- SUBSTITUTED STRAIGHT CHAIN SPIRO DERIVATIVES
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Provided herein are pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, pharmaceutical composition comprising such compounds, and their use as menin/MLL protein/protein interaction inhibitors, useful for treating diseases such as cancer, including but not limited to leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN); and diabetes.
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Page/Page column 86
(2021/06/26)
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- ANTIBODY DRUG CONJUGATES
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The present disclosure provides antibody drug conjugates comprising STING modulators. Also provided are compositions comprising the antibody drug conjugates. The compounds and compositions are useful for stimulating an immune response in a subject in need thereof. Formula (I):
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Paragraph 0630; 0632
(2020/11/30)
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- DC-SIGN ANTIBODY CONJUGATES COMPRISING STING AGONISTS
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Provided herein are immunoconjugates comprising an anti-DC-SiGN antibody conjugated to a STING agonist. Also disclosed are methods of making the immunoconjugates and methods of treating cancer using the immunoconjugates.
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Page/Page column 597
(2020/05/29)
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- The Role of N-Methyl Squaramides in a Hydrogen-Bonding Strategy to Fold Peptidomimetic Compounds
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Small peptides and peptomimetic compounds are valuable tools to probe and study biological systems. Small synthetic peptide analogues adopt a given secondary structure driven by structural modules that organize the compound architecture. Among them, β- an
- Martínez-Crespo, Luís,Escudero-Adán, Eduardo C.,Costa, Antonio,Rotger, Carmen
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p. 17802 - 17813
(2018/11/23)
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- AZACARBOLINE DERIVATIVES, PREPARATION METHOD THEREOF AND THERAPEUTIC USE OF SAME
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The invention relates to novel azacarbonlines having formula (I), wherein: R3, R4 represent independently H; hal; CF3; substituted oxy, optionally substituted alkoxy; optionally substituted amino; substituted carbonyl; optionally substituted carboxyl; optionally substituted amide; sulphur, such as optionally substituted sulphones, sulphoxides or sulphides; linear, branched or cyclic C1-C10 alkyl optionally comprising an optionally substituted heteroatom; optionally substituted linear, branched or cyclic C2-C7 alkenyl; optionally substituted linear or branched C2-C6 alkynyl; optionally substituted aryl or heteroaryl; of which may be optionally substituted; in the form of a base or an acid addition salt. The invention also relates to the use of same in therapeutics for the treatment of cancer and to synthesis methods.
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Page/Page column 28-29
(2011/08/04)
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- Design, synthesis, and cyclization of 4-aminobutyric acid derivatives: Potential candidates as self-immolative spacers
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Self-immolative spacers have gained significant interest in recent years due to their utility in numerous prodrug, sensor and drug delivery systems. However, there are a very limited number of spacers that are capable of undergoing spontaneous and rapid reactions under mild conditions. To address this need, 4-aminobutyric acid derivatives were explored as a potential class of self-immolative spacers. Using a modular approach, eleven N- and α-substituted derivatives of 4-aminobutyric acid were synthesized, and their intramolecular cyclizations to γ-lactams were studied. Kinetics experiments were carried out at physiological pH and temperature, and the observed half-lives for the spacers ranged from 2 to 39 s, depending on the molecular structure. In addition, the pH dependence of the cyclization rate was also explored and it was found that cyclization still occurred rapidly at mildly acidic pH. Therefore, this class of compounds exhibits promise for incorporation into a variety of self-immolative systems where rapid cyclization reactions are desired.
- Dewit, Matthew A.,Gillies, Elizabeth R.
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experimental part
p. 1846 - 1854
(2011/05/03)
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- DIAMIDE COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND β2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
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This invention relates to a compound of formula I; or a pharmaceutically acceptable salt thereof. Such compounds possess both muscarinic receptor antagonist and β2 adrenergic receptor agonist activities. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds, and methods of using such compounds as bronchodilating agents to treat pulmonary disorders.
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Page/Page column 59
(2010/11/05)
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- Renin Inhibitors
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Disclosed are compounds having the formula (I): wherein the R1, R2, R3, X, Y, A, L, and G are defined herein. These compounds bind to aspartic proteases to inhibit their activity and are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also disclosed are methods of use of the compounds of Formula I for ameliorating or treating aspartic protease related disorders in a subject in need thereof.
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Page/Page column 54
(2010/12/29)
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- NITROGEN-BASED LINKERS FOR ATTACHING MODIFYING GROUPS TO POLYPEPTIDES AND OTHER MACROMOLECULES
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The present invention relates to a compound comprising a peptide moiety, a linker moiety and a water-soluble polymer moiety such as a poly(ethylene glycol) moiety. The linker moiety is between the peptide moiety and the water-soluble polymer moiety. In certain embodiments, the linker moiety has the structure: wherein α, β, and γ are each integers whose values are independently selected. In other embodiments the linker moiety has the following structure: wherein κ, ρ, and τ are each integers whose values are independently selected. In other embodiments the linker moiety has the following structure: wherein χ, φ, γ, and η are each integers whose values are independently selected. Alternatively, the linker structure may have the following structure: wherein λ and μ are each integers whose values are independently selected.
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Page/Page column 41
(2009/03/07)
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- Synthesis and evaluation of xanomeline analogs-Probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor
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A series of xanomeline analogs were synthesized and evaluated for binding at the M1 muscarinic acetylcholine receptor (M1 receptor). Specifically, compounds that substitute the O-hexyl chain of xanomeline with polar, ionizable, or conformationally restricted moieties were assessed for their ability to bind to the M1 receptor in a wash-resistant manner (persistent binding). From our screen, several novel ligands that persistently bind to the M1 receptor with greater affinity than xanomeline were discovered. Results indicate that persistent binding may arise not only from hydrophobic interactions but also from ionic interactions with a secondary M1 receptor binding site. Herein, a qualitative model that accounts for both binding scenarios is proposed and applied to understand the structural basis to wash-resistant binding and long-acting effects of xanomeline-based compounds.
- Kane, Brian E.,Grant, Marianne K.O.,El-Fakahany, Esam E.,Ferguson, David M.
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p. 1376 - 1392
(2008/09/18)
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- Chemokine receptor binding heterocyclic compounds with enhanced efficacy
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The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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Page/Page column 32-33
(2010/02/03)
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- NOVEL ALKYLAMINO DERIVATIVES
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Compounds represented by the following formula, such as (R,S)-1-(1-adamantyl)-2-[4-(6-chloro-2-iminobenzothiazolin-3-ylmethyl)piperidin-1-yl]ethanol, or salts thereof: X-Q-C(R1)(R2)-Z wherein R1and R2each represents hydrogen, alkyl, etc. and Z represents either of groups (a) and (b), [wherein R3represents alkyl, etc.; p is an integer of 3 to 8; R4and R5each represents hydrogen, alkyl, etc.; and B represents formula (c) (wherein R6and R7each represents hydrogen, halogeno, etc. and D represents sulfur, oxygen, etc.)].
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- DIARYLSULTAM DERIVATIVES
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Compounds represented by the formula: A-C(X)(Y)-C(R1)(R2)-Z, wherein Z represents, for example, a group of -N(R3)-(CH2)p-B wherein R3is alkyl group or other; p is integer of 3 to 8; B is a group represented by the following formula: wherein R7, R8, R9and R10represent hydrogen atom, halogen atom, alkyl group or other; X' is -S-, S(O)-, -S(O)2-, -O-, or -N(R11)- wherein R11is hydrogen atom, alkyl group or acyl group; W and W' represent benzene ring, or 5- to 7-membered heteroaryl group; X is cycloalkyl group, aryl group or other; Y is hydrogen atom, alkyl group, alkenyl group or other; A is -O-R6wherein R6is hydrogen atom, alkyl group, cycloalkyl group etc.; and R1and R2represent hydrogen atom, alkyl group or other. The compounds have high affinity and selectivity for sigma 2 binding site, and therefore they are useful as selective sigma 2 ligands for therapeutic and/or preventive treatment of various diseases and symptoms caused by sigma 2 ligands.
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