201054-55-9Relevant academic research and scientific papers
POLYFLUORINATED COMPOUNDS ACTING AS BRUTON TYROSINE KINASE INHIBITORS
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Paragraph 0498; 0499, (2016/08/17)
Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.
Total synthesis of (-)-agelastatin A
Yoshimitsu, Takehiko,Ino, Tatsunori,Tanaka, Tetsuaki
supporting information; experimental part, p. 5457 - 5460 (2009/06/06)
(Chemical Equation Presented) A new route to (-)-agelastatin A is reported. The requisite nitrogen functionalities of the agelastatin core have been installed by intramolecular aziridination of an azidoformate and subsequent regioselective azidation, lead
Concise syntheses of enantiomerically pure protected 4-hydroxypyroglutamic acid and 4-hydroxyproline from a nitroso-cyclopentadiene cycloadduct
Huang, Weiqiang,Miller, Marvin J.
experimental part, p. 2835 - 2838 (2009/06/28)
O-TBS-protected methyl trans-4-hydroxypyroglutamate and methyl trans-4-hydroxyproline ester were synthesized from nitroso-cyclopentadiene Diels-Alder cycloadducts. Enzymatic resolution of the key intermediate, 4-amino-cyclopent-2-enol, provides access to both l- and d-amino acids.
Chemoenzymatic asymmetric total synthesis of phosphodiesterase inhibitors: Preparation of a polycyclic pyrazolo[3,4-d]pyrimidine from an acylnitroso Diels-Alder cycloadduct-derived aminocyclopentenol
Jiang, May Xiao-Wu,Warshakoon, Namal C.,Miller, Marvin J.
, p. 2824 - 2827 (2007/10/03)
(Chemical Equation Presented) Enzymatic resolution of Boc-protected 4-aminocyclopenten1-ol 4c gave both enantiomers 5c and 6c in high ee. Boc removal and separate condensation with chloropyrazolopyrimidine 18 provided elaborated 1,4-aminocyclopentenol derivatives 20 and 26, respectively. Separate treatment of 20 and 26 with Pd(0) under basic conditions induced cyclization to unsaturated polycycles 22 and 27, which, upon catalytic hydrogenation, were transformed to new cyclopentane-containing pyrazolopyrimidines 24 and 28, analogues of recently described novel phosphodiesterase inhibitors.
IMPROVEMENTS IN PHARMACEUTICALLY USEFUL COMPOUNDS
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Page 45-46, (2010/11/30)
A compound of formula (I) or (II): wherein A is hydrogen or CR1R2; Y and Z are each, independently, hydrogen or a halogen;X is -NR4R5, or R7; R1 is hydrogen, or a substituted or unsubstituted alkyl or alkenyl group containing 1-4 carbon atoms; when X is -NR4R5, R2 is a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, aralkyl aralkenyl, or aralkynyl group, that optionally includes at least one heteroatom in its carbon skeleton and contains 1-12 carbon atoms; when X is R7, R2 is an unsubstituted alkyl, alkenyl or alkynyl group, or a substituted or unsubstituted aryl, aralkyl aralkenyl, or aralkynyl group, that optionally includes at least one heteroatom in its carbon skeleton and contains 1-12 carbon atoms; R3 is a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, aralkyl aralkenyl, or aralkynyl group, that optionally includes at least one heteroatom in its carbon skeleton and contains 1-12 carbon atoms; R4 is hydrogen, a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, aralkyl aralkenyl, or aralkynyl group, that optionally includes at least one heteroatom in its carbon skeleton and contains 1-12 carbon atoms, -COOR8, or -COR8; R5 is hydrogen, or a substituted or unsubstituted alkyl or alkenyl group containing 1-5 carbon atoms; R7 is an unsubstituted alkyl, alkenyl, or alkynyl group, that contains 1-4 carbon atoms; and, R8 is an unsubstituted or halo-substituted alkyl, aryl, or aralkyl group, that contains 1-12 carbon atoms.
Chiral base route to functionalised cyclopentenyl amines: Formal synthesis of the cyclopentene core of nucleoside Q
Oxenford, Sally J.,O'Brien, Peter,Shipton, Mark R.
, p. 9053 - 9055 (2007/10/03)
A chiral base route to a range of highly functionalised amino cyclopentenes has been developed. The key asymmetric step involved the chiral lithium amide base-mediated rearrangement of a protected trans-4-hydroxy cyclopentene oxide to give an allylic alcohol (88% ee). Subsequent Overman rearrangement gave a protected trans-1,2-aminocyclopentenol whereas Mitsunobu substitution with BocNHNs gave a protected cis-amino cyclopentenol. Both are proven intermediates for natural product synthesis. The protected cis-aminocyclopentenol was transformed in a few steps into a precursor of the cyclopentene core of nucleoside Q, a natural product whose deficiency in animals is related to tumour growth.
Chemoenzymatic synthesis and synthetic application of enantiopure aminocyclopentenols: Total synthesis of carbocyclic (+)-uracil polyoxin C and its α-epimer
Li, Fangzheng,Brogan, John B.,Gage, Jennifer L.,Zhang, Deyi,Miller, Marvin J.
, p. 4538 - 4540 (2007/10/03)
Carbocyclic uracil polyoxin C (+)-2 and its α-epimer (-)-3 were synthesized in an efficient fashion from cis-4-(N-tert-butylcarbamoyl)cyclopent- 2-en-1-ol (±)-7. The synthesis incorporates a concise, inexpensive chemoenzymatic synthesis of enantiopure ami
Synthetic application of acylnitroso Diels-Alder derived aminocyclopentenols: Total synthesis of (+)-streptazolin
Li, Fangzheng,Warshakoon, Namal C.,Miller, Marvin J.
, p. 8836 - 8841 (2007/10/03)
Concise total syntheses of (+)-streptazolin 1 and its more stable dihydro derivative 2 were accomplished via an intramolecular aldol condensation strategy starting from readily available aminocyclopentenol (-)-7. The synthetic sequence included reductive amination, stereoselective epoxidation, intramolecular aldol (and condensation) reaction, and Wittig reaction. The overall yield for dihydro derivative 2 from aminocyclopentenol (-)-7 was about 7% for a total of 14 steps.
Synthesis of 4-azacyclopent-2-enones and 5,5-dialkyl-4-azacyclopent-2- enones
Dauvergne, Jér?me,Happe, Alan M.,Jadhav, Vasudev,Justice, David,Matos, Marie-Christine,McCormack, Peter J.,Pitts, Michael R.,Roberts, Stanley M.,Singh, Sanjay K.,Snape, Timothy J.,Whittall, John
, p. 2559 - 2567 (2007/10/03)
Three different methods are reported for the preparation of 4-azacyclo-2-enones 1, two of which allow the preparation of the compounds in optically active form. In addition, a facile route to 4-aza-5,5- dimethylcyclopent-2-enones 2 is disclosed.
