Nitrogen Of The Hetero Ring Is Shared By An Additional Cyclo Of The Tricyclo Ring System Patents (Class 540/496)
  • Patent number: 11466032
    Abstract: The invention relates to a compound of formula (I) or formula (II) or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; which are useful as medicaments, in particular as anti-proliferative agents and for use as a drug in an antibody-drug conjugate and in the treatment of proliferative diseases.
    Type: Grant
    Filed: September 4, 2018
    Date of Patent: October 11, 2022
    Inventors: Paul Joseph Mark Jackson, David Edwin Thurston, Khondaker Mirazur Rahman
  • Patent number: 9056914
    Abstract: Provided herein are compounds of formula (I):
    Type: Grant
    Filed: January 25, 2013
    Date of Patent: June 16, 2015
    Assignee: SANOFI
    Inventors: Alain Commercon, Laurence Gauzy-Lazo, Philippe Hubert
  • Publication number: 20150133435
    Abstract: Pyrrolobenzodiazepine (PBDs) having a (1-methyl-1H-pyrrol-3-yl)phenyl based amino residue were found to be highly effective compounds having improved cytotoxicity ad DNA binding properties.
    Type: Application
    Filed: April 30, 2013
    Publication date: May 14, 2015
    Inventors: Philip Wilson Howard, David Edwin Thurston, Khondaker Mirazur Rahman
  • Publication number: 20150126495
    Abstract: A compound of formula (I) or a salt or solvate thereof, wherein the dotted double bond indicates the presence of a single or double bond between C2 and C3; R2 is selected from —H, —OH, ?O, ?CH2, —CN, —R, OR, halo, dihalo, ?CHR, ?CHRR?, —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 QRQ respectively, where Q is selected from O, S and NH and RQ is H or C1-7 alkyl or H and SOxM, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation; A is selected from (A1), (A2), (A3), (A4) or (A5) where X1 and Y1 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively; X2 and Y2 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively; Z1 is selected fr
    Type: Application
    Filed: April 30, 2013
    Publication date: May 7, 2015
    Inventors: Philip Wilson Howard, David Edwin Thurston, Khondaker Mirazur Rahman, Peter William Taylor
  • Publication number: 20150031652
    Abstract: Disclosed are compounds of the following formula: in which R1, R2, R3, R4, R5, R6, R7, X, and t are defined in the specification. Also disclosed are pharmaceutical compositions, kits, and articles of manufacture, which contain the compounds, methods and intermediates useful for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions related to PARP activity.
    Type: Application
    Filed: August 1, 2014
    Publication date: January 29, 2015
    Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED
    Inventors: Anthony R. Gangloff, Andrew John Jennings, Benjamin Jones, Andre A. Kiryanov
  • Patent number: 8895727
    Abstract: Disclosed is the synthesis of [18F]flumazenil that is useful in imaging epileptic lesions by PET (positron emission tomography). A method for preparing [18F]flumazenil by reacting a diaryliodonium salt precursor with the positron-emitting radionuclide fluorine-18. [18F]flumazenil can be prepared from the diaryliodonium salt precursor in the presence of kryptofix2.2.2./potassium carbonate(K2.2.2./K2CO3) and TEMPO in dimethylformamide (DMF) at a high yield.
    Type: Grant
    Filed: November 22, 2013
    Date of Patent: November 25, 2014
    Assignee: Bio Imaging Korea Co., Ltd.
    Inventors: Byung Chul Lee, Byung Seok Moon, Ji Sun Kim
  • Publication number: 20140302066
    Abstract: This invention relates to pyrrolobenzodiazepines (PBDs), in particular pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position in each monomer unit, and their inclusion in targeted conjugates. The differing substituent groups may offer advantages in the preparation and use of the compounds, particularly in their biological properties and the synthesis of conjugates, and the biological properties of these conjugates.
    Type: Application
    Filed: October 12, 2012
    Publication date: October 9, 2014
    Inventors: Scott Jeffrey, Patrick Burke, Philip Wilson Howard
  • Patent number: 8853203
    Abstract: The invention relates to compound of the formula I or a salt thereof, wherein the substituents are as defined in the specification; to its preparation, to its use as medicament and to medicaments comprising it.
    Type: Grant
    Filed: August 22, 2013
    Date of Patent: October 7, 2014
    Assignee: Novartis AG
    Inventors: Dirk Behnke, David Carcache, Peter Ertl, Manuel Koller, David Orain
  • Publication number: 20140294868
    Abstract: Conjugate compounds of formula (A): wherein: R2 is where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester or, when one of R36a and R36b is H, the other is selected from nitrile and a C1-4 alkyl ester; 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; Y is selected from formulae A1, A2, A3, A4, A5 and A6: L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; RA4 is a C1-6 alkylene group; either (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is OSOzM, where
    Type: Application
    Filed: March 13, 2014
    Publication date: October 2, 2014
    Inventors: Philip Wilson HOWARD, John A. FLYGARE, Thomas PILLOW, Binqing WEI
  • Patent number: 8846661
    Abstract: The invention relates to compounds that are diazahomoadamantane derivatives, compositions comprising such compounds, and methods of using such compounds and compositions.
    Type: Grant
    Filed: June 18, 2010
    Date of Patent: September 30, 2014
    Assignee: AbbVie Inc.
    Inventors: Michael R. Schrimpf, Kevin B. Sippy
  • Publication number: 20140286970
    Abstract: A compound, or a pharmaceutically acceptable salt or solvate thereof, or conjugates thereof, selected from the group consisting of formula wherein: (a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is S02M, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically acceptable cation.
    Type: Application
    Filed: October 12, 2012
    Publication date: September 25, 2014
    Inventors: Scott Jeffrey, Patrick Burke, Philip Wilson Howard
  • Publication number: 20140275019
    Abstract: The present invention relates to tetrahydropyridine derivatives of formula (1) which may be therapeutically useful as anti-bacterial agents, more particularly FabI inhibitors. in which X, Y, Z and “n” have the same meanings given in the specification, and pharmaceutically acceptable salts and pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage in inhibiting Enoyl-ACP reductase enzyme (FabI) activity. The present invention also provides methods for synthesizing and administering the FabI inhibitory compounds. The present invention also provides pharmaceutical formulations comprising at least one of the FabI inhibitory compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
    Type: Application
    Filed: June 3, 2014
    Publication date: September 18, 2014
    Applicants: Aurigene Discovery Technologies Limited, UM Pharmauji Sdn.BHD
    Inventors: Mohamed Takhi, Subramanya Hosahalli, Sunil Kumar Panigrahi, Muni Kumar Mahadari, Chandrashekar Reddy Kottam, Noorsaadah Abd Rahman, Rohana Yusof
  • Publication number: 20140274907
    Abstract: A compound with the formula (I), wherein: R2 is of formula (II), where X is selected from the group comprising: OH, SH, CO2H, COH, N?C?O, NHNH2, CONHNH2, formula (A), formula (B), NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl; RC1, RC2 and RC3 are independently selected from H and unsubstituted C1-2 alkyl; and either: R12 is selected from the group consisting of: (ia) 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; (ib) C1-5 saturated aliphatic alkyl; (ic) C3-6 saturated cycloalkyl; (id) formula (C), wherein each of R21, R22 and R23 are independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R12 group is no more than 5; (ie) formula (D), wherein one of R25a and R25b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group
    Type: Application
    Filed: October 12, 2012
    Publication date: September 18, 2014
    Applicant: SPIROGEN SARL
    Inventors: Philip Wilson Howard, Arnaud Tiberghien, Scott Jeffrey, Patrick Burke
  • Patent number: 8835421
    Abstract: The present invention provides a compounds of general formula (8), (11) and (14), useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of general formula (8), (11) and (14).
    Type: Grant
    Filed: October 31, 2008
    Date of Patent: September 16, 2014
    Assignee: Council of Scientific and Industrial Research
    Inventors: Ahmen Kamal, Pogula Praveen Kumar, Bobburi Naga Seshadri, Kokkonda Sreekanth
  • Patent number: 8829184
    Abstract: A compound of formula (I): which is substantially free of any of the corresponding compound of formula (IB): methods of making such compounds, and the further transformation of such compounds.
    Type: Grant
    Filed: April 15, 2011
    Date of Patent: September 9, 2014
    Assignee: Spirogen SARL
    Inventors: Philip Wilson Howard, Luke Masterson, Arnaud Tiberghien
  • Publication number: 20140234346
    Abstract: A compound with the formula I: wherein: R2 is of formula II: where A is a C5-7 aryl group, X is selected from the group comprising: NHNH2, CONHNH2, formula III, formula IV, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, 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; 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; either: (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the n
    Type: Application
    Filed: October 12, 2012
    Publication date: August 21, 2014
    Applicant: Spirogen Sàrl
    Inventor: Philip Wilson Howard
  • Patent number: 8809321
    Abstract: The present invention provides a compound of general formula A, useful as potential anticancer agents against eleven human cancer cell lines. The present invention further provides a process for the preparation of diaryl ether linked pyrrolo[2,1-c][1,4]benzodi azepine conjugates attached through different alkane spacers of general formula A.
    Type: Grant
    Filed: March 30, 2011
    Date of Patent: August 19, 2014
    Assignee: Council of Scientific and Industrial Research
    Inventors: Ahmed Kamal, Arutla Viswanath, Jayanti Naga Srirama Chandra Murty, Earla Vijaya Bharathi, Gadupudi Ramakrishna, Farheen Sulthana
  • Publication number: 20140155590
    Abstract: The present invention relates to pyrrolo[1,4]benzodiazepine (PBD) dimer conjugates, to the compositions comprising them and to their therapeutic application, in particular as anticancer agents. The invention also relates to the process for the preparation of the conjugates, to their application as anticancer agents and to the dimers themselves.
    Type: Application
    Filed: June 21, 2013
    Publication date: June 5, 2014
    Inventors: Alain Commercon, Laurence Gauzy-Lazo
  • Publication number: 20140142299
    Abstract: Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.
    Type: Application
    Filed: January 23, 2014
    Publication date: May 22, 2014
    Applicant: G1 Therapeutics, Inc.
    Inventors: Francis X. Tavares, Jay C. Strum
  • Patent number: 8722665
    Abstract: The present invention provides a compound of general formulae (8a-i), (11a-i), (14a-i), and (17a-i), useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of Cinnamido-pyrrolo[2,1-c][1,4]benzodiazepines of general formulae (8a-i), (11a-i), (14a-i), and (17a-i).
    Type: Grant
    Filed: February 27, 2009
    Date of Patent: May 13, 2014
    Assignee: Council of Scientific & Industrial Research
    Inventors: Kamal Ahmed, Balakishan Gorre, Ramakrishna Gadupudi, Sreekanth Kokkonda, Rajender
  • Publication number: 20140120118
    Abstract: A compound which is selected from A: B: and C: and salts and solvates thereof, as well as conjugates thereof with cell binding agent.
    Type: Application
    Filed: October 11, 2013
    Publication date: May 1, 2014
    Applicant: Spirogen Sàrl
    Inventor: Philip Wilson HOWARD
  • Patent number: 8710046
    Abstract: Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.
    Type: Grant
    Filed: June 30, 2010
    Date of Patent: April 29, 2014
    Assignee: Albany Molecular Research, Inc.
    Inventors: Peter R. Guzzo, David D. Manning, William Earley
  • Patent number: 8697688
    Abstract: Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.
    Type: Grant
    Filed: April 15, 2011
    Date of Patent: April 15, 2014
    Assignees: Seattle Genetics Inc., Spirogen Sarl
    Inventors: Philip Wilson Howard, Luke Masterson, Arnaud Tiberghien, Scott Jeffrey, Patrick Burke, Peter Senter
  • Publication number: 20140088089
    Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds, such as those in formulas (V)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The present invention is further directed to methods of preparing a conjugate of a cell-binding agent and a cytotoxic compound. The methods comprise the use of an imine reactive compound to enable efficient conjugations of cytotoxic compounds with cell binding agents.
    Type: Application
    Filed: February 15, 2012
    Publication date: March 27, 2014
    Applicant: ImmunoGen, INC.
    Inventor: Ravi V.J. Chari
  • Publication number: 20140080816
    Abstract: The present invention relates to tricyclic quinoline and quinoxaline derivatives, to a pharmaceutical composition containing such compounds, to their use as modulators, especially agonists or partial agonists, of the 5-HT2C receptor, their use for preparing a medicament for the prevention or treatment of conditions and disorders which respond to the modulation of 5-HT2C receptor, and to a method for preventing or treating conditions and disorders which respond to the modulation of 5-HT2C receptor.
    Type: Application
    Filed: September 13, 2013
    Publication date: March 20, 2014
    Inventors: Hannes Koolman, Wilfried Braje, Helmut Mack, Andreas Haupt, Ana Lucia Relo, Karla Drescher, Margot Bakker, Viktor Lakics, Carolin Hoft, Ruxu Xu, Xiaona Zhao
  • Publication number: 20140066435
    Abstract: Pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.
    Type: Application
    Filed: November 6, 2013
    Publication date: March 6, 2014
    Applicant: SPIROGEN SARL
    Inventors: Philip Wilson HOWARD, Luke MASTERSON, Arnaud TIBERGHIEN, Scott JEFFREY, Patrick BURKE, Peter SENTER
  • Publication number: 20140057902
    Abstract: The invention relates to compound of the formula I or a salt thereof, wherein the substituents are as defined in the specification; to its preparation, to its use as medicament and to medicaments comprising it.
    Type: Application
    Filed: August 22, 2013
    Publication date: February 27, 2014
    Applicant: NOVARTIS AG
    Inventors: Dirk BEHNKE, David CARCACHE, Peter ERTL, Manuel KOLLER, David ORAIN
  • Patent number: 8637665
    Abstract: A compound of general formula 9, useful as potential antitumor agents against human cancer cell line and a process for the preparation of Pyrrolo[2,1-c] [1,4]benzodiazepine-benzothiazole or benzoxazole conjugates linked through piperazine of general formula 9 wherein: R, R1=H, F, OCF3, Cl, OMe; R2=OCH3 or H; n1 n2=3, 4; x=S or O.
    Type: Grant
    Filed: June 18, 2012
    Date of Patent: January 28, 2014
    Assignee: Council of Scientific & Industrial Research
    Inventors: Kamal Ahmed, Rajesh V. C. R. N. C. Shetti, K. Srinivasa Reddy, Adla Malla Reddy, Ponnampally Swapna
  • Patent number: 8633185
    Abstract: 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: Grant
    Filed: November 2, 2009
    Date of Patent: January 21, 2014
    Assignee: Spirogen Sarl
    Inventors: Philip Wilson Howard, Zhizhi Chen, Stephen John Gregson
  • Publication number: 20130317011
    Abstract: The present invention provides a compound of general formula A, useful as potential anticancer agents against eleven human cancer cell lines. The present invention further provides a process for the preparation of diaryl ether linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates attached through different alkane spacers of general formula A.
    Type: Application
    Filed: March 30, 2011
    Publication date: November 28, 2013
    Applicant: COUNCIL OF SCIENCE AND INDUSTRIAL RESEARCH
    Inventors: Ahmed Kamal, Arutla Viswanath, Jayanti Naga Srirama Chandra Murty, Earla Vijaya Bharathi, Gadupudi Ramakrishna, Farheen Sulthana
  • Patent number: 8592407
    Abstract: The present invention provides synthesis and in vitro anticancer activity of novel pyrrolo[2,1-c][1,4]benzodiazepine derivatives with dithiocarbamate side chains. The present invention also relates to a process for the preparation of new pyrrolo[2,1-c][1,4]benzodiazepine derivatives with dithiocarbamate side chains of general formula (A) and a process for the preparation thereof.
    Type: Grant
    Filed: March 24, 2009
    Date of Patent: November 26, 2013
    Assignee: Council of Scientific & Industrial Research
    Inventors: Kamal Ahmed, Sreekanth Kokkonda, Praveen K. Pogula, Balakishan Gorre
  • Patent number: 8592576
    Abstract: 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)n—, 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: Grant
    Filed: October 16, 2009
    Date of Patent: November 26, 2013
    Assignee: Spirogen Sarl
    Inventors: Philip Wilson Howard, Stephen John Gregson, Luke Masterson
  • Publication number: 20130266595
    Abstract: A conjugate of formula (A): where Y is selected from a single bond, and a group of formulae A1 or A2: where N shows where the group binds to the N10 of the PBD moiety; RL1 and RL2 are independently selected from H and methyl, or together with the carbon atom to which they are bound form a cyclopropylene group; CBA represents a cell binding agent; Q is independently selected from O, S and NH; R11 is either H, or R or, where Q is O, SO3M, where M is a metal cation.
    Type: Application
    Filed: October 12, 2012
    Publication date: October 10, 2013
    Inventors: John A. Flygare, Janet L. Gunzner-Toste, Thomas Pillow, Philip Wilson Howard, Luke Masterson
  • Patent number: 8519123
    Abstract: The present invention provides a compound of general formula 7, useful as potential antitumour agents against five human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine linked imidazo[1,5-a]pyridine conjugates attached through a piperazine moiety and different alkane spacers of general formula 7 wherein R represents H, OCH3, CF3, CN, F or Cl; n=3, 4, 5 or 6.
    Type: Grant
    Filed: March 23, 2011
    Date of Patent: August 27, 2013
    Assignee: Council of Scientific and Industrial Research
    Inventors: Ahmed Kamal, Gadupudi Ramakrishna, Paidakula Raju, Ayinampudi Venkata Subba Rao, Arutla Viswanath, Gorre Balakishan
  • Publication number: 20130210804
    Abstract: The present invention is directed to tricyclic compounds which are positive allosteric modulators of metabotropic glutamate receptors, particularly the mGluR5 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.
    Type: Application
    Filed: October 20, 2011
    Publication date: August 15, 2013
    Inventors: Neville J. Anthony, Robert P. Gomez, Jing Li, Swati P. Mercer, Anthony J. Roecker, Craig A. Stump, Theresa M. Williams
  • Patent number: 8501934
    Abstract: Methods of preparing ZC-423 (I) which result in varying enantiomeric ratios.
    Type: Grant
    Filed: July 22, 2009
    Date of Patent: August 6, 2013
    Assignee: Spirogen SARL
    Inventors: Philip Wilson Howard, Stephen John Gregson, Zhizhi Chen, Arnaud Charles Tiberghien, Luke Masterson
  • Patent number: 8487092
    Abstract: 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: Grant
    Filed: October 16, 2009
    Date of Patent: July 16, 2013
    Assignee: Spirogen Developments SARL
    Inventors: Philip Wilson Howard, Stephen John Gregson, ZhiZhi Chen, Arnaud Charles Tiberghien, Luke Masterson
  • Patent number: 8481042
    Abstract: The present invention relates to pyrrolo[1,4]benzodiazepine (PBD) dimer conjugates, to the compositions comprising them and to their therapeutic application, in particular as anticancer agents. The invention also relates to the process for the preparation of the conjugates, to their application as anticancer agents and to the dimers themselves.
    Type: Grant
    Filed: February 24, 2012
    Date of Patent: July 9, 2013
    Assignee: Sanofi
    Inventors: Alain Commercon, Laurence Gauzy-Lazo
  • Patent number: 8461150
    Abstract: The present invention relates to chalcone linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids and a process for the preparation there of. More particularly it relates to 7-Methoxy-8-{n[4-1-(2 or 4-substituted phenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one]alkyl}-oxy}-(11aS)-1,2,3,11a-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one and 7-Methoxy-8-{n-[-3-(4-hydroxy-3-methoxyphenyl)-1-(2,4-alkyl-3-quinolyl)-2-propen-1-one]alkyl}-oxy-(11aS)-1,2,3,11a-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one with aliphatic chain length variations useful as anticancer (antitumor) agent. The general structural formula of these chalcone linked pyrrolo[2,1-c][1,4]benzodiazepines hybrids is given below. wherein R1=OH, methyl, ethyl or phenyl; R2=H, OH or F; R=H or methyl; x=c or N; n=1-4.
    Type: Grant
    Filed: October 31, 2008
    Date of Patent: June 11, 2013
    Assignee: Council of Scientific & Industrial Research
    Inventors: Ahmed Kamal, Bandari Rajendra Prasad, Adla Malla Reddy
  • Publication number: 20130131336
    Abstract: The present invention provides a compound of general formulae A useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of general formulae 6a-g, 10a-o, 14a-g and 18a-o.
    Type: Application
    Filed: December 3, 2010
    Publication date: May 23, 2013
    Inventors: Ahmed Kamal, Rajesh V.C.R.N.C. Shetti, Srinivasa K. Reddy, Adla Malla Reddy
  • Publication number: 20130109679
    Abstract: Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.
    Type: Application
    Filed: November 30, 2010
    Publication date: May 2, 2013
    Inventors: Stephen James Boyer, Donghong Amy Gao, Xin Guo, Thomas Martin Kirrane, JR., Christopher Ronald Sarko, Roger John Snow, Fariba Soleymanzadeh, Yunlong Zhang
  • Publication number: 20130102774
    Abstract: A process for transforming a group >C?O (I) in a compound into a group >C?S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product, by use of crystalline P2S5.2 C5H5N as a thionating agent. A thionating agent which is crystalline P2S5.2 C5H5N.
    Type: Application
    Filed: February 3, 2012
    Publication date: April 25, 2013
    Applicant: VIRONOVA AB
    Inventors: Birgitta Pettersson, Vedran Hasimbegovic, Per H Svensson, Jan Bergman
  • Patent number: 8404678
    Abstract: The invention relates to novel tomaymicine derivatives comprising a linker. It also relates to the conjugate molecules that comprise one or more of said tomaymicine derivatives covalently linked to a cell binding agent through a linking group that is present on the linker of the tomaymycin derivative. It also relates to the preparation of the tomaymicine derivatives and of the conjugate molecules.
    Type: Grant
    Filed: January 19, 2010
    Date of Patent: March 26, 2013
    Assignee: Sanofi
    Inventors: Hervé Bouchard, Ravi V. J. Chari, Alain Commerçon, Yonghong Deng, Laurence Gauzy
  • Publication number: 20130059800
    Abstract: Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.
    Type: Application
    Filed: April 15, 2011
    Publication date: March 7, 2013
    Applicants: SEATTLE GENETICS INC., SPIROGEN DEVELOPMENTS SÀRL
    Inventors: Philip Wilson Howard, Luke Masterson, Arnaud Tiberghien, Scott Jeffrey, Patrick Burke, Peter Senter
  • Patent number: 8383618
    Abstract: The present invention provides a compounds of general formula IXa-d, useful as potential antitumour agents and pharmaceutical composition comprising these compounds exhibits binding affinity with calf thymus (CT) DNA at a molar ratio of 1:5 in aqueous sodium phosphate buffer at pH of 7.00. The present invention further provides a process for the preparation of C2-Fluoro substituted piperazine linked pyrrolo[2,1c][1-4], benzodiazepine of formula (IX).
    Type: Grant
    Filed: October 31, 2008
    Date of Patent: February 26, 2013
    Assignee: Council of Scientific & Industrial Research
    Inventors: Ahmed Kamal, Rajender, Metuku Kashireddy, Gorre Balakishan
  • Patent number: 8372831
    Abstract: The present invention provides compounds of general formula (5a-d) and (9a-h) useful as potential antitumour agents against human cancer cell lines. The present invention also provides a process for the preparation of pyrrolo [2,1-c][1,4]benzodiazepine hybrids of general formula (5a-d) and (9a-h).
    Type: Grant
    Filed: October 31, 2008
    Date of Patent: February 12, 2013
    Assignee: Council of Scientific & Industrial Research
    Inventors: Kamal Ahmed, Jonnala Surendranadha Reddy, Dudekula Dastagiri, Earla Vijaya Bharathi
  • Publication number: 20130035484
    Abstract: A compound of formula (I): which is substantially free of any of the corresponding compound of formula (IB): methods of making such compounds, and the further transformation of such compounds.
    Type: Application
    Filed: April 15, 2011
    Publication date: February 7, 2013
    Applicant: SPIROGEN DEVELOPMENTS SÀRL
    Inventors: Philip Wilson Howard, Luke Masterson, Arnaud Tiberghien
  • Publication number: 20120316335
    Abstract: A compound of general formula 9, useful as potential antitumour agents against human cancer cell line and a process for the preparation of Pyrrolo[2,1-c] [1,4]benzodiazepine-benzothiazole or benzoxazole conjugates linked through piperazine of general formula 9 wherein: R, R1=H, F, OCF3, Cl, OMe; R2=OCH3 or H; n1 n2=3, 4; x=S or O.
    Type: Application
    Filed: June 18, 2012
    Publication date: December 13, 2012
    Inventors: Kamal Ahmed, Rajesh V., C., R., N., C. Shetti, K. Srinivasa Reddy, Adla Malla Reddy, Ponnampally Swapna
  • Patent number: 8318726
    Abstract: The present invention provides a compound of formula 5, useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of pyrrolo[2,1-c][1,4]benzodiazepine hybrids of formula 5a-t.
    Type: Grant
    Filed: March 15, 2011
    Date of Patent: November 27, 2012
    Assignee: Council of Scientific & Industrial Research
    Inventors: Ahmed Kamal, Adla Mallareddy, Paidakula Suresh, Rajesh Venkata Chenna Rama Narasimha Chennamshetti
  • Publication number: 20120270857
    Abstract: Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.
    Type: Application
    Filed: June 30, 2010
    Publication date: October 25, 2012
    Applicant: ALBANY MOLECULAR RESEARCH, INC.
    Inventors: Peter R. Guzzo, David D. Manning, William Earley