73161-37-2Relevant articles and documents
Synthesis of carbo- and heterofused 5-amino-2H-1,2-thiazine 1,1-dioxides via the CSIC reaction strategy
Chuchvera, Yaroslav O.,Dobrydnev, Alexey V.,Dyachenko, Maksim S.,Frolov, Andriy I.,Ostapchuk, Eugeniy N.,Popova, Maria V.,Volovenko, Yulian M.
, (2022/02/21)
Herein, we present a full account of our studies with respect to the synthesis of carbo- and heterofused β-enamino-δ-sultams annelated on face c (3,4-bond). This class of compounds was designed as isomeric counterpart of known pharmacological templates – fused δ-sultams annelated through a face e (5,6-bond) following the principles of bioisosteric replacement. The starting material for this synthesis is cyclic vicinal amino nitriles. In particular, several methods were developed for methanesulfonylation of 5- and 6-membered carbo- and heteroaromatic as well as sp3-enriched β-enamino nitriles depending on their chemical nature and reactivity. The obtained N-mono- or/and N,N-dimesylates were converted into the corresponding N-methylmethanesulfonamides, which were subjected to the CSIC (Carbanion-mediated Sulfonate (Sulfonamide) Intramolecular Cyclization) reaction protocols thus affording target carbo- and heterofused β-enamino-δ-sultams. Their synthetic utility was demonstrated by the reactions with carbo- and hetero electrophiles.
SUBSTITUTED PYRIMIDINES, PHARMACEUTICAL COMPOSITIONS AND THERAPEUTIC METHODS THEREOF
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Paragraph 00276, (2019/03/17)
The invention provide novel pyrimidine derivatives and analogs having inhibitory activities towards certain tyrosine kinases, e.g., Bruton's tyrosine kinase (Btk) and/or Focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), pharmaceutical compositions thereof, and methods of treatment, reduction or prevention of certain diseases or conditions mediated by such by tyrosine kinases, e.g., cancers, tumors, fibrosis, inflammatory diseases, autoimmune diseases, diabetes, or immunologically mediated diseases.
PYRAZOLOPYRIDINES AND PYRAZOLOPYRIMIDINES
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Paragraph 0723, (2015/12/26)
A compound having the structure: or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A and A′ are independently C or N, where C may be unsubstituted or substituted by halo or C1-C6 alkyl; R and R0 are independently selected from the group consisting of H, C1-C6 alkyl, hydroxy(C1-C6 alkyl), phenyl(C1-C6 alkyl), and —(CH2)n—W, where W is C3-C8 cycloalkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1-3 N, S and/or O atoms, —SO2—R′, —NHSO2—R′, —NR″SO2—R′ and SR′, where R′ and R″ are independently C1-C6 alkyl or C3-C8 cycloalkyl, etc.; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, etc.; or, R and R0 and the N atom to which they are bonded together form a monocyclic or bicyclic heterocyclic ring which may be unsubstituted or substituted by (a) halo, hydroxy, heteroaryl, C1-C6 alkyl, C1-C6 alkoxy, etc., or (b) —(CH2)n—W, where W is C3-C8 cycloalkyl, phenyl, etc.; R1 is H, halo or cyano; R2 and R2′ are independently H, C1-C6 alkyl, cyano, C1-C6 alkoxy, C1-C6 alkylthio, or C3-C8 cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms; X is a bond, —CO—, —CONH—, —SO2—, —SONH—, or —(CH2)m—; R3 is H, C1-C4 alkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1-3 N atoms, a 5-membered heteroaryl or heterocyclic, etc., or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent —Y—R4 and/or 1-4 substituents each independently selected from R5; with the proviso that when X is —CO— or —SO2—, R3 is not H; Y is a bond, —(CH2)m— or —O—; R4 is (a) H, C1-C6 alkyl, C3-C8 cycloalkyl, halo, oxo, —OR6, —NR7R8, —SR6, —SOR9, —SO2R9, —COR6, —OCOR6, —OCOR6, —NR6COR6, —CONR7R8, etc.; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1-5 substituents selected from C1-C6 alkyl, C3-C8 cycloalkyl, halo, cyano, —OR6, —NR7R8, etc.; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, etc.; R6 is H, C1-C6 alkyl or C3-C8 cycloalkyl, etc.; R7 and R8 are each independently H, C1-C6 alkyl or C3-C8 cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1-2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C1-C6 alkyl is optionally substituted by C3-C8 cycloalkyl, halo, etc., and said heterocyclic ring being optionally substituted by one or more C1-C6 alkyl or C3-C8 cycloalkyl groups; R9 is C1-C6 alkyl or C3-C8 cycloalkyl; and, m and n are independently 0, 1, 2 or 3. The invention also relates to pharmaceutically acceptable salts of these compounds and to pharmaceutically acceptable solvates thereof; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly asthma and COPD.
