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07/12/07 - USPTO Class 514 |  52 views | #20070161666 | Prev - Next | About this Page  514 rss/xml feed  monitor keywords

Pyrrolo[2,3-d]pyrimidine compounds

USPTO Application #: 20070161666
Title: Pyrrolo[2,3-d]pyrimidine compounds
Abstract: wherein R1, R2 and R3 are as defined above, useful as inhibitors of protein kinases, such as the enzyme Janus Kinase 3. A compound of the formula (end of abstract)



Agent: Pfizer Inc. - Groton, CT, US
Inventors: Todd A. Blumenkopf, Mark E. Flanagan, Michael J. Munchhof
USPTO Applicaton #: 20070161666 - Class: 514265100 (USPTO)

Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered Consisting Of Two Nitrogens And Four Carbon Atoms (e.g., Pyridazines, Etc.), 1,4-diazine As One Of The Cyclos, Polycyclo Ring System Having 1,3-diazine As One Of The Cyclos, A Ring Nitrogen Is Shared By The Two Cyclos Of The Bicyclo Ring System (e.g., Pyrrolo [1,2-a]pyrimidine, Imidazo[1,2-a]pyrimidine, Etc.),

Pyrrolo[2,3-d]pyrimidine compounds description/claims


The Patent Description & Claims data below is from USPTO Patent Application 20070161666, Pyrrolo[2,3-d]pyrimidine compounds.

Brief Patent Description - Full Patent Description - Patent Application Claims
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CROSS-REFERENCE TO RELATED APPLICATION

[0001] This non-provisional application is based upon and claims priority from U.S. provisional patent application No. 60/214,287, filed Jun. 26, 2000.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to pyrrolo[2,3-d]pyrimidine compounds which are inhibitors of protein kinases, such as the enzyme Janus Kinase 3 (hereinafter also referred to as JAK3) and as such are useful therapy as immunosuppressive agents for organ transplants, xeno transplantation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other indications where immunosuppression would be desirable.

[0003] This invention also relates to a method of using such compounds in the treatment of the above indications in mammals, especially humans, and the pharmaceutical compositions useful therefor.

[0004] JAK3 is a member of the Janus family of protein kinases. Although the other members of this family are expressed by essentially all tissues, JAK3 expression is limited to hematopoetic cells. This is consistent with its essential role in signaling through the receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 by non-covalent association of JAK3 with the gamma chain common to these multichain receptors. XSCID patient populations have been identified with severely reduced levels of JAK3 protein or with genetic defects to the common gamma chain, suggesting that immunosuppression should result from blocking signaling through the JAK3 pathway. Animal studies have suggested that JAK3 not only plays a critical role in B and T lymphocyte maturation, but that JAK3 is constitutively required to maintain T cell function. Modulation of immune activity through this novel mechanism can prove useful in the treatment of T cell proliferative disorders such as transplant rejection and autoimmune diseases.

SUMMARY OF THE INVENTION

[0005] The present invention relates to a compound of the formula or the pharmaceutically acceptable salt thereof; wherein

[0006] R.sup.1 is a group of the formula wherein y is 0, 1 or 2;

[0007] R.sup.4 is selected from the group consisting of hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, nitro, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl or (C.sub.1-C.sub.6)acylamino; or R.sup.4 is (C.sub.3-C.sub.10)cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino;

[0008] R.sup.5 is (C.sub.2-C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five groups consisting of carboxy, cyano, amino, deuterium, hydroxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m(C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.mR.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; and a group of the formula wherein a is 0, 1, 2, 3 or 4; [0009] b, c, e, f and g are each independently 0 or 1; [0010] d is 0, 1, 2, or 3; [0011] X is S(O).sub.n wherein n is 0, 1 or 2; oxygen, carbonyl or --C(.dbd.N-cyano)-; [0012] Y is S(O).sub.n wherein n is 0, 1 or 2; or carbonyl; and [0013] Z is carbonyl, C(O)O--, C(O)NR-- wherein R is hydrogen or (C.sub.1-C.sub.6)alkyl; or Z is S(O).sub.n wherein n is 0, 1 or 2;

[0014] R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each independently selected from the group consisting of hydrogen or (C.sub.1-C.sub.6)alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino;

[0015] R.sup.12 is (C.sub.8-C.sub.10)aryl, (C.sub.2-C.sub.9)heteroaryl, (C.sub.3-C.sub.10)cycloalkyl or (C.sub.2-C.sub.9)heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups are optionally substituted by one to four groups consisting of hydrogen, deuterium, amino, halo, oxo, hydroxy, nitro, carboxy, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, (C.sub.3-C.sub.10)cycloalkyl, (C.sub.1-C.sub.8)alkyl-CO--NH--, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, carboxy(C.sub.1-C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.8-C.sub.10)aryl, amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.8-C.sub.10)aryl(C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)alkyl, hydroxy, (C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonyl, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5-C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.8-C.sub.10)arylamino-CO--NH--, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylcyano, (C.sub.1-C.sub.6)alkylcarboxy(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylcarboxy, sulfonylamino, aminosulfonyl, sulfonylamino(C.sub.1-C.sub.6)alkyl, sulfonylaminocarboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.6-C.sub.10)arylsulfonylamino, (C.sub.6-C.sub.10)arylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.10)cycloalkyl, (C.sub.3-C.sub.10)cycloalkoxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.8-C.sub.10)arylamino, (C.sub.1-C.sub.6)alkylthio, (C.sub.8-C.sub.10)arylthio, (C.sub.1-C.sub.6)alkylsulfinyl, (C.sub.6-C.sub.10)arylsulfinyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl or (C.sub.6-C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups which are optionally substituted on R.sup.12 may be further substituted by one-to three groups consisting of halo, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-CO--NH--, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, carboxy(C.sub.1-C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.8-C.sub.10)aryl, amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.8-C.sub.10)aryl(C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)alkyl, hydroxy, (C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonyl, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5-C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.8-C.sub.10)arylamino-CO--NH--, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.8-C.sub.10)arylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.8-C.sub.10)arylsulfonyl, (C.sub.6-C.sub.10)arylsulfonylamino, (C.sub.8-C.sub.10)arylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroaryl and (C.sub.2-C.sub.9)heterocycloalkyl;

[0016] R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, (C.sub.3-C.sub.10)cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C.sub.1-C.sub.6)alkylthio, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl, (C.sub.3-C.sub.9)cycloalkyl or (C.sub.8-C.sub.10)aryl; or R.sup.2 and R.sup.3 are each independently (C.sub.3-C.sub.10)cycloalkyl, (C.sub.3-C.sub.10)cycloalkoxy. (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.8-C.sub.10)arylamino, (C.sub.1-C.sub.6)alkylthio, (C.sub.8-C.sub.10)arylthio, (C.sub.1-C.sub.6)alkylsulfinyl, (C.sub.8-C.sub.10)arylsulfinyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.8-C.sub.10)arylsulfonyl, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyamino-CO--, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl or (C.sub.8-C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-CO--NH--, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, carboxy(C.sub.1-C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1-C.sub.6)alkoxy. (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.8-C.sub.10)aryl, amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.8-C.sub.10)aryl(C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)alkyl, hydroxy, (C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonyl, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5-C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.8-C.sub.10)arylamino-CO--NH--, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.8)alkyl).sub.2amino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.8-C.sub.10)arylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.8-C.sub.10)arylsulfonyl, (C.sub.8-C.sub.10)arylsulfonylamino, (C.sub.8-C.sub.10)arylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroaryl or (C.sub.2-C.sub.9)heterocycloalkyl;

[0017] with the proviso that R.sup.5 must be substituted by the group of formula II.

[0018] The present invention also relates to the pharmaceutically acceptable acid addition salts of compounds of the formula I. The acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned base compounds of this invention are those which form non-toxic add addition salts, I.e., salts containing pharmacologically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [i.e., 1,1'-methylene-bis-(2-hydroxy-3-naphthoate)]salts.

[0019] The invention also relates to base addition salts of formula I. The chemical bases that may be used as reagents to prepare pharmaceutically acceptable base salts of those compounds of formula I that are acidic in nature are those that form non-toxic base salts with such compounds. Such non-toxic base salts include, but are not limited to those derived from such pharmacologically acceptable cations such as alkali metal cations (e.g., potassium and sodium) and alkaline earth metal cations (e.g., calcium and magnesium), ammonium or water-soluble amine addition salts such as N-methylglucamine-(meglumine), and the lower alkanolammonium and other base salts of pharmaceutically acceptable organic amines.

[0020] The term "Oxone.RTM." is a name of a monopersulfate compound used in this invention, having the formula 2KHSO.sub.5.KHSO.sub.4.K.sub.2SO.sub.4, and sold by Aldrich Chemical Company, P.O. Box 2060, Milwaukee, Wis. 53201, USA.

[0021] The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight or branched moieties or combinations thereof.

[0022] The term "alkoxy", as used herein, includes O-alkyl groups wherein "alkyl" is defined above.

[0023] The term "halo", as used herein, unless otherwise indicated, includes fluoro, chloro, bromo or iodo.

[0024] The compounds of this invention may contain double bonds. When such bonds are present, the compounds of the invention exist as cis and trans configurations and as mixtures thereof.

[0025] Unless otherwise indicated, the alkyl and alkenyl groups referred to herein, as well as the alkyl moieties of other groups referred to herein (e.g., alkoxy), may be linear or branched, and they may also be cyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl) or be linear or branched and contain cyclic moieties. Unless otherwise indicated, halogen includes fluorine, chlorine, bromine, and iodine.

[0026] (C.sub.2-C.sub.9)Heterocycloalkyl when used herein refers to pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, aziridinyl, oxiranyl, methylenedioxyl, chromenyl, isoxazolidinyl, 1,3-oxazolidin-3-yl, isothiazolidinyl, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl, piperidinyl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, morpholinyl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, tetrahydroazepinyl, piperazinyl, chromanyl, etc. One of ordinary skill in the art will understand that the connection of said (C.sub.2-C.sub.9)heterocycloalkyl rings is through a carbon or a sp.sup.3 hybridized nitrogen heteroatom.

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Previous Patent Application:
Process for preparing inhibitors of nucleoside metabolism
Next Patent Application:
Di-ester prodrugs of camptothecin, process for their preparation and their therapeutical applications
Industry Class:
Drug, bio-affecting and body treating compositions

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