A. I. Vogel, Preparatyka organiczna (WNT Warszawa,), p. Zielińska J., Makowski M., Maj K., Liwo A., Chmurzyński L.() Anal. A.I. Vogel. Preparatyka Organiczna, WNT, Warszawa (), p. F.V. Lovecchio, E.S. Gore, D.H. Bush. J. Am. Chem. Soc., 96 (), p. Soc. (), p. A.I. Vogel. Preparatyka Organiczna W.N.T. Warszawa ( ), p. C.G. Hatchard, C.A. Parker. Proc. Roy. Soc., A (), p.
|Published (Last):||24 July 2014|
|PDF File Size:||16.49 Mb|
|ePub File Size:||2.49 Mb|
|Price:||Free* [*Free Regsitration Required]|
The present disclosure provides a process of making certain PI3K inhibitors and compound intermediates thereof. Compound 78 is shown below.
Compound was prepared following steps A-D below, and using compound below in step A. Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e. Compound 22 is shown below. The Science prepatatyka Practice of Pharmacy, R.
In one embodiment, the application discloses a process for synthesizing a compound of formula A process comprising step a combining a compound of formula 9. Transdermal administration includes passive or active transdermal or transcutaneous modalities, including, for example, patches and iontophoresis devices, as well as topical application of pastes, salves, or ointments.
The present PI3-kinase inhibitors had an inhibitory effect on osteoclast function. Exemplary pharmaceutically acceptable salts include acid addition salts formed preparaytka inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, lactic acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, 2-napththalenesulfonic acid, oleic acid, palmitic acid, propionic acid, stearic acid, succinic acid, tartaric acid, p-toluenesulfonic acid, trimethylacetic acid, and the like, and salts formed when an acidic proton present in the parent compound is replaced by either a metal ion, e.
Remington’s Pharmaceutical Sciences oraniczna Ed. In some embodiments, R 1 is selected from the group consisting of halo and C 1 -C 8 alkyl; R 2 is selected from the group consisting of H and C 1 -C 8 alkyl, and R 3 and R 4 are each independently selected from the group consisting of an amino protective group and an optionally substituted purinyl group.
More specifically, three of the catalytic subunits, i. Compound 73 was prepared using the general procedure described above with respect to compound 14, preparatyyka 2-aminochlorobenzoic acid was substituted for 2-aminomethylbenzoic acid, and 3-fluoroaniline was substituted for aniline in step A, 2-tert-butoxycarbonylamino-propionic acid 2,5-dioxopyrrolidinyl ester was substituted for 2-benzyloxycarbonylaminobutyric acid 2,5-dioxo-pyrrolidinyl ester in step B, the alternate procedure TFA deprotection was used in step C, and 2-aminobromopurine was substituted for 6-bromopurine in step D.
Compound 82 is shown below. Another aspect of the present invention is to provide a method of treating a medical condition mediated by neutrophils pfeparatyka administering to a mammal in need thereof a therapeutically effective amount of a compound of structural formulae I or II. The process of claim 2wherein step d is performed at a temperature between 35 and degrees Celsius. In some embodiments, compositions may comprise a multi-kilogram amount of a compound of a formula disclosed herein or salt thereof.
Preparatyka organiczna vogel pdf download
The preparation of compound is generally shown above as step D of Procedure C. Notice of Allowance mailed on Oct. Vogel preparatyka organiczna instrukcje wicze laboratoryjnych dla studentw iii. N,N-Diethylhydroxylamine mg, 1. After washing the filter cake with water 5 mL and drying under vacuum, compound was obtained. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2 or 3 substituents chosen from alkyl, alkenyl, alkynyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF 3amino, substituted amino, nitro, thiol, cyano, cycloalkyl, heterocyclyl, aryl, and heteroaryl.
Compounds that cannot penetrate the blood brain barrier, however, can still be effectively administered by an intravenous route. First Office Action mailed Jul. Such functions include, without limitation, stimulated superoxide release, stimulated exocytosis or degranulation, chemotactic migration, adhesion to vascular endothelium e. Intermediate compound 2 was prepared according to the procedures set forth in steps A-F below.
Compound 95 was prepared using the general procedure described above with respect to compound 14, but anthranilic acid was substituted for 2-aminomethylbenzoic acid and 3,5-difluoroaniline for aniline in step A, 2-tert-butoxycarbonylamino-propionic acid 2,5-dioxopyrrolidinyl ester was substituted for 2-benzyloxycarbonylaminobutyric acid 2,5-dioxo-pyrrolidinyl ester in step B, and the alternate procedure TFA deprotection was used in step C.
The process of claim 18wherein step b is performed at a temperature between 0 and 80 degrees Celsius. An alkyl group can be unsubstituted or optionally substituted with one or more substituents as described herein throughout.
Compound 87 is shown below.
In other embodiments, X orgzniczna Cl or Br. In certain embodiments, pharmaceutically acceptable salts of the compounds of formula 815141920and 21are disclosed.
Compounds that exhibit large therapeutic indices, i. For example, a kit can comprise a dosage form of a pharmaceutical composition and a package insert containing instructions for use of the composition in treatment of a medical condition.
Compound 91 was prepared using the general procedure described above with respect to compound organicznw, but 2-tert-butoxycarbonylamino-propionic acid roganiczna ester was substituted for 2-benzyloxycarbonylaminobutyric acid 2,5-dioxo-pyrrolidinyl ester in step B, the alternate procedure TFA deprotection was used in step C, and intermediate compound 1 was substituted for 6-bromopurine.
Elastase exocytosis is quantitated by modification of the procedure described by Ossanna et al. The effect compounds of the present invention on B cell proliferation response when they are stimulated through their cell surface IgM using anti-IgM antibody also was measured. The mixture was filtered to removed solvents, and the resulting filtrate was purified by HPLC to provide the product 41 as a white solid.
Unless otherwise constrained by preparafyka definition for the heteroaryl substituent, such heteroaryl groups can be optionally substituted with 1 to 5 substituents in some embodiments, 1, 2 or 3 substituents selected from the group consisting alkyl, alkenyl, alkynyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF 3amino, substituted amino, nitro, thiol, cyano, cycloalkyl, heterocyclyl, aryl, and heteroaryl.
Compound 68 is shown below. Parasharya and Parikh, J. In certain embodiments, the isotopically labeled compound is a compound of formula 6. A compound of formula 16 1.