Nilotinib drug patented

With the big hit of the movie I'm not a drug god, one of the drugs for the treatment of leukemiaGleevec is well known, and nilotinib, another drug for leukemia (Nilotinib), alias nilotinib is an antineoplastic drug, which is mainly used in clinical treatment of chronic myelogenous leukemia resistant to Gleevec (imatinib).

 The drug2009Year7Month by Novartis in China's import listing, trade name.Dahina®, the approved indication is a second-line treatment, I .e., for prior treatment (includingImatinib) Drug-resistant or intolerant Philadelphia chromosome-positive chronic myeloid white bloodThe disease (Ph CML) Adult patients in chronic or accelerated phase.

Nilotinib is improved from the molecular structure of imatinibBCR-ABLKinase activity has a stronger selectivity, the inhibition of tyrosine kinase is stronger than imatinib30fold, can inhibit resistance to imatinibBCR-ABLKinase activity of the mutant. It also suppressesKITandPDGFRkinase activity.

Taken twice daily, nilotinib can act through targetedBcr-Ablprotein to inhibit the production of cancer cells containing abnormal chromosomes.

NilotinibInChina's patent layout is as follows:

1.Tyrosine Kinase Inhibitors, Patent No.CN200710107748.1Claim1As follows:

1.Type(I)compounds therein

R1represents hydrogen, lower alkyl, lower alkoxy-Lower alkyl, acyloxy-Lower alkyl, carboxyl-Lower alkyl, lower alkoxycarbonyl-Lower alkyl or phenyl-lower alkyl;

R2represents hydrogen, optionally by one or more identical or different groupsR3substituted lower alkyl,Cycloalkyl, benzocycloalkyl, heterocyclyl, aryl or mono containing zero, 1. two or three ring nitrogen atoms and zero or one epoxy atom and zero or one ring sulfur atom-or two-ring heteroaryl, these groups are in each case unsubstituted or mono-or more-superseded;

R3Represents hydroxyl, lower alkoxy, acyloxy, carboxyl, lower alkoxycarbonyl, carbamoyl,N-Single-orN,N-2-Substituted carbamoyl, amino, mono.-or two-Substituted amino, cycloalkyl, heterocyclyl, aryl or mono containing zero, 1. two or three ring nitrogen atoms and zero or one epoxy atom and zero or one ring sulfur atom-or two-ring heteroaryl, these groups are in each case unsubstituted or mono-or more-superseded; or in whichR1andR2Together represents an alkylene group having 4. to five or six carbon atoms, which is optionally represented by lower alkyl, cycloalkyl, heterocyclyl, phenyl, hydroxy, lower alkoxy, amino, mono--or two-Substituted amino, oxo, pyridyl, pyrazinyl or pyrimidinyl mono-or two-substituted; a benzenealkylene group having four or five carbon atoms in the alkylene group; an oxaalkylene group having one oxygen and three or four carbon atoms; or an azaalkylene group having one nitrogen and three or four carbon atoms,where nitrogen is unsubstituted or substituted by lower alkyl, phenyl-Lower alkyl, lower alkoxycarbonyl-Lower alkyl, carboxyl-Lower alkyl, carbamoyl-lower alkyl,N-Single-orN,N-2-substituted carbamoyl-Lower alkyl, cycloalkyl, lower alkoxycarbonyl, carbony,phenyl, substituted phenyl, pyridyl, pyrimidinyl or pyrazinyl substituted;

R4represents hydrogen, lower alkyl or halogen;and the compound'sN-oxides or pharmaceutically acceptable salts.

2. Tyrosine Kinase Inhibitors, Application No.CN03818728.0Claim1As follows:

1.TypeIcompounds,

Among them form

R1represents hydrogen, lower alkyl, lower alkoxy-Lower alkyl or benzyl;

R2represents phenyl substituted by one or two substituents selected from lower alkyl, trifluoro-Lower alkyl, hydroxyl-Lower alkyl, amino-Lower Alkyl, Lower Alkyl Amino-Lower alkyl, by-lower alkyl amino-lower alkyl,N-Cyclohexyl-N-lower alkyl amino-Lower alkyl, lower alkoxycarbonyl-1-piperidinyl-lower alkyl,N-lower alkyl-1-Piperazinyl-Lower alkyl, lower alkoxycarbonyl-Lower alkyl, hydroxy, lower alkoxy, trifluorine-lower alkoxy,1H-Imidazolyl-Lower alkoxy, alkanoyloxy lower, benzoyloxy, carboxy, alkoxycarbonyl lower, carbamoyl, alkylcarbamoyl lower, amino, alkanoylamino lower, benzoylamino, alkyl lower, hydroxy-Lower alkyl or lower alkoxy-lower alkyl mono-or two-substituted amino,1H-Imidazolyl, lower alkyl-1H-Imidazolyl,1-Pyrrolidinyl,1-piperidinyl,1-Piperazinyl,N-lower alkyl-1-Piperazinyl,4-morpholinyl, sulfamoyl, lower alkylsulfonyl, phenyl, pyridyl, halogen or benzoyl;

R4represents hydrogen or lower alkyl;

or itsN-oxides or pharmaceutically acceptable salts.

These two patents, the first has been rejected, the secondExpiry dateFor:2023-07-04In the second, compared to the first patent, the claims are not right.R3Limits. Reading the patent text shows that the compound formula does not involveR3Group.

It is reported that the drug has entered the medical insurance in Tibet, Jiangxi and Jiangsu.