34 results about "Camptothecin Analog" patented technology

The present invention provides novel conjugates of camptothecin and camptothecin analogs with a linker and an HSA-binding moiety. The novel conjugates are prodrug forms of the camptothecin or camptothecin analogs and can be used to treat mammalian cell proliferative diseases, such as cancer.

The novel C7-modified camptothecin analogs, and pharmaceutically-acceptable salts thereof, of the present invention: (i) possess potent antitumor activity (i.e., in nanomolar or subnanomolar concentrations) for inhibiting the growth of human and animal tumor cells in vitro; (ii) are potent inhibition of Topoisomerase I; (iii) lack of susceptibility to MDR / MRP drug resistance; (iv) require no metabolic drug activation: (v) lack glucuronidation of the A-ring or B-ring; (vi) reduce drug-binding affinity to plasma proteins; (vii) maintain lactone stability; (viii) maintain drug potency; and (ix) possess a low molecular weight (e.g., MW<600).

The novel C10-modified camptothecin analogs, and pharmaceutically-acceptable salts thereof, of the present invention: (i) possess potent antitumor activity (i.e., in nanomolar or subnanomolar concentrations) for inhibiting the growth of human and animal tumor cells in vitro; (ii) are potent inhibition of Topoisomerase I; (iii) lack of susceptibility to MDR / MRP drug resistance; (iv) require no metabolic drug activation: (v) lack glucuronidation of the A-ring or B-ring; (vi) reduce drug-binding affinity to plasma proteins; (vii) maintain lactone stability; (viii) maintain drug potency; and (ix) possess a low molecular weight (e.g., MW<600).

The present invention provides generally a compound having the following general formula (1):wherein R1 and R2 are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxyl group, an aryloxy group, an acyloxy group, a carbonyloxy group, a carbamoyloxy group, a halogen, a hydroxyl group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, —SRc, wherein, Rc is hydrogen, an acyl group, an alkyl group, or an aryl group, or R1 and R2 together form a group of the formula —O(CH2)nO— wherein n represents the integer 1 or 2; R3 is H, F, a halogen atom, a nitro group, an amino group, a hydroxyl group, or a cyano group; or R2 and R3 together form a group of the formula —O(CH2)nO— wherein n represents the integer 1 or 2; R4 is H, F, a C1-3 alkyl group, a C2-3 alkenyl group, a C2-3 alkynyl group, or a C1-3 alkoxyl group; R5 is a C1-10 alkyl group, or a propargyl group; and R6, R7 and R8 are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a —(CH2)NR9 group, wherein N is an integer within the range of 1 through 10 and R9 is a hydroxyl group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and pharmaceutically acceptable salts thereof.

This invention relates to antioxidant, neuroprotective and antineoplastic nanoparticles comprising a therapeutic agent on an amphiphilic spacer or an amphiphilic polymer. Methods of synthesizing the antioxidant derivatives of camptothecin and antioxidant derivatives of camptothecin analogs, NSAIDs and statins, spontaneous emulsification or nanoprecipitation thereof to produce antioxidant, neuroprotective and anti-neoplastic nanoparticles comprising a therapeutic agent on an amphiphilic spacer or an amphiphilic polymer and their use in treating cancerous diseases are also provided. A further aspect of this invention is the use of these neuroprotective and anti-neoplastic nanoparticles for the preparation of delivery devices of other pharmaceuticals and / or drugs.

(20 S )esters of camptothecin analogs are provided. The compounds are (20 S ) esters of an oxyalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.

The present invention discloses a process for efficient production of 2-amino-5-hydroxypropiophenone corresponding to the AB ring part of camptothecin (CPT) skeleton, which is a key intermediate useful for the total synthesis of camptothecin analogs including 7-Ethyl-10-hydroxy camptothecin and novel intermediates thereof.

A compound has the formulain racemic form, enantiomerically enriched form or enantiomerically pure form. R6 is preferably —Si(R8R9R10) or —(R7)Si(R8R9R10), wherein R7 is an alkylene group, an alkenylene group, or an alkynylene group; and R8, R9 and R10 are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a —(CH2)NR11 group, wherein N is an integer within the range of 1 through 10 and R11 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SRc or a nitro group. R1–R4 can be broadly substituted. R5 is preferably a C1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group. R13 is preferably H, F or —CH3. R16 is R16 is —C(O)Rf or H. The E-ring (the lactone ring) may be opened. A method of synthesis of compound (1) and intermediates in the synthesis thereof are provided.

The invention relates to the technical field of medicines and in particular relates to fluoro-substituted E cyclocamptothecin analogues and use thereof as a drug. The structure of the compounds is shown in a formula I; and the compounds exist in forms of raceme, diastereoisomer as well as any mixture of the forms or medical salts thereof. The compounds disclosed by the invention have the effect of restraining the activity of the topoisomerase I and can be used for preparing anti-tumor drugs and also can be used for preparing drugs for preventing virus and fungal infection.

The present invention discloses: (i) a novel, lactone-stable, ''flipped'' E-ring camptothecin, pharmaceutically-acceptable salts, and / or analogs thereof; (ii) methods of synthesis of said novel, lactone-stable, ''flipped'' E-ring camptothecin, pharmaceutically-acceptable salts, and / or analogs thereof; (iii) pharmaceutically-acceptable formulations comprising said novel, lactone-stable, ''flipped'' E-ring camptothecin, pharmaceutically-acceptable salts, and / or analogs thereof, and, optionally, one or more additional chemotherapeutic agents; (iv) methods of administration of said novel, lactone-stable, ''flipped'' E-ring camptothecin, pharmaceutically-acceptable salts, and / or analogs thereof, and, optionally, one or more additional chemotherapeutic agents, to subjects in need thereof; and (v) devices for the administration of said novel, lactone-stable, ''flipped'' E-ring camptothecin, pharmaceutically-acceptable salts, and / or analogs thereof, and, optionally, one or more chemotherapeutic agents, to subjects in need thereof.

The present invention provides generally a compound having the following general formula (1): wherein R1 and R2 are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxyl group, an aryloxy group, an acyloxy group, a carbonyloxy group, a carbamoyloxy group, a halogen, a hydroxyl group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, —SRc, wherein, Rc is hydrogen, an acyl group, an alkyl group, or an aryl group, or R1 and R2 together form a group of the formula —O(CH2)nO— wherein n represents the integer 1 or 2; R3 is H, F, a halogen atom, a nitro group, an amino group, a hydroxyl group, or a cyano group; or R2 and R3 together form a group of the formula —O(CH2)nO— wherein n represents the integer 1 or 2; R4 is H, F, a C1-3 alkyl group, a C2-3 alkenyl group, a C2-3 alkynyl group, or a C1-3 alkoxyl group; R5 is a C1-10 alkyl group, or a propargyl group; and R6, R7 and R8 are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a —(CH2)NR9 group, wherein N is an integer within the range of 1 through 10 and R9 is a hydroxyl group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and pharmaceutically acceptable salts thereof.

The novel C10-modified camptothecin analogs, and pharmaceutically-acceptable salts thereof, of the present invention: (i) possess potent antitumor activity (i.e., in nanomolar or subnanomolar concentrations) for inhibiting the growth of human and animal tumor cells in vitro; (ii) are potent inhibition of Topoisomerase I; (iii) lack of susceptibility to MDR / MRP drug resistance; (iv) require no metabolic drug activation: (v) lack glucuronidation of the A-ring or B-ring; (vi) reduce drug-binding affinity to plasma proteins; (vii) maintain lactone stability; (viii) maintain drug potency; and (ix) possess a low molecular weight (e.g., MW<600).

A compound and a method of synthesizing a compound having general formula (1): wherein R<1> and R<2> are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxy group, an aryloxy group, an acyloxy group, -OC(O)OR, wherein R is an alkyl group, a carbamoyloxy group, a halogen, a hydroxy group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, -SR, wherein R is hydrogen, an acyl group, an alkyl group, or an aryl group, or R<1> and R<2> together form a group of the formula -O(CH2)nO- wherein n represents the integer 1 or 2; R<3> is H, F, a halogen atom, a nitro group, an amino group, a hydroxy group, or a cyano group; or R<2> and R<3> together form a group of the formula -O(CH2)n O- wherein n represents the integer 1 or 2; R<4> is H, a trialkylsilyl group, F, a C1-3 alkyl group, a C2-3 alkenyl group, a C2-3 alkynyl group, or a C1-3 alkoxy group; R<5> is a C1-10 alkyl group, an allyl group, a benzyl group or a propargyl group; and R<6>, R<7> and R<8> are independently a C1-10 alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a -(CH2)NR<9> group, wherein N is an integer within the range of 1 through 10 and R<9> is a hydroxy group, alkoxy group, an amino group, alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and R<11> is an alkylene group or an alkenylene group, and pharmaceutically acceptable salts thereof.

The present invention relates to a process for preparation of 2-Amino-5-hydroxy propiophenone, a key intermediate for the synthesis of camptothecin analogs including 7-Ethyl-10-hydroxycamptothecin (SN-38).

(20 S )esters of camptothecin analogs are provided. The compounds are (20 S ) esters of an oxyalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.