur or oxygen, it may, unless otherwise specified, be carbon or nitrogen linked, a -CH 2 - group can optionally be replaced by a -C(O)-and a ring sulphur atom may be optionally oxidised to form the S-oxides.
- a “carbocyclyl” is a saturated, partially saturated or unsaturated, mono or bicyclic carbon ring that contains 3-12 atoms; wherein a -CH 2 - group can optionally be replaced by a -C(O)-. Particularly “carbocyclyl” is a monocyclic ring containing 5 or 6 atoms or a bicyclic ring containing 9 or 10 atoms.
- Suitable values for "carbocyclyl” include cyclopropyl, cyclobutyl, 1 -oxocyclopentyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, naphthyl, tetralinyl, indanyl or 1-oxoindanyl.
- a particular example of “carbocyclyl” is phenyl.
- -6 alkanoyloxy” is acetoxy.
- Examples of "Ci -6 alkoxycarbonyl” include methoxycarbonyl, ethoxycarbonyl, n- and t-butoxycarbonyl.
- Examples of "Ci -6 alkoxy” include methoxy, ethoxy and propoxy.
- Examples of “Ci -6 alkanoylamino” include formamido, acetamido and propionylamino.
- Examples of "Ci -6 alkylS(O) a wherein a is 0 to 2” include methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, mesyl and ethylsulphonyl. Examples include propionyl and acetyl.
- -6 alkyl)amino include methylamino and ethylamino.
- -6 alkyl) 2 amino” include di-N-methylamino, di-(W-ethyl)amino and N-ethyl-W-methylamino.
- Examples of "C 2-6 alkenyl” are vinyl, allyl and 1-propenyl.
- Examples of "C 2-6 alkynyl” are ethynyl, 1-propynyl and 2-propynyl.
- Examples of 'W-(Ci -6 alkyl)sulphamoyl are W-(methyl)sulphamoyl and W-(ethyl)sulphamoyl.
- -6 alkyl) 2 sulphamoyl" are 7V,W-(dimethyl)sulphamoyl and jV-(methyl)-N-(ethyl)sulphamoyl.
- Examples of 'W-(Ci - 6 alkyl)carbamoyl are
- 'W,/V-(C ⁇ -6 alkyl) 2 carbamoyl are W,7V-(Cualkyl) 2 carbamoyl, dimethylaminocarbonyl and methylethylaminocarbonyl.
- . 6 alkylsulphonyl” are mesyl, ethylsulphonyl and isopropylsulphonyl.
- Examples of "Ci- ⁇ alkylsulphonylamino” are mesylamino, ethyl sulphonylamino and isopropylsulphonylamino. are methoxycarbonylamino and /-butoxycarbonylamino.
- -6 alkyl)-N-(Ci -6 alkoxy)sulphamoyl are N-(methyl)-N-(methoxy)sulphamoyl and N-(ethyl)-N-(propoxy)sulphamoyl.
- Example of "N,N'-(Ci- 6 alkyl) 2 ureido” are N,jV'-dimethylureido and N-methyl-N'-propylureido.
- Examples of "N'N'-(Ci -6 alkyl) 2 ureido” are N' N'-diethylureido and jV'-methyl-N'-propylureido.
- N-(C ⁇ -6 alkyl)-N',N'-(Ci -6 alkyl) 2 ureido are N-(methyl)-N'-ethyl-N'-isopropylureido and N-ethyl-N',N -diethylureido.
- Examples of 'W-(C i -6 alky I)-N-(C i -6 alkoxy)amino are N-(methyl)-N-(propoxy)amino and N-methyl-N-methoxyamino.
- a suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid-addition salt of a compound of the invention which is sufficiently basic, for example, an acid-addition salt with, for example, an inorganic or organic acid, for example hydrochloric, hydrobromic, sulphuric, phosphoric, trifluoroacetic, citric or maleic acid.
- a suitable pharmaceutically acceptable salt of a compound of the invention which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, an ammonium salt or a salt with an organic base which affords a physiologically-acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.
- an alkali metal salt for example a sodium or potassium salt
- an alkaline earth metal salt for example a calcium or magnesium salt
- an ammonium salt or a salt with an organic base which affords a physiologically-acceptable cation
- a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxye
- Some compounds of the formula (I) may have chiral centres and/or geometric isomeric centres (E- and Z- isomers), and it is to be understood that the invention encompasses all such optical, diastereoisomers and geometric isomers that possess CSF-IR kinase inhibitory activity.
- the invention further relates to any and all tautomeric forms of the compounds of the formula (I) that possess CSF-IR kinase inhibitory activity.
- Ring A is carbocyclyl
- Ring A is phenyl
- Ring A is heterocyclyl; wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 5 .
- Ring A is pyridyl.
- Ring A is pyrazolyl; wherein said pyrazolyl may be optionally substituted on nitrogen by a group selected from R 5 .
- Ring A is thienyl
- Ring A is imidazo[l,2-a]pyridinyl. Ring A is indolyl.
- Ring A is 2,3-dihydrobenzofuranyl.
- Ring A is isoxazolyl.
- Ring A is benzimidazolyl.
- Ring A is 2-oxoindolinyl. Ring A is furanyl.
- Ring A is 1,3-thiazolyl.
- Ring A is pyrimidinyl
- Ring A is pyrrolyl
- Ring A is cyclopropyl. Ring A is tetrahydrofuranyl.
- Ring A is cyclohexyl
- Ring A is cycloheptyl
- Ring A is pyrrolidinyl
- Ring A is phenyl, pyridyl, pyrazolyl, thienyl, indolyl, 2,3-dihydrobenzofuranyl, imidazofl,2-a]pyridinyl, isoxazolyl, benzimidazolyl, 2-oxoindolinyl, furanyl, 1,3-thiazolyl, pyrimidinyl, pyrrolyl, cyclopropyl, tetrahydrofuranyl, cyclohexyl, cycloheptyl and pyrrolidinyl; wherein said pyrazolyl, indolyl, pyrrolyl or pyrrolidinyl may be optionally substituted on nitrogen by a group selected from R 5 ; wherein
- R 5 is selected from C ⁇ -6 alkyl, Ct- ⁇ alkanoyl or Ci -6 alkoxycarbonyl.
- Ring A is phenyl, pyridyl, pyrazolyl, thienyl, indolyl, 2,3-dihydrobenzofuranyl and imidazo[l,2-a]pyridinyl; wherein said pyrazolyl may be optionally substituted on nitrogen by a group selected from R 5 ; wherein
- R 5 is Ci -6 alkyl.
- Ring A is phenyl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, l-methylpyrazol-5-yl, 1-/- butylpyrazol-5-yl, thien-2-yl, thien-3-yl, indol-2-yl, 1 -methylindol-2-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, 2,3-dihydrobenzofuran-7-yl, imidazofl,2-a]pyridin-2-yl, isoxazol-3-yl, pyrrol-2-yl, benzimidazol-6-yl, 1 -methyl-2-oxoindolin-5-yl, furan-2-yl, l,3-thiazol-5-yl, pyrimidin-4-yl
- Ring A is phenyl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, l-methylpyrazol-5-yl, thien-2-yl, thien-3-yl, indol-5-yl, indol-6-yl, 2,3-dihydrobenzofuran-7-yl or imidazo[l,2-a]pyridinyl. Ring A is not pyridyl.
- Ring A is not pyrid-4-yl.
- R 1 is a substituent on carbon and is selected from halo, cyano, hydroxy, sulphamoyl, Ci- ⁇ alkyl, C 2-6 alkynyl, Ci- ⁇ alkoxy, N,N-(Ci -6 alkyl) 2 amino, Ci -6 alkylS(O) a wherein a is 0 to 2, C ⁇ - 6 alkoxycarbonylamino, N-(Ci -6 alkyl)sulphamoyl, NN-(Ci -6 alkyl) 2 Sulphamoyl, TV-(C i -6 alky I)-N-(C i- 6 alkoxy)sulphamoyl, N'N'-(Ci -6 alkyl) 2 ureido, Ci -6 alkylsulphonylamino, carbocyclyl-R 6 - or heterocyclyl-R 7 -; wherein R 1 may be optionally substituted on carbon by one or more R ;
- R 8 is selected from halo, cyano, hydroxy, Ct -6 alkyl, Ci -6 alkoxy, NN-(Ci -6 alkyl) 2 amino, NN-(Ci -6 alkyl) 2 carbamoyl, Ci- 6 alkylS(O) a wherein a is 0 to 2, NN-(Ci -6 alkyl) 2 sulphamoyl, N-(C i -6 alky I)-N-(C i -6 alkoxy)amino, carbocyclyl-R 18 - or heterocyclyl-R 9 -; wherein R 8 may be optionally substituted on carbon by one or more R 20 ; and wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 21 ;
- R 6 , R 7 , R 18 and R 19 are independently selected from a direct bond, -O-, -S(O) 5 - or -N(R 30 )SO 2 -; wherein R 30 is selected from hydrogen and s is 2;
- R 21 is selected from Cj -6 alkyl
- R 20 is selected from cyano or hydroxy.
- R is a substituent on carbon and is selected from halo, cyano, Ci -6 alkyl, C 2-6 alkynyl, C ⁇ -6 alkoxy, NN-(C] -6 alkyl) 2 amino, Ci-6alkylS(O) a wherein a is 0 to 2, NN-(Ci -6 alkyl) 2 sulphamoyl, C] -6 alkylsulphonylamino, carbocyclyl-R 6 - or heterocyclyl-R 7 -; wherein R may be optionally substituted on carbon by one or more R ; R 8 is selected from halo, cyano, hydroxy, ⁇ / ,N-(Ci. 6 alkyl) 2 amino or heterocyclyl-R 9 -; wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 2 ;
- R 6 , R 7 and R 19 are independently selected from a direct bond, -S(O) 5 - or -N(R 30 )SO 2 -; wherein R 30 is hydrogen and s is 0-2;
- R 21 is Ci- ⁇ alkyl.
- R is a substituent on carbon and is selected from fluoro, chloro, bromo, iodo, cyano, hydroxy, sulphamoyl, methyl, ethyl, isopropyl, sec-butyl, t-butyl, 2-methylbut-2-yl, 3- methylbut-2-yl, l,l-dimethylprop-2-yn-l-yl, l,l-dimethylbut-2-yn-l-yl, 3,3-dimethylbut-l- yn- 1 -yl, 3-methylbut- 1 -yn- 1 -yl, methoxy, ethoxy, propoxy, isopropoxy, isobutoxy, 7V,N-dimethylamino, jV,7V-diethylamino, methylthio, mesyl, t-butoxycarbonylamino, 7V-methylsulphamoyl, jV-methyl-TV-propyl
- R 8 is selected from fluoro, cyano, hydroxy, methyl, methoxy, ⁇ jV-dimethylamino, •tyiV-dimethylcarbamoyl, methylthio, mesyl, 7V,iV-dimethylsulphamoyl, N-(methyl)-jV-(methoxy)sulphamoyl, cyclopropyl-R 18 -, piperazinyl-R 19 -, pyrrolyl-R 19 - or tetrahydrofuryl-R 19 -; wherein R 8 may be optionally substituted on carbon by one or more R 20 ; and wherein said piperazinyl may be optionally substituted on nitrogen by a group selected from R 21 ;
- R 6 , R 7 , R 18 and R 19 are independently selected from a direct bond, -O-, -S(O) 5 - or -N(R 30 )SO 2 -; wherein R 30 is selected from hydrogen and s is 2;
- R 21 is selected from methyl or ethyl
- R 20 is selected from cyano or hydroxy.
- R is a substituent on carbon and is selected from fluoro, chloro, bromo, iodo, cyano, methyl, isopropyl, t-butyl, 3-methylbut- 1-yn-l-yl, 3,3-dimethylbut-l-yn-l-yl, methoxy, propoxy, isopropoxy, isobutoxy, dimethylamino, methylthio, mesyl, jV,yV-dimethylsulphamoyl, mesylamino, cyclopropyl-R 6 - or azetidin-1-yl-R 7 -; wherein R may be optionally substituted on carbon by one or more R 8 ;
- R 8 is selected from fluoro, cyano, hydroxy, dimethylamino or piperazin-1-yl-R 9 -; wherein said piperazinyl may be optionally substituted on nitrogen by a group selected from R 21 ;
- R 6 , R 7 and R 19 are independently selected from a direct bond, -S(O) 5 - or -N(R 30 )SO 2 -; wherein R 30 is hydrogen and s is 2;
- R 21 is methyl or ethyl.
- R 1 is a substituent on carbon and is selected from fluoro, chloro, bromo, iodo, cyano, hydroxy, sulphamoyl, methyl, trifluoromethyl, 1 -cyano- 1 -methylethyl, methoxy, ethoxy, propoxy, isopropoxy, isobutoxy, /V,/V-dimethylamino, difluoromethylthio, yV./V-dimethylsulphamoyl, /-butyl, mesyl, cyclopropylaminosulphonyl, azetidin-1-ylsulphonyl, tetrahydrofuran-2-ylmethylaminosulphonyl, N-methyl-N-(2,3-dihydroxypropyl)sulphamoyl, mesylamino, morpholinosulphonyl, l-methylpiperazin-4-ylmethyl, 1 -ethylpiperaz
- R 1 is a substituent on carbon and is selected from fluoro, chloro, bromo, iodo, cyano, methyl, t-butyl, trifluoromethyl, dimethylaminomethyl, 1 -methyl- 1-cyanoethyl, A- methylpiperazin-1 -ylmethyl, 4-ethylpiperazin-l -ylmethyl, 3-hydroxy-3-methylbut-l-yn-l-yl, 3,3-dimethylbut-l-yn-l-yl, methoxy, propoxy, isopropoxy, isobutoxy, dimethylamino, difluoromethylthio, /V,/V-dimethylsulphamoyl, mesyl, cyclopropylaminosulphonyl, azetidin-1- ylsulphonyl or mesylamino.
- R 1 is a substituent on carbon and is selected from 1 -methyl- 1-cyanoethyl.
- R 1 is a substituent on carbon and is selected from trifluoromethyl. n is selected from 0-2; wherein the values of R 1 may be the same or different. n is 0. n is 1. n is 2; wherein the values of R may be the same or different. R 2 is hydrogen.
- R 3 is selected from halo, methyl or methoxy.
- R 3 is selected from halo or methyl.
- R 3 is selected from fluoro, chloro, methyl or methoxy.
- R 3 is selected from fluoro, chloro or methyl.
- R 3 is fluoro
- R 3 is chloro
- R 3 is methyl
- R 3 is methoxy. R 3 is not chloro.
- R 4 is selected from halo, cyano, hydroxy, amino, carbamoyl, ureido, Ci -6 alkyl, C 2-6 alkynyl, Ci- ⁇ alkoxy, TV-(C i -6 alkyl)amino, TV, TV-(C i -6 alkyl) 2 amino, C] -6 alkanoylamino, TV-(C ⁇ -6 alkyl)carbamoyl, Ci- ⁇ alkoxycarbonyl, TV, TV-(C i- 6 alkyl) 2 sulphamoyl, Ci -6 alkylsulphonylamino, carbocyclyl-R 1 - or heterocyclyl-R 5 -; wherein R may be optionally substituted on carbon by one or more R 6 ; and wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 7 ;
- R 6 is selected from halo, hydroxy, amino, Ci -6 alkoxy, TV-(C ]. 6 alkyl)amino, TV, TV-(C i -6 alkyl) 2 amino, carbocyclyl-R 22 - or heterocyclyl-R 23 -; wherein R 16 may be optionally substituted on carbon by one or more R 24 ; and wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 25 ;
- R 14 , R 15 , R 22 and R 23 are independently selected from a direct bond, -N(R 26 )- or -C(O)N(R 28 )-; wherein R 26 and R 28 are hydrogen;
- R 7 and R 25 are independently selected from and Ci -6 alkoxycarbonyl
- R 24 is methyl or phenyl.
- R 4 is selected from halo, cyano, amino, C
- R 15 is a direct bond.
- R is selected from fluoro, chloro, bromo, cyano, hydroxy, amino, carbamoyl, ureido, methyl, ethyl, propyl, prop-1-ynyl, methoxy, ethoxy, propoxy, isopropoxy, acetyl, methylamino, ethylamino, propylamino, isopropylamino, butylamino, dimethylamino, TV- methyl-TV-ethylamino, TV-methyl-7V-propylamino, formylamino, acetylamino, propanoylamino, 2,2-dimethylpropanoylamino, TV-methylcarbamoyl, methoxycarbonyl, TV.TV-dimethylsulphamoyl, mesylamino, cyclopropyl-R -, cyclobutyl-R -, piperazinyl-R 5 -, pyr
- R 16 is selected from fluoro, hydroxy, amino, methoxy, methylamino, ⁇ jV-dimethylamino, cyclopropyl-R 22 -, 1,3-dioxolanyl-R 23 -, imidazolyl-R 23 -, morpholino-R 23 -, piperazinyl-R 23 -, piperidinyl-R 23 - or pyrrolidinyl-R 23 -; wherein R 16 may be optionally substituted on carbon by one or more R 24 ; and wherein said piperazinyl or pyrrolidinyl may be optionally substituted on nitrogen by a group selected from R 25 ;
- R 14 , R 15 , R 22 and R 23 are independently selected from a direct bond, -N(R 26 )- or -C(O)N(R 28 )-; wherein R 26 and R 28 are hydrogen;
- R 17 and R 25 are independently selected from methyl and /-butoxycarbonyl; R 24 is methyl or phenyl.
- R 4 is selected from fluoro, chloro, bromo, cyano, amino, methyl, methoxy, methylamino, acetylamino, 7V-methylcarbamoyl or morpholino.
- R 4 is selected from fluoro, chloro, bromo, cyano, hydroxy, amino, carbamoyl, ureido, methyl, ethyl, methoxy, methylamino, isopropylamino, morpholino, 2- (dimethylamino)ethylamino, 2-(hydroxy)ethylamino, 2-(amino)ethylamino, 3-(pyrrolidin-l- yl)propylamino, 7V-methylcarbamoyl, acetylamino, 2-hydroxyacetylamino, trifluoromethyl, mesylamino, 2,2-dimethylpropanoylamino, 3-methoxypropanoylamino
- Ring A is carbocyclyl or heterocyclyl; wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 5 ;
- R 1 is a substituent on carbon and is selected from halo, cyano, hydroxy, sulphamoyl, Ci -6 alkyl, C 2-6 alkynyl, N,N-(C
- R 2 is hydrogen
- R 3 is selected from halo, methyl or methoxy;
- R 4 is selected from halo, cyano, hydroxy, amino, carbamoyl, ureido,
- R 5 is selected from Cualkyl, Ci- ⁇ alkanoyl or C] -6 alkoxycarbonyl; m is selected from 0-2; wherein the values of R 4 may be the same or different;
- R 6 , R 7 , R 18 and R 19 are independently selected from a direct bond, -O-, -S(O) 5 - or -N(R 30 )SO 2 -; wherein R 30 is selected from hydrogen and s is 2; R is selected from halo, cyano, hydroxy, Ci -6 alkyl, C
- R 14 , R 15 , R 22 and R 23 are independently selected from a direct bond, -N(R 26 )- or
- R 26 and R 28 are hydrogen;
- R 16 is selected from halo, hydroxy, amino, 7V-(Ci -6 alkyl)amino,
- R 17 and R 25 are independently selected from Ci -6 alkyl and C
- R 20 is selected from cyano or hydroxy;
- R 24 is methyl or phenyl; or a pharmaceutically acceptable salt thereof; with the proviso that said compound is not: N- [4-chloro-3 -( ⁇ [6-(4-methy lpiperazin- 1 -y l)pyridin-3 -y l]amino ⁇ carbony l)phenyl]-2- morpholin-4-ylisonicotinamide; jV-[4-chloro-3-( ⁇ t6-(4-ethylpiperazin-l-yl)pyridin-3-yl]amino ⁇ carbonyl)phenyl]-2-morpholin-
- Ring A is phenyl, pyridyl, pyrazolyl, thienyl, indolyl, 2,3-dihydrobenzofuranyl and imidazo[l ,2-a]pyridinyl; wherein said pyrazolyl may be optionally substituted on nitrogen by a group selected from R 5 ; R 1 is a substituent on carbon and is selected from halo, cyaho, C]. 6 alkyl, C 2-6 alkynyl,
- R 2 is hydrogen
- R 3 is selected from halo or methyl
- R 4 is selected from halo, cyano, amino, Ci -6 alkyl, Ci -6 alkoxy, N-(Ci -6 alkyl)amino, Ci -6 alkanoylamino, N-(Ci -6 alkyl)carbamoyl or heterocyclyl-R 15 -; m is selected from 0-2; wherein the values of R 4 may be the same or different;
- R 5 is Ci -6 alkyl
- R 6 , R 7 and R 19 are independently selected from a direct bond, -S(O) 5 - or -N(R 30 )SO 2 -; wherein R 30 is hydrogen and s is 0-2; R 8 is selected from halo, cyano, hydroxy, iY,N-(Ci. 6 alkyl) 2 amino or heterocyclyl-R 19 -; wherein if said heterocyclyl contains an -NH- moiety that nitrogen may be optionally substituted by a group selected from R 2 ;
- R 15 is a direct bond
- R 21 is Cualkyl; or a pharmaceutically acceptable salt thereof; with the proviso that said compound is not:
- Ring A is phenyl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 1 -methy lpyrazol-5-yl, l-t- butylpyrazol-5-yl, thien-2-yl, thien-3-yl, indol-2-yl, 1 -methy lindol-2-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, 2,3-dihydrobenzofuran-7-yl, imidazo[l ,2-a]pyridin-2-yl, isoxazol-3-yl, pyrrol-2-yl, benzimidazol-6-yl, l-methyl-2-oxoindolin-5-yl, furan-2-yl, l,3-thiazol-5-yl, pyrimidin-4-yl, 1
- N N-dimethylcarbamoyl- 1 -methylethyl, 4-methylimidazol- 1 -yl, 1 -(cyclopropyl)- 1 - methylethyl, 2-methyl-3,4-dihydroxybut-2-yl, 2-methylbut-2-yl, 1 -hydroxy-l- cyclopropylethyl, 1-cyanoethyl, 2-cyano-3-methylbut-2-yl, 2-cyanobut-2-yl, l-hydroxy-2- cyanoprop-2-yl and 2-cyanopyrrol-l-ylmethyl; n is selected from 0-2; wherein the values of R 1 may be the same or different;
- R 2 is hydrogen
- R 3 is selected from fluoro, chloro, methyl or methoxy
- R is selected from fluoro, chloro, bromo, cyano, hydroxy, amino, carbamoyl, ureido, methyl, ethyl, methoxy, methylamino, isopropylamino, morpholino, 2- (dimethylamino)ethylamino, 2-(hydroxy)ethylamino, 2-(amino)ethylamino, 3-(pyrrolidin-l- yl)propylamino, 7V-methylcarbamoyl, acetylamino, 2-hydroxyacetylamino, trifluoromethyl, mesylamino, 2,2-dimethylpropanoylamino, 3-methoxypropanoylamino, cyclobutylcarbonylamino, cyclopropyl amino, 2,3-dihydroxypropylamino, 1 ,3-dihydroxyprop- 2-ylamino, 1 -methylpiperazin-4-yl,
- Ring A is phenyl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 1 -methylpyrazol-5-yl, thien-2-yl, thien-3-yl, indol-5-yl, indol-6-yl, 2,3-dihydrobenzofuran-7-yl or imidazo[l,2-a]pyridinyl;
- R is a substituent on carbon and is selected from fluoro, chloro, bromo, iodo, cyano, methyl, t-butyl, trifluoromethyl, dimethylaminomethyl, 1 -methyl- 1-cyanoethyl, 4- methylpiperazin-1-ylmethyl, 4-ethylpiperazin-l-ylmethyl, 3-hydroxy-3-methylbut-l-yn-l-yl, 3,3-dimethylbut-l-yn-l-yl, methoxy, propoxy, isopropoxy, isobutoxy, dimethylamino, difluoromethylthio, TV.jV-dimethylsulphamoyl, mesyl, cyclopropylaminosulphonyl, azetidin-1- ylsulphonyl or mesylamino; n is selected from 0-2; wherein the values of R may be the same or different;
- R 2 is hydrogen
- R 3 is selected from fluoro, chloro or methyl
- R 4 is selected from fluoro, chloro, bromo, cyano, amino, methyl, methoxy, methylamino, acetylamino, N-methylcarbamoyl or morpholino; m is selected from 0-2; wherein the values of R may be the same or different, or a pharmaceutically acceptable salt thereof.
- preferred compounds of the invention are any one of the Examples or a pharmaceutically acceptable salt thereof.
- preferred compounds of the invention are Examples 18, 44, 50, 56, 105, 130, 135, 163, 216 and 384 or a pharmaceutically acceptable salt thereof.
- Another aspect of the present invention provides a process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof which process (wherein variable groups are, unless otherwise specified, as defined in formula (I)) comprises of: Process a) reacting an amine of the formula (II)
- Process a) and Process b) Amines and acids may be coupled together in the presence of a suitable coupling reagent.
- Standard peptide coupling reagents known in the art can be employed as suitable coupling reagents, or for Example carbonyldiimidazole and dicyclohexyl-carbodiimide, optionally in the presence of a catalyst such as dimethylaminopyridine or 4-pyrrolidinopyridine, optionally in the presence of a base for Example triethylamine, pyridine, or 2,6-di- ⁇ /£y/-pyridines such as 2,6-lutidine or
- Suitable solvents include dimethylacetamide, dichloromethane, benzene, tetrahydrofuran and dimethylformamide.
- the coupling reaction may conveniently be performed at a temperature in the range of -40 to 40 °C.
- Suitable activated acid derivatives include acid halides, for Example acid chlorides, and active esters, for Example pentafluorophenyl esters.
- the reaction of these types of compounds with amines is well known in the art, for Example they may be reacted in the presence of a base, such as those described above, and in a suitable solvent, such as those described above.
- the reaction may conveniently be performed at a temperature in the range of -40 to 40 0 C.
- Pg is an acid protecting group, for example such as those described herein below.
- Compounds of formula (III), (V), (Ila) and (IVa) are commercially available compounds, or they are known in the literature or they may be prepared by standard processes known in the art.
- aromatic substitution reactions include the introduction of a nitro group using concentrated nitric acid, the introduction of an acyl group using, for example, an acyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions; the introduction of an alkyl group using an alkyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions; and the introduction of a halogeno group.
- modifications include the reduction of a nitro group to an amino group by for example, catalytic hydrogenation with a nickel catalyst or treatment with iron in the presence of hydrochloric acid with heating; oxidation of alkylthio to alkylsulphinyl or alkylsulphonyl.
- a suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or f-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl.
- the deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group.
- an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide.
- a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide.
- an acyl group such as a t-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulphuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris(trifluoroacetate).
- a suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine.
- a suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl.
- the deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group.
- an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide.
- a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide.
- an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon.
- a suitable protecting group for a carboxy group is, for example, an esterifying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a /-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon.
- the protecting groups may be removed at any convenient stage in the synthesis using conventional techniques well known in the chemical art.
- the compounds defined in the present invention possess anti-cancer activity which is believed to arise from the CSF-IR kinase inhibitory activity of the compounds. These properties may be assessed, for example, using the procedure set out below.
- the His-tagged kinase domain of CSF-IR i.e., amino acids 568-912, GeneBank ID NM_005211;
- the phosphorylation of the CSF-IR substrate in the presence and absence of the compound of interest was determined. Briefly, 0.2pM of purified CSF-IR, 5nM pEY substrate, and compound were preincubated in Ix buffer for 30 minutes at 25°C.
- a pharmaceutical composition which comprises a compound of the formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore, in association with a pharmaceutically-acceptable diluent or carrier.
- composition may be in a form suitable for oral administration, for example as a tablet or capsule, for parenteral injection (including intravenous, subcutaneous, intramuscular, intravascular or infusion) as a sterile solution, suspension or emulsion, for topical administration as an ointment or cream or for rectal administration as a suppository.
- parenteral injection including intravenous, subcutaneous, intramuscular, intravascular or infusion
- sterile solution emulsion
- topical administration as an ointment or cream or for rectal administration as a suppository.
- compositions may be prepared in a conventional manner using conventional excipients.
- the compound of formula (I) will normally be administered to a warm-blooded animal at a unit dose within the range 1-1000 mg/kg, and this normally provides a therapeutically-effective dose.
- a daily dose in the range of 10- 100 mg/kg is employed.
- the daily dose will necessarily be varied depending upon the host treated, the particular route of administration, and the severity of the illness being treated. Accordingly the optimum dosage may be determined by the practitioner who is treating any particular patient.
- the compounds defined in the present invention are effective anti-cancer agents which property is believed to arise from their CSF-I R kinase inhibitory properties. Accordingly the compounds of the present invention are expected to be useful in the treatment of diseases or medical conditions mediated alone or in part by CSF-IR kinase, i.e. the compounds may be used to produce a CSF-IR kinase inhibitory effect in a warm-blooded animal in need of such treatment.
- the compounds of the present invention provide a method for treating cancer characterised by inhibition of CSF-IR kinase, i.e. the compounds may be used to produce an anti-cancer effect mediated alone or in part by the inhibition of CSF-IR kinase.
- Such a compound of the invention is expected to possess a wide range of anti-cancer properties including but not limited to melanoma, papillary thyroid tumours, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukaemias, lymphoid malignancies, carcinomas and sarcomas in the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumours of the skin, colon, thyroid, lungs and ovaries.
- a compound of the formula (I), or a pharmaceutically acceptable salt thereof, as defined hereinbefore for use as a medicament is provided.
- a method for producing a CSF-IR kinase inhibitory effect in a warm-blooded animal, such as man, in need of such treatment which comprises administering to said animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined above.
- a method for producing an anti-cancer effect in a warm-blooded animal, such as man, in need of such treatment which comprises administering to said animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined above.
- a method of treating melanoma, papillary thyroid tumours, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukaemias, lymphoid malignancies, carcinomas and sarcomas in the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumours of the skin, colon, thyroid, lungs and ovaries, in a warm-blooded animal, such as man, in need of such treatment which comprises administering to said animal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined herein before.
- a pharmaceutical composition which comprises a compound of the formula (I), or a pharmaceutically acceptable salt thereof, as defined herein before in association with a pharmaceutically-acceptable diluent or carrier for use in the production of a CSF-IR kinase inhibitory effect in a warm-blooded animal such as man.
- a pharmaceutical composition which comprises a compound of the formula (I), or a pharmaceutically acceptable salt thereof, as defined herein before in association with a pharmaceutically-acceptable diluent or carrier for use in the production of an anti-cancer effect in a warm-blooded animal such as man.
- a pharmaceutical composition which comprises a compound of the formula (I), or a pharmaceutically acceptable salt thereof, as defined herein before in association with a pharmaceutically-acceptable diluent or carrier for Use in the treatment of melanoma, papillary thyroid tumours, cholangiocarcinomas, colon cancer, ovarian cancer, lung cancer, leukaemias, lymphoid malignancies, carcinomas and sarcomas in the liver, kidney, bladder, prostate, breast and pancreas, and primary and recurrent solid tumours of the skin, colon, thyroid, lungs and ovaries in a warm-blooded animal such as man.
- a compound of the formula (I), or a pharmaceutically acceptable salt thereof as defined hereinbefore in the production of a CSF-IR kinase inhibitory effect in a warm-blooded animal such as man.
- a compound of the formula (I), or a pharmaceutically acceptable salt thereof as defined hereinbefore in the production of an anti-cancer effect in a warm-blooded animal such as man.
- the CSF-IR kinase inhibitory treatment defined hereinbefore may be applied as a sole therapy or may involve, in addition to the compound of the invention, conventional surgery or radiotherapy or chemotherapy.
- Such chemotherapy may include one or more of the following categories of anti-tumour agents :- (i) antiproliferative/antineoplastic drugs and combinations thereof, as used in medical oncology, such as alkylating agents (for example cis-platin, carboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulphan and nitrosoureas); antimetabolites (for example antifolates such as fluoropyrimidines like 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside and hydroxyurea; antitumour antibiotics (for example anthracyclines like adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin and mithramycin); antimitotic agents (for example vinca alkaloids like vincristine
- Agents which inhibit cancer cell invasion for example metalloproteinase inhibitors like marimastat and inhibitors of urokinase plasminogen activator receptor function);
- inhibitors of growth factor function include growth factor antibodies, growth factor receptor antibodies (for example the anti-erbb2 antibody trastuzumab [HerceptinTM] and the anti-erbbl antibody cetuximab [C225]) , farnesyl transferase inhibitors, MEK inhibitors, tyrosine kinase inhibitors and serine/threonine kinase inhibitors, for example inhibitors of the epidermal growth factor family (for example EGFR family tyrosine kinase inhibitors such as N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3- morpholinopropoxy)quinazolin-4-amine (gefitinib, AZD 1839), N-(3-(3-(3-chloro-4-fluor
- antiangiogenic agents such as those which inhibit the effects of vascular endothelial growth factor, (for example the anti-vascular endothelial cell growth factor antibody bevacizumab [AvastinTM], compounds such as those disclosed in International Patent Applications WO 97/22596, WO 97/30035, WO 97/32856 and WO 98/13354) and compounds that work by other mechanisms (for example linomide, inhibitors of integrin ⁇ v ⁇ 3 function and angiostatin);
- vascular endothelial growth factor for example the anti-vascular endothelial cell growth factor antibody bevacizumab [AvastinTM]
- vastinTM anti-vascular endothelial cell growth factor antibody bevacizumab
- compounds that work by other mechanisms for example linomide, inhibitors of integrin ⁇ v ⁇ 3 function and angiostatin
- vascular damaging agents such as Combretastatin A4 and compounds disclosed in International Patent Applications WO 99/02166, WO00/40529, WO 00/41669, WOO 1/92224, WO02/04434 and WO02/08213;
- antisense therapies for example those which are directed to the targets listed above, such as ISIS 2503, an anti-ras antisense;
- gene therapy approaches including for example approaches to replace aberrant genes such as aberrant p53 or aberrant BRCAl or, BRCA2, GDEPT (gene-directed enzyme pro-drug therapy) approaches such as those using cytosine deaminase, thymidine kinase or a bacterial nitroreductase enzyme and approaches to increase patient tolerance to chemotherapy or radiotherapy such as multi-drug resistance gene therapy;
- GDEPT gene-directed enzyme pro-drug therapy
- immunotherapy approaches including for example ex-vivo and in-vivo approaches to increase the immunogenicity of patient tumour cells, such as transfection with cytokines such as interleukin 2, interleukin 4 or granulocyte-macrophage colony stimulating factor, approaches to decrease T-cell anergy, approaches using transfected immune cells such as cytokine-transfected dendritic cells, approaches using cytokine-transfected tumour cell lines and approaches using anti-idiotypic antibodies;
- Cell cycle inhibitors including for example CDK inhibitiors (eg flavopiridol) and other inhibitors of cell cycle checkpoints (eg checkpoint kinase); inhibitors of aurora kinase and other kinases involved in mitosis and cytokinesis regulation (eg mitotic kinesins); and histone deacetylase inhibitors; and
- endothelin antagonists including endothelin A antagonists, endothelin B antagonists and
- Such conjoint treatment may be achieved by way of the simultaneous, sequential or separate dosing of the individual components of the treatment.
- Such combination products employ the compounds of this invention within the dosage range described hereinbefore and the other pharmaceutically-active agent within its approved dosage range.
- the compounds of formula (I) and their pharmaceutically acceptable salts are also useful as pharmacological tools in the development and standardisation of in vitro and in vivo test systems for the evaluation of the effects of inhibitors of CSF-IR kinase in laboratory animals such as cats, dogs, rabbits, monkeys, rats and mice, as part of the search for new therapeutic agents.
- temperatures are given in degrees Celsius ( 0 C); operations were carried out at room or ambient temperature, that is, at a temperature in the range of 18-25°C;
- organic solutions were dried over anhydrous sodium sulphate; evaporation of solvent was carried out using a rotary evaporator under reduced pressure (600-4000 Pascals; 4.5-30 mmHg) with a bath temperature of up to 60 0 C;
- NMR data is in the form of delta values for major diagnostic protons, given in parts per million (ppm) relative to tetramethylsilane (TMS) as an internal standard, determined at 400 MHz using perdeuterio dimethyl sulphoxide (DMSO-d 6 ) as solvent unless otherwise indicated;
- ISCO refers to normal phase flash column chromatography using 12 g and 40 g prepacked silica gel cartridges used according to the manufacturers instruction obtained from ISCO, Inc, 4700 superior street Lincoln, NE, USA.;
- Glass HPLC refers to a YMC-AQC 18 reverse phase HPLC Column with dimension 30 20 mm/100 and 50 mm/250 in water/MeCN with 0.1 % TFA as mobile phase, obtained
- Parr Hydrogenator or Parr shaker type hydrogenators are systems for treating chemicals with hydrogen in the presence of a catalyst at pressures up to 5 atmospheres (60 psig) and temperatures to 80 0 C.
- Example 1 Parr Hydrogenator or Parr shaker type hydrogenators are systems for treating chemicals with hydrogen in the presence of a catalyst at pressures up to 5 atmospheres (60 psig) and temperatures to 80 0 C.
- Example 55 The following compounds were prepared by the procedure in Example 1 using 5- amino-2-methyl-N-pyridin-3-ylbenzamide (Method 68) or 5-amino-2-chloro-N-(5- fluoropyridin-3-yl)benzamide for (Method 79) Example 55 and the appropriate SM. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- Example 121 The following compounds were prepared by the procedure in Example 121 using 5- amino-2-chloro-iV-pyridin-3-ylbenzamide (Method 76) and the appropriate SM with the exception of Example 165 which was prepared from 2-chloro-5- ⁇ [3-(trifluoromethyl)benzoyl] amino ⁇ benzoic acid (Method 224) and JV-(5-aminopyridin-2-yl)acetamide. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- Example 166 The following compounds were prepared by the procedure in Example 166 using 5- amino-2-fluoro-jV-pyridin-3-ylbenzamide (Method 75) and the appropriate SM. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- Example 183 The following compounds were prepared by the procedure in Example 183 using the appropriate SMs. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- the tube was heated in microwave (Smith, Personal ChemistryTM) and heated at 180°C for 2000 seconds.
- the solution was filtered, and separated between EtOAc and water. Organic layer was dried and evaporated under reduced pressure.
- the crude product was purified by reverse phase ⁇ PLC (5-75% MeCN/ ⁇ 2 O, 15 min) and the title compound (75.6 mg, 30%) was collected by evaporation.
- the resulting reaction mixture was warmed to 80 °C and was allowed to stir for 12 h before being cooled and diluted with EtOAc ( ⁇ 100 ml).
- the organic phase was poured into a separator funnel and washed with saturated aqueous NaHCO 3 ( ⁇ 100 ml).
- the organic extract was dried with MgSO 4 , filtered, and concentrated in vacuo to yield the crude product, which was purified on a 40 g SiO 2 column using MeOH/EtOAc (1 :10) as eluent giving 144 mg (77%) of the title compound as a white solid.
- N-(S- 5 bromopyridin-3-yl)-2-methyl-5- ⁇ f3-(trifluoromethyl)benzoyl]amino) benzamide (Example 193; 200 mg, 0.418 mmol) and MeCN (1.75 ml).
- Et 3 N (0.293 ml, 2.10 mmol) was added followed by prop-2-yn-l -amine (58 mg, 1.05 mmol), CuI ( 25 mg, 0.125 mmol), and Pd(PPh 3 ) 4 (96 mg, 0.084 mmol).
- the reaction was warmed to 50 0 C with stirring for 12 h before being cooled to room temperature, diluted with 50 ml of EtOAc, and filtered through a
- the reaction was allowed to stir for 12 h at room temperature before being purged with argon, diluted with ⁇ 15 ml of EtOAc 5 and filtered through a pad of SiO 2 .
- the SiO 2 pad was rinsed with an additional 25 ml of EtOAc and the combined filtrate was concentrated in vacuo to yield the crude product, which was purified on a 40 g SiO 2 column using EtOAc as eluent giving 44 mg (98%) of the title compound as an off-white solid.
- Example 341 The following compounds were prepared by the procedure in Example 341 and the appropriate SM. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- Examples 345-351 The following compounds were prepared by the procedure in Example 344 using the appropriate SMs. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- Example 244 N- (5-aminopyridin-3-yl)-2-methyl-5- ⁇ f3-(trifluoromethyl)benzoyl]amino) benzamide (Example 244), and the appropriate SM. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- Example 202 The following compound was prepared by the procedure in Example 357, using 7V-(6- aminopyridin-3-yl)-5- ⁇ [3-(l-cyano-l-methylethyl)benzoyl]amino ⁇ -2-methylbenzamide (Example 202) and the appropriate SM. Further purification was required (column chromatography utilizing an ISCO system).
- Example 359 i ⁇ -f5-(Acetylamino ' )pyridin-3-vn-2-methyl-5- ⁇ f3-(trifluoromethyl)benzoyl1amino ⁇ benzamide
- N-(5- aminopyridin-3-yl)-2-methyl-5- ⁇ [3-(trifluoromethyl)benzoyl]amino ⁇ benzamide (Example 244; 200 mg, 0.482 mmol).
- Pyridine 5.0 ml
- acetyl chloride 0.044 ml, 0.603 mmol
- Example 202 N-(6- aminopyridin-3-yl)-5- ⁇ f3-(l-cyano-l-methylethyl)benzoyl]amino ⁇ -2-methylbenzamide (Example 202) and the appropriate SM. In some cases, further purification was required (supercritical fluid, Gilson reverse phase preparatory HPLC or column chromatography utilizing an ISCO system).
- N-(5-Aminopyridm-3-yl)-5- ⁇ [3-(l-cyano-l-methylethyl)benzoyl]amino ⁇ -2- methylbenzamide (Example 205; 164 mg, 0.398 mmol) was combined with acetone and sodium triacetoxyborohydride (337 mg, 1.59 mmol) in 0.80 ml of THF and heated at 30°C in a sealed tube overnight. LC/MS confirmed the formation of the product and the mixture was partitioned between H 2 O and EtOAc. The organic layer was washed with brine and dried with MgSO 4 .
- Methods 76-82 The following compounds were prepared by the procedure of Method 75, using the appropriate starting material.
- reaction mixture was extracted with EtOAc (2 x 250 ml) and the combined organic phase was dried with MgSO 4 and concentrated in vacuo to yield the crude reaction product which was purified on 120 g SiO 2 using hexanes/EtOAc 10:1 as eluent giving 3.70 g of the title compound as a yellow oil (76 %) m/z 447.
- reaction mixture was extracted with EtOAc (2 x 50 ml) and the combined organic phase was dried with MgSO 4 and concentrated in vacuo to yield the crude reaction product which was purified on 40 g SiO 2 using hexanes/EtOAc 2:1 as eluent giving 0.270 g of the title compound as a colourless oil (71 %) m/z 182.
- Triethylamine (0.718 g, 7.40 mmol) was then added and the reaction was allowed to warm to 25 °C with stirring over 1 h before being quenched with NaHCO 3(sat ) (250 ml).
- the reaction mixture was then extracted with EtOAc (2 x 50 ml) and the combined organic phase was dried with MgSO 4 and concentrated in vacuo to yield the crude reaction product which was purified on 40 g SiO 2 using hexanes/EtOAc 10:1 as eluent giving 0.262 g of the title compound as a colourless oil (99 %) m/z 180.
- Method 119 The following compounds were prepared by the procedure of Method 1 18, using the appropriate starting material.
- 5-Amino-N-methylnicotinamide A solution of 5-aminonicotinic acid (414 mg, 3 mmol), DIEA (1.57 ml, 9 mmol) and methyl amine (2.0 M in THF, 4.5 ml, 9 mmol) in DMF (10 ml) was treated with HATU (1.71 g, 4.5 mmol). The reaction was stirred for 5 h and then quenched with H 2 O (30 ml). The reaction mixture was extracted with EtOAc (50 ml), washed with NaCl (sat) (20 ml) and dried with MgSO 4 . The organics were removed under reduced pressure; m/z 151.
- Method 161 The following compounds were prepared by the procedure of Method 160, using the appropriate starting material.
- DeoxoFluorTM was stirred overnight at 85 0 C. The reaction was allowed to cool to room temperature and quenched with brine. The mixture was poured into a separator funnel and extracted with EtOAc. The organic extract was dried over Na 2 SO 4 , filtered, and concentrated in vacuo to yield the crude product. The crude oil was then subjected to ISCO purification using EtOAc/hexanes (1 :4) as eluent to yield 396 mg (50%) of the title compound as a colourless oil.
- 2-amino-3-chloro-5- nitropyridine was obtained (10.8 g, 62%) and it was used in the next step without further purification. M/z 175.
- 2-amino-3-chloro-5-nitropyridine (8.72g, 50mmol) was dissolved in MeOH (125 ml).
- a solution of ammonium chloride (13.5 g, 250mmol) in H 2 O (125 ml) were added, followed by 14g of iron powder.
- the solution was stirred with mechanic stirring at 78 °C for 2 hours.
- the solution was filtered at 50 0 C and the isolated solid was washed by hot MeOH.
- the solvent was evaporated by vacuum and the crude product was extracted by acetone and filtered.
- Method 187 The following compound was prepared by the procedure of Method 186, using the appropriate starting material.
- N-(2- ⁇ ttert-butyl(dimethyl)silyl]oxy ⁇ ethyl)-5-nitropyridin-2-amine (Method 156; 1.29 g, 4.34 mmol) was dissolved in 20 ml of MeOH and 260 mg of palladium (10 wt. % on activated carbon-Degussa®) was added. The reaction was subjected to 1 atmosphere of hydrogen overnight. LC/MS confirmed the formation of the product. The reaction mixture was filtered through diatomaceous earth and washed with MeOH and EtOAc. The title compound (970 mg) was collected by evaporation as a thick red oil. M/z 268.
- 3-(l-Cvano-l ,2-dimethylpropyl)benzoic acid To a solution of 3-(l-cyanoethyl)benzoic acid (500 mg) in THF (50ml) at -78°C was added slowly a solution of LiHMDS (60ml, 1.0M in THF) and the resulting red solution was allowed to stir at his temperature for 30 minutes. Isopropyl iodide (10 ml) was added slowly and the resulting mixture was warmed up to room temperature and stirred for 10 hours. The mixture was partitioned between EtOAc and H 2 O and the aqueous layer was acidified with IN HCl until pH 3.
- LiHMDS 60ml, 1.0M in THF
- Methyl 1 ,3,3-trimethyl-2-oxoindoline-5-carboxylate To a solution of methyl 2-oxoindoline-5-carboxylate (400 mg, 2.09 mmol) in THF (10 ml) at -78 0 C was added LiHMDS (1.0 M, 16.7 ml, 16.75 mmol) and MeI (1.3 ml, 20.9 mmol). The reaction was allowed to stir overnight to room temperature. The reaction was then quenched with ⁇ 25 ml aqueous NH 4 Cl.
- Methyl 5- ⁇ [3-(l-cyano-l-methylethyl)benzoyl]amino ⁇ -2- chlorobenzoate was collected by evaporation as a reddish-brown oil.
- Methyl 5- ⁇ [3-(l-cyano-l-methylethyl)benzoyl]amino ⁇ -2-chlorobenzoate 120 mg was dissolved in a 3:1 :1 (v/v/v) solution of THF/MeOH/H 2 O and lithium hydroxide (50 ing) was added slowly. The reaction was then stirred overnight at 25°C. LC/MS confirmed the formation of the product. The organic solvents were evaporated and the remaining material was separated between EtOAc and H 2 O.
- the aqueous layer was collected and acidified to a pH of between 3 and 4 with 2N HCl.
- the mixture was partitioned between H 2 O and EtOAc, and the organic layer was washed with brine and dried with MgSO 4 .
- the title compound (85 mg) was collected by evaporation as a white solid.
- Methyl 3-[(2-cyano-lH-pyrrol-l-yl)methyl]benzoate (300 mg) was dissolved in MeO ⁇ / ⁇ 2 O (10 ml, 3:1 v/v) and LiOH (60 mg) was added. The resulting mixture was stirred at room temperature for 10 hours. The aqueous phase was filtered and washed with EtOAc. The basic aqueous layer was acidified by the addition of IN HCl until pH 3. The aqueous layer was extracted with EtOAc (3x) and then dried with Na 2 SO 4(S ). Evaporation of the solvent afforded the title compound as a white solid (210 mg); m/z 226.
- the reaction was heated to 80 0 C with stirring for 5 h before being cooled to room temperature and quenched with ⁇ 200 ml saturated aqueous NaHCO 3 .
- the mixture was poured into a separator funnel and extracted with ⁇ 200 ml of EtOAc.
- the combined organic extract was dried with MgSO 4 , filtered, and concentrated in vacuo to yield the crude product, which was purified on a 120 g SiO 2 column using hexanes/EtOAc (9:1) as eluent giving 5.26 g (82%) of the title compound as a white solid m/z 527.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998022103A1 (en) * | 1996-11-16 | 1998-05-28 | Zeneca Limited | Raf kinase inhibitors |
WO2000055120A1 (en) * | 1999-03-17 | 2000-09-21 | Astrazeneca Ab | Amide derivatives |
WO2006003387A1 (en) * | 2004-06-30 | 2006-01-12 | Reckitt Benckiser N.V. | Improvements in and relating to packaging |
-
2005
- 2005-12-22 WO PCT/GB2005/004985 patent/WO2006067445A2/en not_active Application Discontinuation
- 2005-12-22 TW TW094145875A patent/TW200635899A/en unknown
- 2005-12-22 AR ARP050105491A patent/AR053992A1/en not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998022103A1 (en) * | 1996-11-16 | 1998-05-28 | Zeneca Limited | Raf kinase inhibitors |
WO2000055120A1 (en) * | 1999-03-17 | 2000-09-21 | Astrazeneca Ab | Amide derivatives |
WO2006003387A1 (en) * | 2004-06-30 | 2006-01-12 | Reckitt Benckiser N.V. | Improvements in and relating to packaging |
Non-Patent Citations (2)
Title |
---|
BARTULEWICZ D ET AL: "Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety" EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 36, no. 5, May 2001 (2001-05), pages 461-467, XP004372857 ISSN: 0223-5234 * |
BARTULEWICZ D ET AL: "SYNTHETIC ANALOGUES OF NETROPSIN AND DISTAMYCIN - SYNTHESIS OF A NEW PYRIDINE AND CARBOCYCLIC ANALOGUES OF THE PYRROLECARBOXAMIDE ANTITUMOUR ANTIBIOTICS" ACTA BIOCHIMICA POLONICA, POLISH SCIENTIFIC PUBLISHERS, WARSAW, PO, vol. 1, no. 45, 1998, pages 41-57, XP001064599 ISSN: 0001-527X * |
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USRE50030E1 (en) | 2013-12-13 | 2024-07-02 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
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EP3079682A4 (en) * | 2013-12-13 | 2017-08-30 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
US10633348B2 (en) | 2013-12-13 | 2020-04-28 | Dana-Farber Cancer Institute, Inc. | Methods to treat lymphoplasmacytic lymphoma |
US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9181288B2 (en) | 2014-01-16 | 2015-11-10 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9873671B2 (en) | 2014-01-16 | 2018-01-23 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9505722B2 (en) | 2014-01-16 | 2016-11-29 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9339510B2 (en) | 2014-01-16 | 2016-05-17 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US10632112B2 (en) | 2014-02-05 | 2020-04-28 | Novira Therapeutics, Inc. | Combination therapy for treatment of HBV infections |
US10213420B2 (en) | 2014-02-05 | 2019-02-26 | Novira Therapeutics, Inc. | Combination therapy for treatment of HBV infections |
US11078193B2 (en) | 2014-02-06 | 2021-08-03 | Janssen Sciences Ireland Uc | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
WO2015131031A1 (en) | 2014-02-28 | 2015-09-03 | Incyte Corporation | Jak1 inhibitors for the treatment of myelodysplastic syndromes |
US9400280B2 (en) | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
US10112957B2 (en) | 2014-10-22 | 2018-10-30 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
US10844077B2 (en) | 2014-10-22 | 2020-11-24 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
US10464949B2 (en) | 2014-10-22 | 2019-11-05 | Dana-Farber Cancer Institute, Inc. | Thiazolyl-containing compounds for treating proliferative diseases |
US9884831B2 (en) | 2015-03-19 | 2018-02-06 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis B infections |
US10537580B2 (en) | 2015-03-19 | 2020-01-21 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis B infections |
US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
US11858939B2 (en) | 2015-07-06 | 2024-01-02 | Alkermes, Inc. | Hetero-halo inhibitors of histone deacetylase |
US10421756B2 (en) | 2015-07-06 | 2019-09-24 | Rodin Therapeutics, Inc. | Heterobicyclic N-aminophenyl-amides as inhibitors of histone deacetylase |
US10919902B2 (en) | 2015-07-06 | 2021-02-16 | Alkermes, Inc. | Hetero-halo inhibitors of histone deacetylase |
US10077239B2 (en) | 2015-09-29 | 2018-09-18 | Novira Therapeutics, Inc. | Crystalline forms of a hepatitis B antiviral agent |
US10954220B2 (en) | 2016-03-09 | 2021-03-23 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
US20190071400A1 (en) * | 2016-03-09 | 2019-03-07 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
EP3426244A4 (en) * | 2016-03-09 | 2019-11-06 | Raze Therapeutics Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
US11014882B2 (en) | 2016-03-09 | 2021-05-25 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
US11535593B2 (en) | 2016-03-09 | 2022-12-27 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
EP4234552A3 (en) * | 2016-03-09 | 2023-10-18 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
US11634412B2 (en) | 2016-03-09 | 2023-04-25 | Raze Therapeutics, Inc. | 3-phosphoglycerate dehydrogenase inhibitors and uses thereof |
US11129834B2 (en) | 2016-04-15 | 2021-09-28 | Novira Therapeutics, Inc. | Combinations and methods comprising a capsid assembly inhibitor |
US10441589B2 (en) | 2016-04-15 | 2019-10-15 | Novira Therapeutics, Inc. | Combinations and methods comprising a capsid assembly inhibitor |
US10633375B2 (en) | 2016-08-31 | 2020-04-28 | Jinagsu Hengrui Medicine Co., Ltd | Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof |
US11084808B2 (en) | 2016-08-31 | 2021-08-10 | Jiangsu Hengrui Medicine Co., Ltd. | Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof |
US10519149B2 (en) | 2017-01-11 | 2019-12-31 | Rodin Therapeutics, Inc. | Bicyclic inhibitors of histone deacetylase |
US10696673B2 (en) | 2017-01-11 | 2020-06-30 | Rodin Therapeutics, Inc. | Bicyclic inhibitors of histone deacetylase |
US11286256B2 (en) | 2017-01-11 | 2022-03-29 | Alkermes, Inc. | Bicyclic inhibitors of histone deacetylase |
US10793567B2 (en) | 2017-01-11 | 2020-10-06 | Rodin Therapeutics, Inc. | Bicyclic inhibitors of histone deacetylase |
US11225479B2 (en) | 2017-01-11 | 2022-01-18 | Alkermes, Inc. | Bicyclic inhibitors of histone deacetylase |
US9951069B1 (en) | 2017-01-11 | 2018-04-24 | Rodin Therapeutics, Inc. | Bicyclic inhibitors of histone deacetylase |
US11987580B2 (en) | 2017-01-11 | 2024-05-21 | Alkermes, Inc. | Bicyclic inhibitors of histone deacetylase |
RU2765785C2 (en) * | 2017-05-24 | 2022-02-02 | Аббиско Тхерапеутицс Цо., Лтд. | N-(azaaryl)cyclolactam-1-carboxamide derivative, its preparation method and its application |
AU2018274043C1 (en) * | 2017-05-24 | 2021-08-19 | Abbisko Therapeutics Co., Ltd. | N-(azaaryl)cyclolactam-1-carboxamide derivative, preparation method therefor, and use thereof |
AU2018274043B2 (en) * | 2017-05-24 | 2020-10-08 | Abbisko Therapeutics Co., Ltd. | N-(azaaryl)cyclolactam-1-carboxamide derivative, preparation method therefor, and use thereof |
WO2018214867A1 (en) * | 2017-05-24 | 2018-11-29 | 上海和誉生物医药科技有限公司 | N-(azaaryl)cyclolactam-1-carboxamide derivative, preparation method therefor, and use thereof |
US11149021B2 (en) | 2017-05-24 | 2021-10-19 | Abbisko Therapeutics Co., Ltd. | N-(azaaryl)cyclolactam-1-carboxamide derivative, preparation method therefor, and use thereof |
US10647661B2 (en) | 2017-07-11 | 2020-05-12 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
US11603351B2 (en) | 2017-07-11 | 2023-03-14 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
US11225475B2 (en) | 2017-08-07 | 2022-01-18 | Alkermes, Inc. | Substituted pyridines as inhibitors of histone deacetylase |
US11912702B2 (en) | 2017-08-07 | 2024-02-27 | Alkermes, Inc. | Substituted pyridines as inhibitors of histone deacetylase |
US11278541B2 (en) | 2017-12-08 | 2022-03-22 | Incyte Corporation | Low dose combination therapy for treatment of myeloproliferative neoplasms |
US10596161B2 (en) | 2017-12-08 | 2020-03-24 | Incyte Corporation | Low dose combination therapy for treatment of myeloproliferative neoplasms |
US10899736B2 (en) | 2018-01-30 | 2021-01-26 | Incyte Corporation | Processes and intermediates for making a JAK inhibitor |
US10973801B2 (en) | 2018-03-14 | 2021-04-13 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
US11304949B2 (en) | 2018-03-30 | 2022-04-19 | Incyte Corporation | Treatment of hidradenitis suppurativa using JAK inhibitors |
WO2020002563A1 (en) | 2018-06-29 | 2020-01-02 | Syngenta Participations Ag | Pesticidally active azole-amide compounds |
US11096931B2 (en) | 2019-02-22 | 2021-08-24 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
WO2020182649A1 (en) | 2019-03-08 | 2020-09-17 | Syngenta Crop Protection Ag | Pesticidally active azole-amide compounds |
WO2020188027A1 (en) | 2019-03-20 | 2020-09-24 | Syngenta Crop Protection Ag | Pesticidally active azole amide compounds |
WO2020193341A1 (en) | 2019-03-22 | 2020-10-01 | Syngenta Crop Protection Ag | N-[1-(5-bromo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxamide derivatives and related compounds as insecticides |
WO2020201079A1 (en) | 2019-03-29 | 2020-10-08 | Syngenta Crop Protection Ag | Pesticidally active diazine-amide compounds |
WO2020201398A1 (en) | 2019-04-05 | 2020-10-08 | Syngenta Crop Protection Ag | Pesticidally active diazine-amide compounds |
US11491148B2 (en) | 2019-05-06 | 2022-11-08 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
WO2021026436A1 (en) | 2019-08-08 | 2021-02-11 | Agios Pharmaceuticals, Inc. | A method for preparing ivosidenib and an intermediate thereof |
WO2021037614A1 (en) | 2019-08-23 | 2021-03-04 | Syngenta Crop Protection Ag | Pesticidally active pyrazine-amide compounds |
WO2021122645A1 (en) | 2019-12-20 | 2021-06-24 | Syngenta Crop Protection Ag | Pesticidally active azole-amide compounds |
WO2021170881A1 (en) | 2020-02-27 | 2021-09-02 | Syngenta Crop Protection Ag | Pesticidally active diazine-bisamide compounds |
US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
WO2022247786A1 (en) * | 2021-05-24 | 2022-12-01 | 上海和誉生物医药科技有限公司 | Acid salt of crystalline csf-1r inhibitor, and preparation method therefor and use thereof |
WO2022258481A1 (en) | 2021-06-09 | 2022-12-15 | Syngenta Crop Protection Ag | Pesticidally active diazine-amide compounds |
CN115724791A (en) * | 2022-10-10 | 2023-03-03 | 安徽金禾化学材料研究所有限公司 | Preparation method of 2-methyl-3-nitro-5-aminopyridine |
CN115611806A (en) * | 2022-11-08 | 2023-01-17 | 江苏中旗科技股份有限公司 | Preparation method of 4-trifluoromethyl-3-cyanopyridine |
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