- SOLID FORMS OF 3-((1R,3R)-1-(2,6-DIFLUORO-4-((1-(3-FLUOROPROPYL)AZETIDIN-3-YL)AMINO)PHENYL)-3-METHYL-1,3,4,9-TETRAHYDRO-2H-PYRIDO[3,4-B]INDOL-2-YL)-2,2-DIFLUOROPROPAN-1-OL AND PROCESSES FOR PREPARING FUSED TRICYCLIC COMPOUNDS COMPRISING A SUBSTITUTED PHENYL OR PYRIDINYL MOIETY, INCLUDING METHODS OF THEIR USE
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Provided herein are solid forms, salts such as compound B, and formulations of 3-((lR,3R)-l-(2,6-difluoro-4-((l-(3-fluoropropyl) azetidin-3-yl)amino)phenyl)-3-methyl-l,3,4,9-tetrahydro-2H- pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-l-ol, processes and synthesis thereof, and methods of their use in the treatment of cancer.
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Paragraph 0411; 0420; 0421-0422; 0423-0424; 0425-0426
(2020/01/11)
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- Synthesis of Chiral Tryptamines via a Regioselective Indole Alkylation
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A practical synthesis of chiral tryptamines from simple, unprotected indoles has been developed. Indole nucleophiles prepared with MeMgCl in the presence of CuCl reacted with chiral cyclic sulfamidates almost exclusively at the C3-position of i
- Wolfard, Jens,Xu, Jie,Zhang, Haiming,Chung, Cheol K.
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supporting information
p. 5431 - 5434
(2018/09/12)
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- INDANE DERIVATIVES AS MGLUR7 MODULATORS
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The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4a and R4b are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds of formula (I) are mGluR7 modulators.
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Page/Page column 89
(2017/08/21)
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- N-ACYLETHANOLAMINE HYDROLYZING ACID AMIDASE (NAAA) INHIBITORS AND THEIR USE THEREOF
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A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA). The present technology is directed to compounds, compositions, and methods to inhibit N-acylethanolamine hydrolyzing acid amidase and to treat N-acylethanolamine hydrolyzing acid amidase mediated conditions in a subject.
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Paragraph 0247
(2015/12/08)
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- Amino-benzosuberone: A novel warhead for selective inhibition of human aminopeptidase-N/CD13
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This paper describes the design and synthesis of compounds belonging to a novel class of highly selective mammalian CD13 inhibitors. Racemic homologues of 3-amino-2-tetralone 1 were synthesised and evaluated for their ability to selectively inhibit the me
- Albrecht, Sebastien,Al-Lakkis-Wehbe, Mira,Orsini, Alban,Defoin, Albert,Pale, Patrick,Salomon, Emmanuel,Tarnus, Celine,Weibel, Jean-Marc
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experimental part
p. 1434 - 1449
(2011/04/12)
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- The enantioselective benzoin condensation promoted by chiral triazolium precatalysts: Stereochemical control via hydrogen bonding
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The design of a new class of triazolium ion precatalysts incorporating protic substituents is described. These materials promote the enantioselective benzoin condensation of a range of aromatic aldehydes (1-62% ee). Catalyst evaluation studies strongly support the involvement of hydrogen bond donation by the catalyst in the stereocentre-forming step of the catalytic cycle.
- O'Toole, Sarah E.,Connon, Stephen J.
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experimental part
p. 3584 - 3593
(2010/01/06)
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- Heteroaryl compounds useful as inhibitors of E1 activating enzymes
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This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.
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Page/Page column 86
(2008/06/13)
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- Inhibitors of E1 activating enzymes
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This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.
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Page/Page column 64
(2010/11/28)
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- Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications
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We previously reported a series of enantiopure cis-(1R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa Ki of 0.50 nM, PT EC2x of 2.1 μM in human plasma, bioavailability of 25% and t1/2of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented.
- Qiao, Jennifer X.,Wang, Tammy C.,Wang, Gren Z.,Cheney, Daniel L.,He, Kan,Rendina, Alan R.,Xin, Baomin,Luettgen, Joseph M.,Knabb, Robert M.,Wexler, Ruth R.,Lam, Patrick Y.S.
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p. 5041 - 5048
(2008/02/13)
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- CYCLIC DIAMINES AND DERIVATIVES AS FACTOR XA INHIBITORS
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The present application describes cyclic diamino compounds, derivatives thereof, and pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.
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Page/Page column 64
(2008/06/13)
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- HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
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A compound of the formula (1) or a pharmaceutically-acceptable salt, or pro-drug thereof; (1) wherein, for example: R4 and R5 together are either -S-C(R6=C(R7)- or -C(R7)=C(R6)-S- ; R6 and R7 are independently selected from hydrogen and halo; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is halo, cyano or carboxy; R2 is for example methyl; R3 is for example selected from halo(1-4C)alkyl, dihalo(1-4C)alkyl, trifluoromethyl, hydroxy(1-4C)alkyl, dihydroxy(2-4C)alkyl, trihydroxy(3-4C)alkyl, cyano(1-4C)alkyl (optionally substituted on alkyl with hydroxy), (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkoxy(1-4C)alkyl, di[(1-4C)alkoxy](1-4C)alkyl, (hydroxy)[(1-4C)alkoxy](1-4C)alkyl; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.
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- INDOL-2-AMIDES AS GLYCOGEN PHOSPHORYLASE INHIBITORS
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A compound of the formula (1) or a pharmaceutically-acceptable salt, or pro-drug thereof; (1) wherein, for example, R 4 is halo or (1-4C)alkyl ; A is phenylene or heteroarylene; n is 0, 1 or 2; m is 0, 1 or 2; R 1 is halo, cyano or carboxy; R 2 is for example methyl; R 3 is for example selected from halo(1-4C)alkyl, dihalo(1-4C)alkyl, trifluoromethyl, hydroxy(1-4C)alkyl, dihydroxy(2-4C)alkyl, trihydroxy(3-4C)alkyl, cyano(1-4C)alkyl (optionally substituted on alkyl with hydroxy), (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkoxy(1-4C)alkyl, di[(1-4C)alkoxy](1-4C)alkyl, (hydroxy)[(1-4C)alkoxy](1-4C)alkyl; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.
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Page/Page column 58-59
(2010/02/11)
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- INDOLAMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
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A compound of the formula (1) or a pharmaceutically-acceptable salt, or pro-drug thereof; wherein: A is phenylene or heteroarylene; n is 0, 1 or 2; m is 0, 1 or 2; R' is for example selected from halo, nitro, cyano, hydroxy, carboxy, carbamoyl, N-(1-4C)al
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Page/Page column 47
(2008/06/13)
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- HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSES GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
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A compound of the formula (1) or a pharmaceutically-acceptable salt thereof wherein: R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; A is phenylene or heteroarylene; Rsup
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Page/Page column 52-53
(2010/02/11)
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- Convenient method for the kinetic resolution of β-aminoalcohols
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A variety of easily removable protecting groups were tested in the kinetic resolution of N-protected β-aminoalcohols using chiral catalysts derived from N-4′-pyridinyl-α-methyl proline. The trifluoroacetyl group was the most promising protecting group as it gave the highest selectivities with all alcohols tested and can easily be removed without loss of enantiomeric excess. This strategy constitutes a convenient method for the kinetic resolution of β-aminoalcohols.
- Pelotier, Béatrice,Priem, Ghislaine,Macdonald, Simon J.F.,Anson, Mike S.,Upton, Richard J.,Campbell, Ian B.
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p. 9005 - 9007
(2007/10/03)
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- LACTAM-CONTAINING CYCLIC DIAMINES AND DERIVATIVES AS FACTOR XA INHIBITORS
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The present application describes lactam-containing cyclic diamines and derivatives thereof of Formula I: or pharmaceutically acceptable salt forms thereof, wherein M is a non-aromatic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trysin-like serine proteases, specifically factor Xa.
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Page/Page column 119
(2010/02/08)
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- HETEROCYCLIC AMIDE DERIVATIVES HAVING GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
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Heterocyclic amides of formula (1) wherein: Z is CH or nitrogen; R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S- ; R6 and R7 are selected from for example hydrogen, halo, C1-4alkyl, and C1-4alkanoyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; r is 1 or 2; Y is -NR2R3 or -OR3; R2 and R3 are selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl (optionally substituted by 1 or 2 R8 groups); R4 is selected from for example hydrogen, halo, nitro, cyano, hydroxy, C1-4alkyl, and C1-4alkanoyl; R8 is selected from for example hydroxy, -COCOOR9, -C(O)N(R9)(R10), -NHC(O)R9 , (R9)(R10)N- and -COOR9 ; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13 ); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.
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Page/Page column 105
(2010/02/07)
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- Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors
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Heterocyclic amide derivatives, of formula (I): wherein —X-Y-Z- is selected from —S—CR4═CR5—, —CR4═CR5—S—, —O—CR4═CR5—, —CR4═CR5—O—, —N═CR4—S—, —S—CR4═N—, —NR6—CR4═CR5— and —CR4═CR5—NR6—; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof; (with provisos); possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.
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- Synthesis of enantiomerically pure cis- and trans-1,2- diaminoindanes
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The four isomers of cis- and trans-1,2-diaminoindanes 5 and 11 were prepared in three steps and high enantiomeric excess by a key lipase- catalyzed selective transesterification of racemic cis-2-azido-1-indanol and trans-1-azido-2-indanol, respectively.
- Bit, Christelle,Mitrochkine, Anton A.,Gil, Gerard,Pierrot, Marcel,Reglier, Marius
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p. 3263 - 3273
(2007/10/03)
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