IL307868A - Compounds for use in the treatment of hyperproliferative disorders - Google Patents
Compounds for use in the treatment of hyperproliferative disordersInfo
- Publication number
- IL307868A IL307868A IL307868A IL30786823A IL307868A IL 307868 A IL307868 A IL 307868A IL 307868 A IL307868 A IL 307868A IL 30786823 A IL30786823 A IL 30786823A IL 307868 A IL307868 A IL 307868A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- thiazol
- indol
- methyl
- acetamide
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims 19
- 230000003463 hyperproliferative effect Effects 0.000 title claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 62
- -1 C 1-4-alkyl Chemical group 0.000 claims 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 10
- 239000001257 hydrogen Substances 0.000 claims 10
- 125000004122 cyclic group Chemical group 0.000 claims 9
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- IDBDFZFJOFJNPY-UHFFFAOYSA-N 2-imidazo[2,1-b][1,3]thiazol-6-yl-n-[4-(2-methyl-1h-indol-3-yl)-1,3-thiazol-2-yl]acetamide Chemical compound C1=CC=C2C(C=3N=C(NC(=O)CC=4N=C5SC=CN5C=4)SC=3)=C(C)NC2=C1 IDBDFZFJOFJNPY-UHFFFAOYSA-N 0.000 claims 2
- JOGQECBGGWGCJS-UHFFFAOYSA-N 3-(1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)-1,3-thiazol-2-yl]propanamide Chemical compound C1=CC=C2C(CCC(=O)NC=3SC=C(N=3)C=3C4=CC=CC=C4NC=3C)=CNC2=C1 JOGQECBGGWGCJS-UHFFFAOYSA-N 0.000 claims 2
- MNBQOGHQUOTRBI-UHFFFAOYSA-N CC(C(N(C)C1=NC(C2=C(C)NC3=CC=CC=C23)=CS1)=O)C1=CN(C=CS2)C2=N1 Chemical compound CC(C(N(C)C1=NC(C2=C(C)NC3=CC=CC=C23)=CS1)=O)C1=CN(C=CS2)C2=N1 MNBQOGHQUOTRBI-UHFFFAOYSA-N 0.000 claims 2
- LVGQBVQRQDXSHF-UHFFFAOYSA-N CC(NC1=C2)=C(C3=CSC(NC(CC4=CN(C=CS5)C5=N4)=O)=N3)C1=CC=C2F Chemical compound CC(NC1=C2)=C(C3=CSC(NC(CC4=CN(C=CS5)C5=N4)=O)=N3)C1=CC=C2F LVGQBVQRQDXSHF-UHFFFAOYSA-N 0.000 claims 2
- XJOHRKQFLSPSHR-UHFFFAOYSA-N CC(NC1=CC=CC=C11)=C1C1=C(C)SC(NC(CC2=CN(C=CS3)C3=N2)=O)=N1 Chemical compound CC(NC1=CC=CC=C11)=C1C1=C(C)SC(NC(CC2=CN(C=CS3)C3=N2)=O)=N1 XJOHRKQFLSPSHR-UHFFFAOYSA-N 0.000 claims 2
- UVVVTCOLTKGWLG-UHFFFAOYSA-N CC(NC1=CC=CC=C11)=C1C1=C(F)SC(NC(CC2=CN(C=CS3)C3=N2)=O)=N1 Chemical compound CC(NC1=CC=CC=C11)=C1C1=C(F)SC(NC(CC2=CN(C=CS3)C3=N2)=O)=N1 UVVVTCOLTKGWLG-UHFFFAOYSA-N 0.000 claims 2
- YKBBMFSQWGNPPH-UHFFFAOYSA-N CC(S1)=CN2C1=NC(CC(NC1=NC(C3=C(C)NC4=CC=CC=C34)=CS1)=O)=C2 Chemical compound CC(S1)=CN2C1=NC(CC(NC1=NC(C3=C(C)NC4=CC=CC=C34)=CS1)=O)=C2 YKBBMFSQWGNPPH-UHFFFAOYSA-N 0.000 claims 2
- ITIWQPRNCJSDPR-UHFFFAOYSA-N CC1=C(C2=COC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=COC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC=CC=C2N1 ITIWQPRNCJSDPR-UHFFFAOYSA-N 0.000 claims 2
- NPRCJUQAOZEYHH-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC(C3=C4)=CNC3=CC=C4F)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC(C3=C4)=CNC3=CC=C4F)=O)=N2)C2=CC=CC=C2N1 NPRCJUQAOZEYHH-UHFFFAOYSA-N 0.000 claims 2
- CNZQKPDGTGILMB-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC(C3=C4)=CNC3=CC=C4O)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC(C3=C4)=CNC3=CC=C4O)=O)=N2)C2=CC=CC=C2N1 CNZQKPDGTGILMB-UHFFFAOYSA-N 0.000 claims 2
- CHHAMDNJEXEPTM-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC(C3=C4)=CNC3=CC=C4OC)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC(C3=C4)=CNC3=CC=C4OC)=O)=N2)C2=CC=CC=C2N1 CHHAMDNJEXEPTM-UHFFFAOYSA-N 0.000 claims 2
- RMGDNQLJYGIFBW-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CC(Br)=CS3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CC(Br)=CS3)=O)=N2)C2=CC=CC=C2N1 RMGDNQLJYGIFBW-UHFFFAOYSA-N 0.000 claims 2
- AZJROIGJIKGFCR-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CC(C=CC=C4)=C4O3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CC(C=CC=C4)=C4O3)=O)=N2)C2=CC=CC=C2N1 AZJROIGJIKGFCR-UHFFFAOYSA-N 0.000 claims 2
- CRZCZRGSFYNNBF-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CC4=CC=CC=C4N3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CC4=CC=CC=C4N3)=O)=N2)C2=CC=CC=C2N1 CRZCZRGSFYNNBF-UHFFFAOYSA-N 0.000 claims 2
- XDUMJTPLBZMVAJ-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CN(C)C4=CC=CC=C34)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CN(C)C4=CC=CC=C34)=O)=N2)C2=CC=CC=C2N1 XDUMJTPLBZMVAJ-UHFFFAOYSA-N 0.000 claims 2
- WKDKLNBAOUYOIM-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CN(C=C(C=C4)F)C4=N3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CN(C=C(C=C4)F)C4=N3)=O)=N2)C2=CC=CC=C2N1 WKDKLNBAOUYOIM-UHFFFAOYSA-N 0.000 claims 2
- RZFFLWVRNXPJQM-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC(N)=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC(N)=CC=C2N1 RZFFLWVRNXPJQM-UHFFFAOYSA-N 0.000 claims 2
- RYZODVQMJCFVST-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC(OC)=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC(OC)=CC=C2N1 RYZODVQMJCFVST-UHFFFAOYSA-N 0.000 claims 2
- KIFKHVHNYDBQNZ-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC([N+]([O-])=O)=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CN(C=CS4)C4=N3)=O)=N2)C2=CC([N+]([O-])=O)=CC=C2N1 KIFKHVHNYDBQNZ-UHFFFAOYSA-N 0.000 claims 2
- GVYHQRCGRWHASH-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CNC4=CC(Cl)=CC=C34)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CNC4=CC(Cl)=CC=C34)=O)=N2)C2=CC=CC=C2N1 GVYHQRCGRWHASH-UHFFFAOYSA-N 0.000 claims 2
- OFOSQCGPIKARPR-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CNC4=CC=CC=C34)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CNC4=CC=CC=C34)=O)=N2)C2=CC=CC=C2N1 OFOSQCGPIKARPR-UHFFFAOYSA-N 0.000 claims 2
- PWARUKNSNOVTDN-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CNC=N3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CNC=N3)=O)=N2)C2=CC=CC=C2N1 PWARUKNSNOVTDN-UHFFFAOYSA-N 0.000 claims 2
- YOBYRGFRBBFUQD-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=CSC4=NC=CN34)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=CSC4=NC=CN34)=O)=N2)C2=CC=CC=C2N1 YOBYRGFRBBFUQD-UHFFFAOYSA-N 0.000 claims 2
- HZJXPROVZLZGTQ-UHFFFAOYSA-N CC1=C(C2=CSC(NC(CC3=NC(C=CC=C4)=C4O3)=O)=N2)C2=CC=CC=C2N1 Chemical compound CC1=C(C2=CSC(NC(CC3=NC(C=CC=C4)=C4O3)=O)=N2)C2=CC=CC=C2N1 HZJXPROVZLZGTQ-UHFFFAOYSA-N 0.000 claims 2
- BMJHRBBKVWNMQW-UHFFFAOYSA-N CC1=C(CC(NC2=NC(C3=C(C)NC4=CC=CC=C34)=CS2)=O)SC2=C1C=CC=C2 Chemical compound CC1=C(CC(NC2=NC(C3=C(C)NC4=CC=CC=C34)=CS2)=O)SC2=C1C=CC=C2 BMJHRBBKVWNMQW-UHFFFAOYSA-N 0.000 claims 2
- FDARGIXVWGRVQR-UHFFFAOYSA-N CC1=CC=C2NC=C(C3=CSC(NC(CC4=CN(C=CS5)C5=N4)=O)=N3)C2=C1 Chemical compound CC1=CC=C2NC=C(C3=CSC(NC(CC4=CN(C=CS5)C5=N4)=O)=N3)C2=C1 FDARGIXVWGRVQR-UHFFFAOYSA-N 0.000 claims 2
- ZRJNPVQQLYVRDF-UHFFFAOYSA-N CC1=CSC2=NC(CC(NC3=NC(C4=C(C)NC5=CC=CC=C45)=CS3)=O)=CN12 Chemical compound CC1=CSC2=NC(CC(NC3=NC(C4=C(C)NC5=CC=CC=C45)=CS3)=O)=CN12 ZRJNPVQQLYVRDF-UHFFFAOYSA-N 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- YRIJACZWRDOSBS-UHFFFAOYSA-N O=C(CC1=CN(C=CS2)C2=N1)NC1=NC(C2=CNC3=CC=CC(Br)=C23)=CS1 Chemical compound O=C(CC1=CN(C=CS2)C2=N1)NC1=NC(C2=CNC3=CC=CC(Br)=C23)=CS1 YRIJACZWRDOSBS-UHFFFAOYSA-N 0.000 claims 2
- WFRZZZBXKCOVCE-UHFFFAOYSA-N [O-][N+](C1=CC=C2NC=C(C3=CSC(NC(CC4=CN(C=CS5)C5=N4)=O)=N3)C2=C1)=O Chemical compound [O-][N+](C1=CC=C2NC=C(C3=CSC(NC(CC4=CN(C=CS5)C5=N4)=O)=N3)C2=C1)=O WFRZZZBXKCOVCE-UHFFFAOYSA-N 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 239000011737 fluorine Chemical group 0.000 claims 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (17)
1. A compound of formula (I) CN G N OR R (CH)n RGCCNHC AAAA R (I) wherein n is 0 or 1; G is an heteroaromatic ring system comprising a five membered ring attached to the (CH2)n group, in which the five membered ring is optionally condensed with other rings, wherein said heteroaromatic ring system may comprise 1 to 3 atoms selected from O, S and N in the ring system and said ring system is: a) unsubstituted, b) C-substituted with 1-3 substituents selected from the group consisting of halogen atoms, C1-4-alkyl, C1-4-alkoxy, C1-4-alkyl-NH-, C1-4-alkyl-S-, C1-4-alkyl-SO-, C1-4-alkyl-SO2-, C2-4-alkynyl, C3-4-alkynyl-O-, C3-4-alkynyl-NH-, C3-4-alkynyl-S-, -OH, HO-C1-4-alkyl, C1-2-alkyl-O-C1-4-alkyl-, -NH2, H2N-C1-4-alkyl, C1-2-alkyl-NH-C1-4-alkyl-, -SH, HS-C1-4-alkyl, C1-2-alkyl-S-C1-4-alkyl-, -CN, NC-C1-4-alkyl, -COOH, HOOC-C1-4-alkyl, -COO-C1-2-alkyl, C1-2-alkyl-OCO-C1-4- alkyl-, -CONH2, H2NCO-C1-4-alkyl, -CONH-C1-2-alkyl, C1-2-alkyl-NHCO-C1-4-alkyl-, azido, azido-C1-4-alkyl and -NO2, or c) when the ring system contains nitrogen atoms, said ring system is optionally N-substituted with 1-3 substituents selected from the group consisting of C1-4-alkyl, C1-4-alkyl-SO-, C1-4-alkyl-SO2-, C3-4-alkynyl, HO-C2-4-alkyl, C1-2-alkyl-O-C2-4- alkyl-, H2N-C2-4-alkyl, C1-2-alkyl-NH-C2-4-alkyl-, HS-C2-4-alkyl, C1-2-alkyl-S-C2-4-alkyl-, NC-C1-4-alkyl, HOOC-C1-4-alkyl, C1-2-alkyl-OCO-C1-4-alkyl-, H2NCO-C1-4-alkyl, C1-2-alkyl-NHCO-C1-4-alkyl- and azido-C2-4-alkyl; wherein when –OH, -NH2 or -SH substituents are present on the ring system they are not vicinal to a single or double carbon-heteroatom bond; G is selected from the group consisting of O and S; R is selected from the group consisting of hydrogen, fluorine and C1-4-alkyl groups R and R are independently selected from the group consisting of hydrogen and C1-4-alkyl groups, R is independently selected from the group consisting of hydrogen and methyl each one of A, A, A and A independently represents any one of N and CR, wherein the ring comprising A, A, A and A is aromatic, R is selected from the group consisting of hydrogen, halogen atoms, C 1-4-alkyl, C1-4-alkoxy, C1-4-alkyl-NH-, C1-4-alkyl-S-, C1-4-alkyl-SO-, C1-4-alkyl-SO2-, C2-4-alkynyl, C3-4-alkynyl-O-, C3-4-alkynyl-NH-, C3-4-alkynyl-S-, -OH, HO-C1-4-alkyl, C1-2-alkyl-O-C1-4-alkyl-, -NH2, H2N-C1-4-alkyl, C1-2-alkyl-NH-C1-4-alkyl-, -SH, HS-C1-4-alkyl, C1-2-alkyl-S-C1-4-alkyl-, -CN, NC-C1-4-alkyl, -COOH, HOOC-C1- 4-alkyl, -COO-C1-2-alkyl, C1-2-alkyl-OCO-C1-4-alkyl-, -CONH2, H2NCO-C1-4-alkyl, -CONH-C1-2-alkyl, C1-2-alkyl-NHCO-C1-4-alkyl-, azido, azido-C1-4-alkyl and -NO2, and pharmaceutically acceptable salts thereof for use in the treatment and/or prevention of hyperproliferative disorders.
2. The compound for use according to claim 1 wherein R is selected from the group consisting of hydrogen and C 1-4-alkyl groups.
3. The compound for use according to any one of claims 1 to 2 wherein G is an optionally substituted monocyclic, bicyclic or tricyclic heteroaromatic ring system.
4. The compound for use according to any one of claims 1 to 3 wherein the five-membered ring of G which is attached to the (CH2)n group contains 1 or 2 heteroatoms selected from N, S and O.
5. The compound for use according to any one of claims 1 to 3 wherein G is selected from the group consisting of 1H-indol-3-yl, imidazo[2,1-b]thiazol-6-yl, imidazo[1,2-a]pyridin-2-yl, 1H-indol-2-yl, benzo[d]oxazol-2-yl, imidazo[2,1-b]thiazol-3-yl, benzo[b]thiophen-2-yl, thiophen-2-yl, benzo[b]furan-2-yl, 1H-imidazol-4-yl, all of which may be optionally substituted as defined in claim 1.
6. The compound for use according to any one of claims 1 to 5 wherein G is S.
7. The compound for use according to any one of claims 1 to 6 wherein Ris selected from hydrogen atom and methyl and Rand Rare independently selected from hydrogen atom and methyl.
8. The compound for use according to any one of claims 1 to 7 wherein A, A and A are CR.
9. The compound for use according to claim 1 wherein the compound is one of: 2-imidazo[2,1-b]thiazol-6-yl-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(benzo[d]oxazol-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[5-methyl-4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(2-methyl-1H-indol-3-yl)oxazol-2-yl]acetamide 2-(5-methoxy-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(1H-indol-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(6-fluoroimidazo[1,2-a]pyridin-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(2-methylimidazo[2,1-b]thiazol-6-yl)acetamide N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(3-methylimidazo[2,1-b]thiazol-6-yl)acetamide 2-(1-methyl-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(5-fluoro-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 3-(1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]propanamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-methyl-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]propanamide 2-(6-chloro-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2- yl]acetamide 2-(1H-imidazol-4-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(benzofuran-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(4-bromothiophen-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(3-methylbenzo[b]thiophen-2- yl)acetamide 2-(5-hydroxy-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(4-bromo-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(5-nitro-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(5-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(5-methoxy-2-methyl-1H-indol-3- yl)thiazol-2-yl]acetamide N-[4-(6-fluoro-2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(2-methyl-5-nitro-1H-indol-3-yl)thiazol-2-yl]acetamide 30 N-[4-(5-amino-2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide N-[5-fluoro-4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide and pharmaceutically acceptable salts thereof.
10. The compound for use according to any one of claims 1 to 9 wherein the disease is cancer.
11. A compound of formula (I’) CN G N OR R (CH)n RGCCNHC AAAA R (I’) wherein n is 0 or 1; G is an heteroaromatic ring system selected from the group consisting of benzo[d]oxazolyl, imidazo[1,2-a]pyridinyl, benzo[b]thiophenyl, benzo[d]imidazo[2,1-b]thiazolyl, 1H-imidazol-4-yl, indol-2-yl and benzofuran-2-yl and is said ring system is: a) unsubstituted, b) C-substituted with 1-3 substituents selected from the group consisting of halogen atoms, C1-4-alkyl, C1-4-alkoxy, C1-4-alkyl-NH-, C1-4-alkyl-S-, C1-4-alkyl-SO-, C1-4-alkyl-SO2-, C2-4-alkynyl, C3-4-alkynyl-O-, C3-4-alkynyl-NH-, C3-4-alkynyl-S-, -OH, HO-C1-4-alkyl, C1-2-alkyl-O-C1-4-alkyl-, -NH2, H2N-C1-4-alkyl, C1-2-alkyl-NH-C1-4-alkyl-, -SH, HS-C1-4-alkyl, C1-2-alkyl-S-C1-4-alkyl-, -CN, NC- C1-4-alkyl, -COOH, HOOC-C1-4-alkyl, -COO-C1-2-alkyl, C1-2-alkyl-OCO-C1-4-alkyl-, -CONH2, H2NCO-C1-4-alkyl, -CONH-C1-2-alkyl, C1-2-alkyl-NHCO-C1-4-alkyl-, azido, azido-C1-4-alkyl and -NO2; c) when the ring system contains nitrogen atoms, said ring system is optionally N-substituted with 1 substituent selected from the group consisting of C1-4-alkyl, C1-4-alkyl-SO-, C1-4-alkyl-SO2-, C3-4-alkynyl, HO-C2-4-alkyl, C1-2-alkyl-O-C2-4-alkyl-, H2N-C2-4-alkyl, C1-2-alkyl-NH-C2-4-alkyl-, HS-C2-4-alkyl, C1-2-alkyl-S-C2-4-alkyl-, NC-C1-4-alkyl, HOOC-C1-4-alkyl, C1-2-alkyl-OCO-C1-4-alkyl-, H2NCO- C1-4-alkyl, C1-2-alkyl-NHCO-C1-4-alkyl- and azido-C2-4-alkyl; wherein when –OH, -NH2 or -SH substituents are present on the ring system they are not vicinal to a single or double carbon-heteroatom bond; G is selected from the group consisting of O and S; R is selected from the group consisting of hydrogen, fluorine and C1-4 alkyl groups R and R are independently selected from the group consisting of hydrogen and C1-4 alkyl groups, R is independently selected from the group consisting of hydrogen and methyl each one of A, A, A and A independently represents any one of N and CR, wherein the ring comprising A, A, A and A is aromatic, R is selected from the group consisting of hydrogen, halogen atoms, C 1-4-alkyl, C1-4-alkoxy, C1-4-alkyl-NH-, C1-4-alkyl-S-, C1-4-alkyl-SO-, C1-4-alkyl-SO2-, C2-4-alkynyl, C3-4-alkynyl-O-, C3-4-alkynyl-NH-, C3-4-alkynyl-S-, -OH, HO-C1-4-alkyl, C1-2-alkyl-O-C1-4-alkyl-, -NH2, H2N-C1-4-alkyl, C1-2-alkyl-NH-C1-4-alkyl-, -SH, HS-C1-4-alkyl, C1-2-alkyl-S-C1-4-alkyl-, -CN, NC-C1-4-alkyl, -COOH, HOOC-C1-4-alkyl, -COO-C1-2-alkyl, C1-2-alkyl-OCO-C1-4-alkyl-, -CONH2, H2NCO-C1-4-alkyl, -CONH-C1-2-alkyl, C1-2-alkyl-NHCO-C1-4-alkyl-, azido, azido-C1-4-alkyl and -NO2, and pharmaceutically acceptable salts thereof.
12. The compound according to claim 11 wherein R is selected from the group consisting of hydrogen and C1-4 alkyl groups.
13. Compound according to any one claims 11 to 12 wherein G is S.
14. The compound according to any one of claims 11 to 13 wherein Ris selected from hydrogen atom and methyl and Rand Rare independently selected from hydrogen atom and methyl.
15. The compound according to any one of claims 11 to 14 wherein A, A and A are CR.
16. The compound according to claim 11 which is one of: 2-imidazo[2,1-b]thiazol-6-yl-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(benzo[d]oxazol-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[5-methyl-4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(2-methyl-1H-indol-3-yl)oxazol-2-yl]acetamide 2-(5-methoxy-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(1H-indol-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(6-fluoroimidazo[1,2-a]pyridin-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(2-methylimidazo[2,1-b]thiazol-6-yl)acetamide N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(3-methylimidazo[2,1-b]thiazol-6- yl)acetamide 2-(1-methyl-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(5-fluoro-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 3-(1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]propanamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-methyl-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]propanamide 2-(6-chloro-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(1H-imidazol-4-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(benzofuran-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(4-bromothiophen-2-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(3-methylbenzo[b]thiophen-2-yl)acetamide 2-(5-hydroxy-1H-indol-3-yl)-N-[4-(2-methyl-1H-indol-3-yl)thiazol-2- yl]acetamide N-[4-(4-bromo-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(5-nitro-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(5-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(5-methoxy-2-methyl-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(6-fluoro-2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6- yl)acetamide 2-(imidazo[2,1-b]thiazol-6-yl)-N-[4-(2-methyl-5-nitro-1H-indol-3-yl)thiazol-2-yl]acetamide N-[4-(5-amino-2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide N-[5-fluoro-4-(2-methyl-1H-indol-3-yl)thiazol-2-yl]-2-(imidazo[2,1-b]thiazol-6-yl)acetamide and pharmaceutically acceptable salts thereof.
17. A pharmaceutical composition comprising a compound as defined in any one of claims 11 to 16 and at least one pharmaceutically acceptable excipient.
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| Application Number | Priority Date | Filing Date | Title |
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| EP21382343.8A EP4079304A1 (en) | 2021-04-21 | 2021-04-21 | Compounds for use in the treatment of hyperproliferative disorders |
| PCT/EP2022/060579 WO2022223704A1 (en) | 2021-04-21 | 2022-04-21 | Compounds for use in the treatment of hyperproliferative disorders |
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| IL307868A true IL307868A (en) | 2023-12-01 |
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| IL307868A IL307868A (en) | 2021-04-21 | 2022-04-21 | Compounds for use in the treatment of hyperproliferative disorders |
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| US (1) | US20240208998A1 (en) |
| EP (2) | EP4079304A1 (en) |
| JP (1) | JP2024515705A (en) |
| KR (1) | KR20240013112A (en) |
| CN (1) | CN117320715A (en) |
| AU (1) | AU2022260529A1 (en) |
| BR (1) | BR112023021959A2 (en) |
| CA (1) | CA3216090A1 (en) |
| IL (1) | IL307868A (en) |
| MX (1) | MX2023012457A (en) |
| WO (1) | WO2022223704A1 (en) |
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| ES2609912T3 (en) * | 2007-06-22 | 2017-04-25 | Hydra Biosciences, Inc. | Compounds of 2,6-dioxo, -2,3-dihydro-1h-purine useful for the treatment of disorders related to the activity of the trpa1 channel |
-
2021
- 2021-04-21 EP EP21382343.8A patent/EP4079304A1/en not_active Withdrawn
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2022
- 2022-04-21 CN CN202280035450.7A patent/CN117320715A/en active Pending
- 2022-04-21 BR BR112023021959A patent/BR112023021959A2/en unknown
- 2022-04-21 US US18/556,456 patent/US20240208998A1/en active Pending
- 2022-04-21 EP EP22723682.5A patent/EP4326262A1/en active Pending
- 2022-04-21 JP JP2023564537A patent/JP2024515705A/en active Pending
- 2022-04-21 KR KR1020237040063A patent/KR20240013112A/en active Pending
- 2022-04-21 WO PCT/EP2022/060579 patent/WO2022223704A1/en not_active Ceased
- 2022-04-21 IL IL307868A patent/IL307868A/en unknown
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- 2022-04-21 AU AU2022260529A patent/AU2022260529A1/en active Pending
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| JP2024515705A (en) | 2024-04-10 |
| WO2022223704A1 (en) | 2022-10-27 |
| MX2023012457A (en) | 2023-11-22 |
| EP4079304A1 (en) | 2022-10-26 |
| CA3216090A1 (en) | 2022-10-27 |
| KR20240013112A (en) | 2024-01-30 |
| AU2022260529A1 (en) | 2023-11-09 |
| US20240208998A1 (en) | 2024-06-27 |
| BR112023021959A2 (en) | 2023-12-26 |
| CN117320715A (en) | 2023-12-29 |
| EP4326262A1 (en) | 2024-02-28 |
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