Nitrosated and nitrosylated taxanes, compositions and methods of use
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/337
C07D-305/14
출원번호
US-0682923
(2003-10-14)
발명자
/ 주소
Garvey, David S.
Letts, L. Gordon
Lin, Chia-En
Richardson, Stewart K.
Wang, Tiansheng
출원인 / 주소
NitroMed, Inc.
대리인 / 주소
Wilmer Cutler Pickering Hale and Dorr LLP
인용정보
피인용 횟수 :
9인용 특허 :
54
초록▼
The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-deriv
The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The present invention also provides novel compositions comprising at least one taxane and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The compounds and compositions of the present invention can also be bound to a matrix. The present invention also provides methods for treating or preventing cardiovascular diseases and disorders, autoimmune diseases, pathological conditions resulting from abnormal cell proliferation, polycystic kidney disease, inflammatory disease, preserving organs and/or tissues or to inhibit wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis, by administering nitrosated and/or nitrosylated taxane or parent taxanes in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.
대표청구항▼
1. A composition comprising at least one compound selected from the group consisting of 15-((3S,2R)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoyloxy) (2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0&
1. A composition comprising at least one compound selected from the group consisting of 15-((3S,2R)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoyloxy) (2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0<4,7>)heptadec-13-en-9-yl 3-methyl-3-(nitrosothio)butanoate; (1S,2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1,9-dihydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0<4,7>) heptadec-13-en-15-yl(3S,2R)-2-(2-({N-(2-methyl-2-(nitrosothio)propyl) carbamoyl}methoxy)acetyloxy)-3-phenyl-3-(phenylcarbonylamino)propanoate; 9-(2-({((2R)-2,3-bis(nitrooxy)propyl)oxycarbonyl}methoxy)acetyloxy)(1S,2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0<4,7>)heptadec-13-en-15-yl 2-(2-({((2R)-2,3-bis(nitrooxy)propyl)oxycarbonyl}methoxy)acetyloxy)(3S,2R)-3-phenyl-3-(phenylcarbonylamino)propanoate; (1S,2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-9-{2-(({2,2-bis((nitrooxy)methyl)-3-(nitrooxy)propyl}oxycarbonyl)methoxy)acetyloxy}-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo (11.3.1.0<3,10>0.0<4,7>)heptadec-13-en-15-yl(3S,2R)-2-{2-(({2,2-bis((nitrooxy)methyl)-3-(nitrooxy)propyl}oxycarbonyl)methoxy)acetyloxy}-3-phenyl-3-(phenylcarbonylamino)propanoate, or a pharmaceutically acceptable salt thereof, and at least one compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor or is a substrate for nitric oxide synthase or a pharmaceutically acceptable salt thereof.2. A composition of claim 1 further comprising a pharmaceutically acceptable carrier.3. The composition of claim 1, wherein the at least one compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor or is a substrate for nitric oxide synthase is an S-nitrosothiol.4. The composition of claim 3, wherein the S-nitrosothiol is S-nitroso-N-acetylcysteine, S-nitroso-captopril, S-nitroso-N-acetylpenicillamine, S-nitroso-homocysteine, S-nitroso-cysteine or S-nitroso-glutathione.5. The composition of claim 3, wherein the S-nitrosothiol is:(i) HS(C(Re)(Rf))mSNO; (ii) ONS(C(Re)(Rf))mRe; and (iii) H2N?CH(CO2H)?(CH2)m?C(O)NH?CH(CH2SNO)?C(O)NH?CH2?CO2H; wherein m is an integer from 2 to 20; Re and Rf are each independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, an alkylcycloalkyl, an alkylheterocyclic ring, an alkoxy, a haloalkoxy, an amino, an alkylamino, a dialkylamino, an arylamino, a diarylamino, an alkylarylamino, an alkoxyhaloalkyl, a haloalkoxy, a sulfonic acid, a sulfonic ester, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cycloalkylthio, a cycloalkenyl, a cyano, an aminoalkyl, an aminoaryl, an aryl, an alkylaryl, a carboxamido, a alkylcarboxamido, an arylcarboxamido, an amidyl, a carboxyl, a carbamoyl, a carbamate, an alkylcarboxylic acid, an arylcarboxylic acid, an alkylcarbonyl, an arylcarbonyl, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a sulfonic ester, a urea, a phosphoryl, a nitro, Wh, -T-Q, or ?(C(Re)(Rf))k, or Re and Rf taken together with the carbons to which they are attached form a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group; Q is ?NO or ?NO2; and T is independently a covalent bond, a carbonyl, an oxygen, ?S(O)o? or ?N(Ra)Ri, wherein o is an integer from 0 to 2, Ra is a lone pair of electrons, a hydrogen or an alkyl group; Ri is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an aryl carboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an arylsulfinyl, an arylsulfonyl, a sulfonamido, a carboxamido, a carboxylic ester, an amino alkyl, an amino aryl, ?CH2?C(T-Q)(Re)(Rf), or ?(N2O2?).M+, wherein M+ is an organic or inorganic cation; with the proviso that when Ri is ?CH2?C(T-Q)(Re)(Rf) or ?(N2O2?).M+; then “-T-Q” can be a hydrogen, an alkyl group, an alkoxyalkyl group, an aminoalkyl group, a hydroxy group or an aryl group. 6. The composition of claim 1, wherein the at least one compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase is:(i) a compound that comprises at least one ON?O?, ON?N? or ON?C? group; (ii) a compound that comprises at least one O2N?O?, O2N?N?, O2N?S? or ?O2N?C? group; (iii) a N-oxo-N-nitrosoamine having the formula: R1R2N?N(O-M+)?NO, wherein R1 and R2 are each independently a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group, and M+ is an organic or inorganic cation. 7. The composition of claim 6, wherein the compound comprising at least one ON?O?, ON?N? or ON?C? group is an ON?O-polypeptide, an ON?N-polypepetide, an ON?C-polypeptide, an ON?O-amino acid, an ON?N-amino acid, an ON?C-amino acid, an ON?O-sugar, an ON?N-sugar, an ON?C-sugar, an ON?O-oligonucleotide, an ON?N-oligonucleotide, an ON?C-oligonucleotide, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON?O-hydrocarbon, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON?N-hydrocarbon, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON?C-hydrocarbon, an ON?O-heterocyclic compound, an ON?N-heterocyclic compound or a ON?C-heterocyclic compound.8. The composition of claim 6, wherein compound comprising at least one O2N?O?, O2N?N?, O2N?S? or O2N?C? group is an O2N?O-polypeptide, an O2N?N-polypeptide, an O2N?S-polypeptide, an O2N?C-polypeptide, an O2N?O-amino acid, O2N?N-amino acid, O2N?S-amino acid, an O2N?C-amino acid, an O2N?O-sugar, an O2N?N-sugar, O2N?S-sugar, an O2N?C-sugar, an O2N?O-oligonucleotide, an O2N?N-oligonucleotide, an O2N?S-oligonucleotide, an O2N?C-oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N?O-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N?N-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N?S-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N?C-hydrocarbon, an O2N?O-heterocyclic compound, an O2N?N-heterocyclic compound, an O2N?S-heterocyclic compound or an O2N?C-heterocyclic compound.9. The composition of claim 1, wherein the at least one compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase, is L-arginine, L-homoarginine, N-hydroxy-L-arginine, nitrosated L-arginine, nitrosylated L-arginine, nitrosated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, citrulline, ornithine, glutamine, lysine, polypeptides comprising at least one of these amino acids or inhibitors of the enzyme arginase.10. The composition of claim 1, wherein the at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase is a NONOate.11. The composition of claim 2, further comprising at least one therapeutic agent.12. The composition of claim 11, wherein the therapeutic agent is a antithrombogenic agent, a thrombolytic agent, a fibrinolytic agent, a vasospasm inhibitor, a potassium channel activator, a calcium channel blocker, an antihypertensive agent, an antimicrobial agent, an antibiotic, an antiplatelet agent, an antimitotic agent, an antiproliferative agent, a microtubule inhibitor, an antisecretory agent, a remodelling inhibitor, an antisense nucleotide, an anti-cancer chemotherapeutic agent, a steroid, a non-steroidal antiinflammatory agent, a selective COX-2 inhibitor, an immunosuppressive agent, a growth factor antagonist or antibody, a dopamine agonist, a radiotherapeutic agent, a heavy metal functioning as a radioplaque agent, a biologic agent, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a renin inhibitor, a free radical scavenger, an iron chelator, an antioxidant, a sex hormone, an antipolymerase, an antiviral agent, a photodynamic therapy agent, an antibody targeted therapy agent, a gene therapy agent, or a mixture thereof.13. A method for treating or preventing a cardiovascular disease or disorder in a patient in need thereof comprising administering a therapeutically effective amount of the composition of claim 2 or 11.14. The method of claim 13, wherein the cardiovascular disease or disorder is restenosis, atherosclerosis, atherogenesis, angina, ischemic disease, congestive heart failure or pulmonary edema associated with acute myocardial infarction, atherosclerosis, thrombosis, controlling blood pressure in hypertension, platelet adhesion, platelet aggregation, smooth muscle cell proliferation, vascular complications associated with the use of medical devices, wounds associated with the use of medical devices, myocardial infarction, pulmonary thromboembolism, cerebral thromboembolism, thrombophlebitis, thrombocytopenia or bleeding disorders.15. The method of claim 14, wherein the cardiovascular disease or disorder is restenosis or atherosclerosis.16. A method for treating or preventing an autoimmune disease, a pathological condition resulting from abnormal cell proliferation, polycyctic kidney disease, an inflammatory disease, for preserving an organ and/or a tissue or for inhibiting wound contraction in a patient in need thereof comprising administering a therapeutically effective amount of the composition of claim 2 or 11.17. The method of claim 16, wherein the pathological condition resulting from abnormal cell proliferation is a cancer, a Karposi's sarcoma, a cholangiocarcinoma, a choriocarcinoma, a neoblastoma, a Wilm's tumor, Hodgkin's disease, a melanoma, multiple myelomas, a chronic lymphocytic leukemia or an acute or chronic granulocytic lymphoma.18. The method of claim 16, wherein the inflammatory disease is rheumatoid arthritis, an inflammatory skin disease, restenosis, multiple sclerosis, a surgical adhesion, tuberculosis, a graft rejection, an inflammatory lung disease, an inflammatory bowel disease, an inflammatory disease that affects or causes obstruction of a body passageway, an inflammation of the eye, an inflammation of the nose, an inflammation of the throat or a neovascular diseases of the eye.19. The method of claim 13, wherein the composition is administered intravenously, orally, bucally, parenterally, by an inhalation spray, by topical application or transdermally.20. The method of claim 13, wherein the composition is administered via local administration.21. The method of claim 20, wherein the local administration of the compound is via a suture, a vascular implant, a stent, a heart valve, a drug pump, a drug delivery catheter, an infusion catheter, a drug delivery guidewire or an implantable medical device.22. A method for delivering nitric oxide to a targeted site in a patient in need thereof comprising administering the composition of claim 2 or 11 to the targeted site in the patient.23. The method of claim 22, wherein the composition provides sustained delivery of nitric oxide to the targeted sited in the patient.24. A composition comprising at least one compound selected from the group consisting of 15-((3S,2R)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoyloxy) (2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0<4,7>)heptadec-13-en-9-yl 3-methyl-3-(nitrosothio)butanoate; (1S,2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1,9-dihydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0<4,7>) heptadec-13-en-15-yl(3S,2R)-2-(2-({N-(2-methyl-2-(nitrosothio)propyl) carbamoyl}methoxy)acetyloxy)-3-phenyl-3-(phenylcarbonylamino)propanoate; 9-(2-({((2R)-2,3-bis(nitrooxy)propyl)oxycarbonyl}methoxy)acetyloxy)(1S,2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo(11.3.1.0<3,10>0.0<4,7>)heptadec-13-en-15-yl 2-(2-({((2R)-2,3-bis(nitrooxy)propyl)oxycarbonyl}methoxy)acetyloxy)(3S,2R)-3-phenyl-3-(phenylcarbonylamino)propanoate; (1S,2S,4S,9S,10S,15S,7R,12R)-4,12-diacetyloxy-9-{2-(({2,2-bis((nitrooxy)methyl)-3-(nitrooxy)propyl}oxycarbonyl)methoxy)acetyloxy}-1-hydroxy-10,14,17,17-tetramethyl-6-oxa-11-oxo-2-phenylcarbonyloxytetracyclo (11.3.1.0<3,10>0.0<4,7>)heptadec-13-en-15-yl(3S,2R)-2-{2-(({2,2-bis((nitrooxy)methyl)-3-(nitrooxy)propyl}oxycarbonyl)methoxy)acetyloxy}-3-phenyl-3-(phenylcarbonylamino)propanoate, or a pharmaceutically acceptable salt thereof, bound to a matrix, wherein the matrix is a natural polymer, a synthetic polymer, a natural fiber, a synthetic fiber, or a mixture thereof.25. The composition of claim 24, wherein the polymer is a polyolefin, a polyethylenimine, a polyethyleneimine derivative, a polyether, a polyanhydride, a polyhydroxybutyrate, a polyester, a polyamide, a polyurethane, a copolymer, a blocked polymer, a blocked coploymer, a biopolymer, a starburst dendrimer, or a mixture thereof.26. The composition of claim 24, further comprising at least one compound that is a compound that donates, transfers or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase, at least one therapeutic agent or a mixture thereof.27. A method for delivering nitric oxide to a targeted site in a patient in need thereof comprising administering the composition of claim 24 or 26 to the targeted site in the patient.28. The method of claim 27, wherein the composition provides sustained delivery of nitric oxide to the targeted sited in the patient.29. A medical device comprising the composition of claim 24 or 26.30. The medical device of claim 29, wherein the composition coats all or a portion of the surface of the medical device.31. The medical device of claim 29, wherein the composition forms all or part of the medical device.32. The medical device of claim 29, wherein the medical device is a balloon, a catheter tip, a stent, a catheter, a prosthetic heart valve, a synthetic vessel graft, an arteriovenous shunt, a heart valve, a suture, a vascular implant, a drug pump, a drug delivery catheter, plastic tubing, a dialysis bag, a lead, a pacemaker, an implantable pulse generator, an implantable cardiac defibrillator, a cardioverter defibrillator, a defibrillator, a spinal stimulator, a brain stimulator, a sacral nerve stimulator, a chemical sensor or a membrane surface.33. A method for preventing platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device comprising incorporating at least one composition of claim 24 or 26 or a pharmaceutically acceptable salt thereof, into or on the medical device.34. The method of claim 33, wherein the medical device is a balloon, a catheter tip, a stent, a catheter, a prosthetic heart valve, a synthetic vessel graft, an arteriovenous shunt, a heart valve, a suture, a vascular implant, a drug pump, a drug delivery catheter, plastic tubing, a dialysis bag, a lead, a pacemaker, an implantable pulse generator, an implantable cardiac defibrillator, a cardioverter defibrillator, a defibrillator, a spinal stimulator, a brain stimulator, a sacral nerve stimulator, a chemical sensor or a membrane surface.35. The method of claim 33, wherein the blood is a blood product or a blood component.36. A method for treating injured tissue in a patient in need thereof comprising administering at least one composition of claim 24 or 26 or a pharmaceutically acceptable salt thereof, to the site of the injured tissue in the patient.37. The method of claim 36, wherein the injured tissue is a blood vessel.38. The method of claim 36, wherein the compound is administered to the site of the injured tissue via at least one of a suture, a vascular implant, a stent, a heart valve, a drug pump or a drug delivery catheter.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (54)
Kelly Robert C. ; Skulnick Harvey I., .DELTA..sup.6,7 -taxols antineoplastic use and pharmaceutical compositions containing them.
Stella Valentino J. (Lawrence KS) Mathew Abraham E. (Lenexa KS), Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof.
Shapland James E. (Shoreview MN) Knudson Mark B. (Shoreview MN) Shimada Jin (Falcon Heights MN) Hildebrand Keith R. (Houlton WI), Drug delivery apparatus and method.
Mayhew Eric (Monmouth Junction NJ) Ali Shaukat (Monmouth Junction NJ) Janoff Andrew S. (Yardley PA), Hydrolysis-promoting hydrophobic taxane derivatives.
Cooke John P. ; Schwarzacher Sverin ; Lim Tai T.,SGX ; Yeung Alan C., Intramural delivery of nitric oxide enhancer for inhibiting lesion formation after vascular injury.
Cooke John P. ; Schwarzacher Sverin ; Lim Tai T.,SGX ; Yeung Alan C., Intramural delivery of nitric oxide enhancer for inhibiting lesion formation after vascular injury.
Rosen Gerald M. ; Herzog ; Jr. William R. ; Pou Sovitj, Medical device with a surface adapted for exposure to a blood stream which is coated with a polymer containing a nitrosy.
Hawiger Jack J. (Chestnut Hill MA) Timmons Sheila (Boston MA) Kloczewiak Marek (Jamaica Plain MA), Method of producing biologically active molecules having extended life time.
Kinsella James L. (Baltimore MD) Sollott Steven J. (Baltimore MD), Method of treating atherosclerosis or restenosis using microtubule stabilizing agent.
Haugwitz Rudiger D. (Bethesda MD) Zalkow Leon (Atlanta GA) Glinski Jan (Ridgefield CT) Suffness Mathew (Silver Spring MD) Deutsch Howard M. (Atlanta GA) Narayanan Venkatachala (Gaithersburg MD), Method of treating cancers sensitive to treatment with water soluble derivatives of taxol.
Stanley Theodore H. (Salt Lake City UT) Hague Brian (West Valley City UT), Methods and compositions for noninvasive dose-to-effect administration of drugs with cardiovascular or renal vascular ac.
Rosen Gerald M. (Lutherville MD) Herzog ; Jr. William R. (Baltimore MD) Pou Sovitj (Baltimore MD), Nitric oxide-releasing nitroso compositions and methods and intravascular devices for using them to prevent restenosis.
de Bont Hendricus B. A.,NLX ; Leenders Ruben G. G.,NLX ; Scheeren Johan W.,NLX ; Haisma Hidde J.,NLX ; de Vos Dick,NLX, Paclitaxel prodrugs, method for preparation as well as their use in selective chemotherapy.
Golik Jerzy (Southington CT) Vyas Dolatrai (Madison CT) Wright John J. (Guilford CT) Wong Henry (Durham CT) Kadow John F. (Wallingford CT) Thottathil John K. (Robbinsville NJ) Li Wen-Sen (Marlboro NJ, Phosphonooxymethyl ethers of taxane derivatives.
Holton Robert A. (Tallahassee FL), Preparation of substituted isoserine esters using metal alkoxides and b
상세보기
Holton Robert A. (Tallahassee FL) Kim Seokchan (Tallahassee FL), Process for the preparation of baccatin III analogs bearing new C2 and C4 functional groups.
Zheng Qun Y. (Superior CO) Darbie Lynn G. (Boulder CO) Murray Christopher K. (Boulder CO), Selective process for the deacylation and deacetylation of taxol and taxanes.
Swindell Charles S. ; Krauss Nancy, Syntheses of taxol, taxol analogs and their intermediates with variable A-ring side chain structures and compositions thereof.
Swindell Charles S. ; Krauss Nancy, Synthesis of taxol, taxol analogs and their intermediates with variable A-ring side chain structures and compositions thereof.
Kunz Lawrence L. ; Klein Richard A. ; Reno John M. ; Grainger David J.,GB2 ; Metcalfe James C.,GB2 ; Weissberg Peter L.,GB2 ; Anderson Peter G., Therapeutic inhibitor of vascular smooth muscle cells.
Cooke John P. (Palo Alto CA) Dzau Victor J. (Los Altos Hills CA) Gibbons Gary H. (Palo Alto CA), Treatment of vascular degenerative diseases by modulation of endogenous nitric oxide production of activity.
Cooke John P. ; Dzau Victor J. ; Gibbons Gary H., Treatment of vascular degenerative diseases by modulation of endogenous nitric oxide production or activity.
Demopulos Gregory A. ; Pierce Pamela A. ; Herz Jeffrey M., Vascular irrigation solution and method for inhibition of pain, inflammation, spasm and restenosis.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.