Patents Assigned to Spirogen Limited
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Publication number: 20110256157Abstract: Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.Type: ApplicationFiled: April 15, 2011Publication date: October 20, 2011Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, Luke Masterson, Arnaud Tiberghien, John A. Flygare, Janet L. Gunzner, Paul Polakis, Andrew Polson, Helga E. Raab, Susan D. Spencer
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Publication number: 20110201803Abstract: The invention relates to certain pyrrolobenzodiazepines (PBDs), and in particular pyrrolobenzodiazepine dimers bearing C2 substitutions, including compounds of formula (T): wherein: R2 is CHR2A, and R2A is independently selected from H, R, CO2R, COR, CHO, CO2H, and halo; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R8 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, NO2, Me3Sn and halo; R is independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; or the compound is a dimer with each monomer being of formula (M), where the R7 groups or R8 groups of each monomer form together a dimer bridge having the formula —X—R?—X— linking the monomers; wherein R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), and/or aromatic rings, e.g.Type: ApplicationFiled: October 16, 2009Publication date: August 18, 2011Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, Stephen John Gregson, Zhizhi Chen, Arnaud Charles Tiberghien, Luke Masterson
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Publication number: 20110196148Abstract: Claimed are unsymmetrical Pyrrolobenzodiazepine-dimers (PBD-dimers) of formula (I), that are unsymmetrical due at least to the values that the variables R12 and R2 represent. Formula (I), wherein: R2 is of formula (II), where A is a C5-7 aryl group, X is selected from the group comprising: OH, SH, CO2H, COH, N?C?O, NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl, and (OC2H4)mOCH3, where m is 1 to 3, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)m—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is —CH?CH—, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene. The other variables are as defined in the claims. The compounds are useful for the treatment of proliferative diseases.Type: ApplicationFiled: October 16, 2009Publication date: August 11, 2011Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, Stephen John Gregson, Luke Masterson
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Publication number: 20110162227Abstract: Methods of preparing ZC-423 (I) which result in varying enantiomeric ratios.Type: ApplicationFiled: July 22, 2009Publication date: July 7, 2011Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, Stephen John Gregson, Zhizhi Chen, Arnaud Charles Tiberghien, Luke Masterson
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Publication number: 20110160192Abstract: Compounds of formula (I): Z?-CO-A-B—NH-Z (I) wherein: Z is H or an amino protecting group; Z? is OH, a protected or activated hydroxyl group or Cl; A is an optionally substituted C5-6 arylene group; and B is an optionally substituted C5-6 arylene group.Type: ApplicationFiled: March 7, 2011Publication date: June 30, 2011Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, Geoffrey Wells
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Patent number: 7741319Abstract: The present inventors have developed a key intermediate for the production of C2 substituted PBDs, which has a leaving group at the C2 position, a carbamate protecting group at the N10 position and a protected hydroxy group at the C11 position. In a first aspect, the present invention comprises a compound with a the formula (I), wherein: R10 is a carbamate-based nitrogen protecting group; R11 is an oxygen protecting group; and R2 is a labile leaving group. In a further aspect, the present invention comprises a method of synthesising a compound of formula (III), or a solvate thereof, from a compound of formula (I) as defined in the first aspect, R16 is either O—R11, wherein R11 is as defined in the first aspect, or OH, or R10 and R16 together form a double bond between N10 and C11; and R15 is R. The other substituents are defined in the claims.Type: GrantFiled: March 1, 2005Date of Patent: June 22, 2010Assignee: Spirogen LimitedInventors: Philip Wilson Howard, Stephen John Gregson
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Publication number: 20100113425Abstract: Compounds of the formula I: or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo; R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2?, R6?, R7?, R9?, X? and M? are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M? may together represent a divalent pharmaceutically acceptable cation.Type: ApplicationFiled: November 2, 2009Publication date: May 6, 2010Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, Zhizhi Chen, Stephen John Gregson
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Patent number: 7704924Abstract: A compound of formula (IV): O is a solid support; L is a linking group or a single bond; X? is selected from CO, NH, S, or O; A is O, S, NH, or a single bond; R2 and R3 are independently selected from: H, R, OH, OR, ?O, ?CH—R, ?CH2, CH2—CO2R, CH2—CO2H, CH2—SO2R, O—SO2R, CO2R, COR, CN and there is optionally a double bond between C1 and C2 or C2 and C3; R6, R7, and R9 are independently selected from H, R, OH, OR, halo, nitro, amino, Me3Sn; R11 is either H or R; Q is S, O or NH; R10 is a nitrogen protecting group; and Y is a divalent group such that HY?R, and other related compounds and collections of compounds.Type: GrantFiled: June 24, 2003Date of Patent: April 27, 2010Assignee: Spirogen LimitedInventors: David Edwin Thurston, Philip Wilson Howard
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Patent number: 7612062Abstract: Compounds of the formula: (I) or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo; R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2?, R6?, R7?, R9?, X? and M? are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M? may together represent a divalent pharmaceutically acceptable cation.Type: GrantFiled: April 21, 2006Date of Patent: November 3, 2009Assignee: Spirogen LimitedInventors: Stephen John Gregson, Philip Wilson Howard, Zhizhi Chen
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Patent number: 7557099Abstract: Compounds and a method of synthesis of compounds of formula (Ia) or (Ib): and salts, solvates, and chemically protected forms thereof, wherein the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 and R3 are independently selected from —H, ?O, ?CH2, —CN, —R, OR, halo, ?CH—R, O—SO2—R, CO2R and COR; R10 is a carbamate-based nitrogen protecting group; and R11 is an oxygen protecting group.Type: GrantFiled: March 1, 2005Date of Patent: July 7, 2009Assignee: Spirogen LimitedInventors: Philip Wilson Howard, Gyoung-Dong Kang
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Patent number: 7528126Abstract: A compound of formula (I) and salts and solvates thereof, wherein: R10 is a nitrogen protecting group and R11 is either OH or O—R12, wherein R12 is an oxygen protecting group, or R10 and R11 together form a double bond between N10 and C11; and R10? and R11? are selected from the same options as R10 and R11 respectively.Type: GrantFiled: March 9, 2005Date of Patent: May 5, 2009Assignee: Spirogen LimitedInventors: Philip Wilson Howard, Stephen John Gregson, Peter William Taylor, David Edwin Thurston, Tsveta Stefanova Hadjivassileva
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Patent number: 7429658Abstract: A method of synthesis of a N-10 protected PBD compound of formula (I): via an intermediate of formula (II) or formula (V):Type: GrantFiled: September 10, 2004Date of Patent: September 30, 2008Assignee: Spirogen LimitedInventors: Philip Howard, Luke Masterson
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Publication number: 20080214525Abstract: A compound of formula (I); or a salt or solvate thereof, wherein: the dotted line indicates the optional presence of a double bond between C2 and C3; R2 is selected from —H, —OH, =0, ?CH2, —CN, —R, OR, halo, ?CH—R, O—SO2—R, CO2R and COR; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo, where R and R? are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R10 and R11 either together form a double bond, or are selected from H and YRY, where Y is selected from O, S and NH and R is H or C1-7 alkyl or H and SOxM, where x is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; each X is independently a heteroarylene group; n is from 1 to 6; and RE is C1-4 alkyl. The compound is useful for the treatment of proliferative diseases.Type: ApplicationFiled: October 5, 2006Publication date: September 4, 2008Applicant: SPIROGEN LIMITEDInventors: Philip Wilson Howard, David Edwin Thurston, Geoffrey Wells
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Patent number: 7407951Abstract: Compounds of formula (I): formula (I) and salts, solvates, chemically protected forms, and prodrugs thereof, are disclosed wherein R2 is selected from: an optionally substituted napthyl group; an optionally substituted thiophenyl or furanyl group; and a phenyl group substituted by: one or more chloro or fluoro groups; an ethyl or propyl group; a 4-t-butyl group; a 2-methyl group; or two methyl groups in the 2- and 6-positions.Type: GrantFiled: November 14, 2003Date of Patent: August 5, 2008Assignee: Spirogen LimitedInventors: David Edwin Thurston, Philip Wilson Howard
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Publication number: 20080167293Abstract: Compounds of the formula: (I) or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR?, nitro, Me3Sn and halo; R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2?, R6?, R7?, R9?, X? and M? are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M? may together represent a divalent pharmaceutically acceptable cation.Type: ApplicationFiled: April 21, 2006Publication date: July 10, 2008Applicant: Spirogen LimitedInventors: Philip Wilson Howard, Zhizhi Chen, Stephen John Gregson
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Publication number: 20080090812Abstract: A pyrrolobenzodiazepine dimer compound of Formula (I): or pharmaceutically acceptable salt or solvate thereof is useful as a therapeutic agent for the treatment of leukaemias, especially B-cell leukaemias, that exhibit resistance to other chemotherapeutic drugs, wherein: the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 and R3 are independently selected from —H, ?O, ?CH2, —CN, —R, OR, halo, ?CH—R, O—SO2—R, CO2R and COR; R6, R7 and R9 are independently selected from II, R, OII, OR, SII, SR, NII2, NIIR, NRR?, nitro, Me3Sn and halo; where R and R? are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R10 is a carbamate-based nitrogen protecting group and R15 is either O—R11, wherein R is an oxygen protecting group, or OH, or R10 and R15 together form a double bond between N10 and C11; R? is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings, and each X isType: ApplicationFiled: May 5, 2005Publication date: April 17, 2008Applicant: SPIROGEN LIMITEDInventors: Christopher John Pepper, David Edwid Thurston
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Publication number: 20070249591Abstract: Compounds of formula (1): Z?-CO-A-B—NH-Z (I) wherein: Z is H or an amino protecting group; Z? is OH, a protected or activated hydroxyl group or Cl; A is an optionally substituted C5-6 arylene group; and B is an optionally substituted C5-6 arylene group.Type: ApplicationFiled: March 1, 2005Publication date: October 25, 2007Applicant: Spirogen LimitedInventors: Philip Howard, Geoffrey Wells
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Patent number: 7265105Abstract: A compound of the formula II: wherein: R?2 is CHR?2, where R?2 is H. R6 and R9 are H and R7 is OMe and the compound is a dimer with each monomer being the same and being of formula II, where the R8 groups of the monomers form together a bridge having the formula —O—(CH2)p—O—, where p is 5, linking the monomers.Type: GrantFiled: March 2, 2006Date of Patent: September 4, 2007Assignee: Spirogen LimitedInventors: David Edwin Thurston, Philip Wilson Howard
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Publication number: 20070191309Abstract: Compounds and a method of synthesis of compounds of formula (Ia) or (Ib): and salts, solvates, and chemically protected forms thereof, wherein the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 and R3 are independently selected from —H, ?O, ?CH2, —CN, —R, OR, halo, ?CH—R, O—SO2—R, CO2R and COR; R10 is a carbamate-based nitrogen protecting group; and R11 is an oxygen protecting group.Type: ApplicationFiled: March 1, 2005Publication date: August 16, 2007Applicant: Spirogen LimitedInventors: Philip Howard, Gyoung-Dong Kang
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Publication number: 20070191349Abstract: Compounds of formula (I): PBD-A-Y—X—(Het)na-L-(Het)nb-L-(Het)nc-T-(Het?)nd-L-(Het?)ne-L-(Het?)nf—X?—Y?- A?-PBD? and salts, solvates and chemically protected forms thereof, are disclosed wherein the PBD units have the formulae (PBD) (PBD?) with the bonds at the 8 position on each molecule bond to the A and A? groups respectively; A is selected from O, S, NH or a single bond, and each Het and Het? is respectively an amino-heteroarylene-carbonyl group; X and X? are both either NH or C (?O)-Q—C(?O)— wherein Q is a divalent group such that HY?R; in a second aspectm the invention comprises compounds of the general formula (II): PBD-A-Y—X—(Het)ng-[L-(Het)nh]nj-X?—Y?-A?-PBD?. Wherein: PBD and PBD? are as defined above, X and X? are either NH and C(?O) respectively or C(O) and NH respectively; the other substitutents are defined in the claims. Further aspects of the present invention relate to their use in the manufacture of a medicament for the treatment of a proliferative disease.Type: ApplicationFiled: March 1, 2005Publication date: August 16, 2007Applicant: SPIROGEN LIMITEDInventors: Philip Howard, Stephen Gregson, Arnaud Tiberghien