- SPECT imaging agent for FAP-alpha specific tumor diagnosis
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The invention relates to an SPECT imaging agent for FAP-alpha specific tumor diagnosis. The imaging agent is formed by taking a micromolecular FAP-alpha inhibitor of a modified N-4-quinolyl-glycine-(2S)-cyanoproline skeleton as a precursor compound, taking 99mTc as radionuclide and taking N-tris (hydroxymethyl) methylglycine (Tricine) and triphenylphosphine tri-m-sodium sulfonate (TPPTS) as synergistic ligands. Compared with the prior art, the imaging agent has high sensitivity, more excellent in-vivo biological distribution is shown, compared with the prior art, the complex has the advantagesof higher tumor uptake and tumor/organ uptake ratio, more stable coordination property, and excellent in-vivo and in-vitro stability. Due to the obvious coordination structure characteristics of theimaging agent, a one-step marking kit technology can be used, and the imaging agent has better druggability and is suitable for industrial production and clinical popularization.
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- INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN
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Compounds and compositions for modulating fibroblast activation protein (FAP) are described. The compounds and compositions may find use as therapeutic agents for the treatment of diseases, including hyperproliferative diseases.
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Paragraph 0496; 0499-0500
(2019/07/03)
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- HEPATITIS B ANTIVIRAL AGENTS
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The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepati
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Page/Page column 43; 44
(2017/02/09)
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- DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS
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Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer,
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Paragraph 00294
(2015/06/08)
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- Extended structure-activity relationship and pharmacokinetic investigation of (4-quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP)
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Fibroblast activation protein (FAP) is a serine protease related to dipeptidyl peptidase IV (DPPIV). It has been convincingly linked to multiple disease states involving remodeling of the extracellular matrix. FAP inhibition is investigated as a therapeutic option for several of these diseases, with most attention so far devoted to oncology applications. We previously discovered the N-4-quinolinoyl-Gly-(2S)-cyanoPro scaffold as a possible entry to highly potent and selective FAP inhibitors. In the present study, we explore in detail the structure-activity relationship around this core scaffold. We report extensively optimized compounds that display low nanomolar inhibitory potency and high selectivity against the related dipeptidyl peptidases (DPPs) DPPIV, DPP9, DPPII, and prolyl oligopeptidase (PREP) the log D values, plasma stabilities, and microsomal stabilities of selected compounds were found to be highly satisfactory. Pharmacokinetic evaluation in mice of selected inhibitors demonstrated high oral bioavailability, plasma half-life, and the potential to selectively and completely inhibit FAP in vivo.
- Jansen, Koen,Heirbaut, Leen,Verkerk, Robert,Cheng, Jonathan D.,Joossens, Jurgen,Cos, Paul,Maes, Louis,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
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p. 3053 - 3074
(2014/05/06)
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- NOVEL FAP INHIBITORS
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The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
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Paragraph 0281; 0294; 0295; 096; 0297; 0298
(2014/12/09)
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- NOVEL FAP INHIBITORS
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The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
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- NEW COMPOUNDS
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The invention relates to new compounds of the general formula (I), which are strong DPP-IV enzyme inhibitors.
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Page/Page column 20
(2008/06/13)
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- PYRROLIDINE-2-CARBONITRILE DERIVATIVES AND THEIR USE AS INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DPP-IV)
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The present invention relates to compounds of formula (I), (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, b-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
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Page/Page column 72
(2008/06/13)
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- Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
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The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, β-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
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Page/Page column 31-32; 34
(2010/02/12)
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- Synthesis and structure-activity relationships of potent 3- or 4-substituted-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors
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A series of 3- or 4-substituted-2-cyanopyrrolidines were synthesized and evaluated as dipeptidyl peptidase IV inhibitors. Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. A series of 2-cyanopyrrolidines are among the most potent of DPP-IV inhibitors. We focused our attention on substitutions at the 3- or 4-position of 2-cyanopyrrolidines and synthesized and evaluated various derivatives. Among them, the 4-fluoro derivative was found to exhibit better DPP-IV inhibitory activity and higher plasma drug concentrations after oral administration to rats than the 4-unsubstituted derivative. We report here on the synthesis and biological data of the aforementioned derivatives.
- Fukushima, Hiroshi,Hiratate, Akira,Takahashi, Masato,Saito, Masako,Munetomo, Eiji,Kitano, Kiyokazu,Saito, Hidetaka,Takaoka, Yuji,Yamamoto, Koji
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p. 6053 - 6061
(2007/10/03)
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- 2-CYANOPYRROLIDINE DERIVATIVES AND THEIR USE AS DPP-IV INHIBITORS
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A compound of the formula (I) or a pharmaceutically acceptable salt thereof: [wherein X is CFH, or CF?2#191, R?1? is the moiety represented by the formula: [wherein R?2? is (lower) alkyl, R?3? is phenyl-(lower)alkyl, and the like.], and the like.] Compounds of formula (I) inhibit DPP-IV activity. They are therefore useful in the treatment of conditions mediated by DPP-IV, such as NIDDM.
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- NEW COMPOUNDS
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The present invention relates to new, potent DPP-IV enzyme inhibitors of the general formula (I), which contain fluorine atoms.
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Page/Page column 15-16
(2008/06/13)
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- CYANOPYRROLIDINE DERIVATIVES
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A cyanopyrrolidine derivative represented by Formula (1): [wherein R1 is a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, R2 is a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, or R1 and R2 together form an oxo, a hydroxyimino group, an alkoxyimino group having 1 to 5 carbon atoms or an alkylidene group having 1 to 5 carbon atoms, ???R3 and R4 are each a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or an alkyl group having 1 to 5 carbon atoms, or R3 and R4 together form an oxo, a hydroxyimino group, an alkoxyimino group having 1 to 5 carbon atoms or an alkylidene group having 1 to 5 carbon atoms, ???X is an oxygen atom or a sulfur atom, ???Y is -CR5R6- (wherein R5 and R6 are the same or different, and are each a hydrogen atom, a halogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms or an optionally substituted alkenyl group having 2 to 10 carbon atoms), or -CR7R8-CR9R10- (wherein R7, R8, R9 and R10 are the same or different, and each a hydrogen atom, a halogen atom or an optionally substituted alkyl group having 1 to 10 carbon atoms, or R7 and R9 together with the carbon atom to which they are attached form an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, an optionally substituted cycloalkenyl group having 4 to 8 carbon atoms, an optionally substituted bicycloalkyl group having 5 to 10 carbon atoms, or an optionally substituted bicycloalkenyl group having 5 to 10 carbon atoms) and ???Z is a hydrogen atom or an optionally substituted alkyl group having 1 to 10 carbon atoms, or Y and Z together with the nitrogen atom to which they are attached form an optionally substituted cyclic amino group having 2 to 10 carbon atoms], or a pharmaceutically acceptable salt thereof.
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