CY1114846T1 - BENZIMIDAZOLE PRODUCERS AND THEIR USE OF PROTEIN KINASES - Google Patents

BENZIMIDAZOLE PRODUCERS AND THEIR USE OF PROTEIN KINASES

Info

Publication number
CY1114846T1
CY1114846T1 CY20141100070T CY141100070T CY1114846T1 CY 1114846 T1 CY1114846 T1 CY 1114846T1 CY 20141100070 T CY20141100070 T CY 20141100070T CY 141100070 T CY141100070 T CY 141100070T CY 1114846 T1 CY1114846 T1 CY 1114846T1
Authority
CY
Cyprus
Prior art keywords
group
hydrogen
optionally substituted
carbocyclic
hydrocarbyl
Prior art date
Application number
CY20141100070T
Other languages
Greek (el)
Inventor
Valerio Berdini
Michael Alistair O'brien
Maria Grazia Carr
Theresa Rachel Early
Eva Figueroa Navarro
Adrian Liam Gill
Steven Howard
Gary Trewartha
Alison Jo-Anne Woolford
Andrew James Woodhead
Paul Wyatt
Original Assignee
Astex Therapeutics Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB0315657.7A external-priority patent/GB0315657D0/en
Priority claimed from GB0324919A external-priority patent/GB0324919D0/en
Priority claimed from EP04743172.1A external-priority patent/EP1648426B1/en
Application filed by Astex Therapeutics Limited filed Critical Astex Therapeutics Limited
Publication of CY1114846T1 publication Critical patent/CY1114846T1/en

Links

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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

Η εφεύρεση παρέχει ενώσεις που έχουν δραστικότητα σαν καταστολείς των κινασών (kinases) που εξαρτώνται από την κυκλίνη (cyclin), κινασών (kinases)-3 συνθάσης (synthase) γλυκογόνου και κινασών (kinases) Aurora, για χρήση στην θεραπεία καταστάσεων ασθενειών και παθήσεων όπως ο καρκίνος με την μεσολάβηση κινασών (kinases). Οι συνθέσεις έχουν τον γενικό τύπο (I), όπου το Χ είναι CR5 ή Ν, το Α είναι ένας δεσμός ή -(CH2)m-(B)n-, το Β είναι C=O, NRg(C=O) ή O(C=O), το Rg είναι υδρογόνο ή C1-4 υδροκαρβύλιο προαιρετικά αντικατεστημένο με hydroxy ή C1-4 alcoxy, το m είναι 0, 1 ή 2, το n είναι 0 ή 1, το R0 είναι υδρογόνο ή, μαζί με το NRg όταν υπάρχει, σχηματίζει μία καρβοκυκλική ομάδα -(CH2)P- όπου το 1p είναι 2 μέχρι 4, το R1 είναι υδρογόνο, μία καρβοκυκλική ομάδα ή έτερο-κυκλική ομάδα που έχει από 3 μέχρι 12 μέλη δακτυλίου, ή μία προαιρετικά αντικατεστημένη ομάδα C1-8 υδροκαρβυλίου, το R2 είναι υδρογόνο, αλογόνο, methoxy, ή μία ομάδα C1-4 υδροκαρβυλίου, προαιρετικά αντικατεστημένη με αλογόνο, υδροξύλιο ή methoxy, τα R3 και R4, μαζί με τα άτομα του άνθρακα στα οποία είναι προσαρτημένα σχηματίζουν ένα προαιρετικά αντικατεστημένο συγχωνευμένο καρβοκυκλικό ή έτερο-κυκλικό δακτύλιο που έχει από 5 μέχρι 7 μέλη δακτυλίου από τα οποία 3 μπορεί να είναι έτερο-άτομα που επιλέγονται από Ν, Ο και S, το R5 είναι υδρογόνο, μία ομάδα R2 ή μία ομάδα R10, όπου το R10 επιλέγεται από αλογόνο, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, mono- ή di-hydrocarbylamino C1-4, από καρβοκυκλικές ή έτερο-κυκλικές ομάδες που έχουν από 3 μέχρι 12 μέλη δακτυλίου, μία ομάδα Ra-Rb, όπου το Ra είναι ένας δεσμός, Ο, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRC, SO2NRc ή NRcSO2 και το Rb επιλέγεται από υδρογόνο, από καρβοκυκλικές και έτερο-κυκλικές ομάδες που έχουν από 3 μέχρι 12 μέλη δακτυλίου, και μία ομάδα C1-8 υδροκαρβυλίου προαιρετικά αντικατεστημένη με ένα ή περισσότερους παράγοντες αντικατάστασης που επιλέγονται από hydroxy, oxo, αλογόνο, cyano, nitro, carboxy, amino, mono- ή di-hydrocarbylamino C1-4, καρβοκυκλικές και έτερο-κυκλικές ομάδες που έχουν από 3 μέχρι 12 μέλη δακτυλίου, όπου ένα ή περισσότερα άτομα άνθρακα της ομάδας C1-8 υδροκαρβυλίου μπορεί να είναι προαιρετικά αντικατεστημένα με Ο, S, SO, SO2, NRC, Χ1C(Χ2), C(X2)X1 or X1C(X2)X1, το Rc επιλέγεται από υδρογόνο και C1-4 υδροκαρβύλιο και το Χ1 είναι Ο, S ή NRC και το Χ2 είναι =O, =S ή =NRC. Επίσης περιλαμβάνονται στον τύπο (I) τα άλατα, οι ενώσεις διαλύτη με διαλυμένη ουσία και τα Ν-οξείδια των ενώσεων.The invention provides compounds having activity as suppressors of cyclin dependent kinases, glycogen synthase kinases -3 and Aurora kinases for use in the treatment of disease states and conditions such as kinase mediated cancer. The compositions have the general formula (I), wherein X is CR5 or N, A is a bond or - (CH2) m- (B) n-, B is C = O, NRg (C = O) or O (C = O), Rg is hydrogen or C1-4 hydrocarbyl optionally substituted with hydroxy or C1-4 alcoxy, m is 0, 1 or 2, n is 0 or 1, R0 is hydrogen or, together with NRg, when present, forms a carbocyclic group - (CH2) P- wherein 1p is 2 to 4, R1 is hydrogen, a carbocyclic or heterocyclic group having from 3 to 12 ring members, or an optionally substituted group C1-8 hydrocarbyl, R2 is hydrogen, halogen, methoxy, or a group C1-4 Hydrocarbyl, optionally substituted with halogen, hydroxyl or methoxy, R3 and R4, together with the carbon atoms to which they are attached, form an optionally substituted fused carbocyclic or heterocyclic ring having from 5 to 7 ring members which 3 may be hetero-atoms selected from N, O and S, R5 is hydrogen, a group R2 or a group R10, wherein R10 is selected from halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, mono - or di-hydrocarbylamino C1-4, from carbocyclic or heterocyclic groups having from 3 to 12 m ring members, a group of Ra-Rb, wherein Ra is a bond, O, CO, X1C (X2), C (X2) X1, X1C (X2) X1, S, SO, SO2, NRC, SO2NRc or NRcSO2 and Rb is selected from hydrogen, from carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C1-8 hydrocarbyl group optionally substituted with one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, carboxy , amino, mono- or di-hydrocarbylamino C1-4, carbocyclic and heterocyclic groups having from 3 to 12 ring members, wherein one or more carbon atoms of the C1-8 hydrocarbyl group may are optionally substituted with O, S, SO, SO2, NRC, X1C (X2), C (X2) X1 or X1C (X2) X1, Rc is selected from hydrogen and C1-4 hydrocarbyl and X1 is O, S or NRC and X2 are = O, = S or = NRC. Also included in formula (I) are the salts, the solvent-soluble compounds and the N-oxides of the compounds.

CY20141100070T 2003-07-03 2014-01-28 BENZIMIDAZOLE PRODUCERS AND THEIR USE OF PROTEIN KINASES CY1114846T1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US48468503P 2003-07-03 2003-07-03
GBGB0315657.7A GB0315657D0 (en) 2003-07-03 2003-07-03 Pharmaceutical compounds
US51437403P 2003-10-24 2003-10-24
GB0324919A GB0324919D0 (en) 2003-10-24 2003-10-24 Pharmaceutical compounds
EP04743172.1A EP1648426B1 (en) 2003-07-03 2004-07-05 Benzimidazole derivatives and their use as protein kinases inhibitors

Publications (1)

Publication Number Publication Date
CY1114846T1 true CY1114846T1 (en) 2016-12-14

Family

ID=33568694

Family Applications (2)

Application Number Title Priority Date Filing Date
CY20141100070T CY1114846T1 (en) 2003-07-03 2014-01-28 BENZIMIDAZOLE PRODUCERS AND THEIR USE OF PROTEIN KINASES
CY20141100311T CY1115093T1 (en) 2003-07-03 2014-04-28 BENZIMIDAZOLE PRODUCERS AND THEIR USE OF PROTEIN KINASES

Family Applications After (1)

Application Number Title Priority Date Filing Date
CY20141100311T CY1115093T1 (en) 2003-07-03 2014-04-28 BENZIMIDAZOLE PRODUCERS AND THEIR USE OF PROTEIN KINASES

Country Status (4)

Country Link
KR (1) KR101190964B1 (en)
CY (2) CY1114846T1 (en)
HK (1) HK1087925A1 (en)
IL (1) IL172840A (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA04003954A (en) * 2001-10-26 2004-11-29 Aventis Pharma Inc Benzimidazoles and analogues and their use as protein kinases inhibitors.

Also Published As

Publication number Publication date
KR20060082847A (en) 2006-07-19
IL172840A (en) 2014-07-31
KR101190964B1 (en) 2012-10-12
HK1087925A1 (en) 2006-10-27
IL172840A0 (en) 2006-06-11
CY1115093T1 (en) 2016-12-14

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