- Process for preparing cyclophosphamide, intermediates, and monohydrate thereof
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The present disclosure provides a process for preparing cyclophosphamide, intermediate, and the monohydrate thereof.
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Page/Page column 4; 5
(2019/11/28)
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- Synthetic method for cyclophosphoramide
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The invention provides a synthetic method for cyclophosphoramide. According to the synthetic method, phosphorus oxychloride is slowly added into a mixed solution of dichloroethane, polyphosphoric acidand acetic anhydride, 3-amino propyl alcohol is dropwise added so as to prepare 2-chloro-2-oxo-[1.3.2] oxygen-nitrogen-phosphorus heterocyclic hexane; and dichloroethane and a 5a molecular sieve areadded, ammonia gas is introduced, heating is carried out at 4 atm to reach 120 DEG C, reaction is carried out for 2-2.5 hours, and treatment is carried out so as to obtain the cyclophosphoramide. Themethod has the advantages that the reaction conditions are relatively mild, and the yield and the content are high.
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Paragraph 0026; 0029; 0030; 0033-0037
(2019/04/11)
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- Cyclophosphamide synthetic method
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The invention provides a cyclophosphamide synthetic method. The cyclophosphamide synthetic method is characterized by comprising the following steps: adding dichloroethane into a reaction flask; slowly adding phosphorus oxychloride; starting to drip a 3-amino propanol and triethylamine mixed solvent; performing a reaction after finish of dripping to prepare a 2-chloro-2-oxo-[1,3,2] oxaphosphorinane solution; then transferring the 2-chloro-2-oxo-[1,3,2] oxaphosphorinane solution into the pressure reaction flask; adding triethylamine; controlling the temperature; continuously pumping into ammonia gas; keeping a certain pressure for a reaction; separating an organic phase from a reaction liquid; performing vacuum concentration on the organic phase till the organic phase is dry; adding a solvent; and performing crystallization to obtain cyclophosphamide. The cyclophosphamide synthetic method is high in yield, less in byproduct, simple in step and convenient to operate and facilitates industrial production.
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Paragraph 0030; 0031; 0032
(2018/06/15)
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- Solvent-Free Process for the Preparation of Cyclophosphamide
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This invention discloses a solvent-free process for the preparation of cyclophosphamide. According to this invention, there is no solvent used during the reaction step for preparing cyclophosphamide, so that the total volume of the reaction for preparing cyclophosphamide can be reduced and the manufacture of cyclophosphamide can become more efficient. Furthermore, the above solvent-free process for the preparation of cyclophosphamide is more simply operated, more economic, and more environmental friendly than the preparation of cyclophosphamide in the prior art.
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Paragraph 0039; 0040; 0041; 0042
(2014/03/25)
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- Antitumor activities of some new 1,3,2-oxaza- and 1,3,2-diazaphosphorinanes against K562, MDA-MB-231, and HepG2 cells
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New X-substituted 1,3,2-oxazaphosphorinanes, where X = NHC 6H5 (1), NHC6H4S(O) 2NH2-4 (2), NHC6 H4OCH3-4 (3), NHC6H4NO2-4 (4), OC6H 4CH3-4 (5), NHC(O)C6H4NO 2-4 (6), plus one X-substituted 1,3,2-diazaphosphorinane, where X = NHC6H4S(O)2NH2-4 (7), were synthesized and characterized by NMR, IR spectroscopy, and elemental analysis. The antitumor activities of these compounds, cyclophosphamide (CP), sulfanilamide (SA), and two X-substituted 5,5-dimethyl-1,3,2- diazaphosphorinanes, where X = NHC6H5 (8) OC 6H4CH3-4 (9), were evaluated by cell culture on K562, MDA-MB-231, and HepG2 cell lines using MTT cell proliferation assay. The IC50 values for CP and compounds 1-9 were in the range of 0.06 μM (for inhibition of HepG2 cells by compound 3) to 3.17 μM (for inhibition of HepG2 cells by compound 8). It was found that compounds 2 and 7 containing sulfonamide substituent and also SA itself are the best candidates for antitumor activity very close to CP. Springer Science+Business Media, LLC 2011.
- Gholivand, Khodayar,Ghaziani, Fatemeh,Shariatinia, Zahra,Dorosti, Nilufar,Mirshahi, Manouchehr,Sarikhani, Sina
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p. 2185 - 2195
(2012/11/07)
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- THERAPEUTIC FOR HEPATIC CANCER
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A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
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- Therapeutic use of at least one botulinum neurotoxin in the treatment of pain induced by at least one anti-neoplastic agent
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The present invention relates to a method of treating or preventing pain or pains induced by an anti-neoplastic agent, comprising the step of administering an effective amount of at least one botulinum neurotoxin to a patient in need thereof.
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- Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
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- Method and compositions for the treatment of pruritus
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A composition for treating pruritus, comprising a compound selected from the group consisting of opioid receptor antagonists, opioid receptor agonists/antagonists, and pharmaceutically acceptable salts thereof, and a compound useful in treating the cause of the pruritus. This invention also relates to a method of treating pruritus using such compositions, and a method for preparing these compositions.
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- A new method for the preparation of ifosfamide and cyclophosphamide
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The reaction of 2-chloro-3-(2-chloroethyl)-tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide 1 and 2-chloro-tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide 2 with 2-(trimethylsilyloxy)ethylamine 3 and bis-[2-(trimethylsiloxy)ethyl]amine 4, respectively, yielded the trimethylsilylated compounds 5 and 6, analogous to ifosfamide and cyclophosphamide. The reaction of 5 and 6 with 2-chloro-1,3,5-trimethyl-1,3,5-triaza-2-phosphorin-4,6-dione 7 led to the diphosphorus compounds 8 and 9 which could be transformed to ifosfamide 11 and cyclophosphamide 12 by treatment with sulfuryl chloride. This synthesis shows that the alkylating agents 2-chloroethylammonium chloride and bis-(2-chloroethyl)ammonium chloride can be avoided and the chlorine atom can be introduced in the final reaction step of the synthesis of 11 and 12.
- Neda,Sonnenburg,Schmutzler,Niemeyer,Kutscher,Engel,Kleemann
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p. 943 - 946
(2007/10/03)
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- Soluble phosphorylated glucan: methods and compositions for treatment of neoplastic diseases
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A new class of soluble phosphorylated glucans is described as well as the process for making the same. According to one embodiment, the soluble phosphorylated glucan is derived from the yeast Saccharomyces cerevisiae. The soluble phosphorylated glucans are useful for prophylactic and therapeutic applications against neoplastic, bacteria, viral, fungal and parasitic diseases. The soluble phosphorylated glucans are used either alone or in combination with a known antimicrobial agent for prophylactic and therapeutic antimicrobial applications. Additionally, they may be administered either alone or as a non-toxic adjuvant, in combination with chemotherapy. The soluble phosphorylated glucans are also useful for stimulating macrophage cells, either in vivo or in vitro, to produce a cytotoxic/cyctostatic factor effective against cancer cells.
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- Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
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A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
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- Aldophosphamides
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A compound having the structure STR1 wherein R is CH3 or C2 H5 1; R1 is NH2, NHCH3, NHC2 H5, NHC2 H4 Cl, N(CH3)2, N(C2 H5)2, N(C2 H4 Cl)2, OCH3, C2 H5, CH3, or C2 H5, and R2 is N(C2 H4 Cl)2 or NH C2 H4 Cl. These compounds may be used to eliminate occult leukemic clonogenic cells from bone marrow by contacting the bone marrow with a solution comprising levels of said compound sufficient to eliminate occult leukemic clonogenic cells. Analogously tumor cells in a host or organ of a host may be eliminated by treatment of the host or host's organ with a compound of this description. Compounds of this description are stable aldophosphamide analogs activatable by the action of an esterase and a subsequent E-2 elimination reaction to form acrolein and a phosphoramidic mustard of the formula: STR2 wherein R is NH2, NHCH3, NHC2 H5, NHC2 H4 Cl, N(CH3)2, N(C2 H5, N(C2 H4 Cl)2, OCH3, OC2 H5, CH3 or C2 H5.
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- Synthesis of 3-Hydroxycyclophosphamide and Studies Related to Its Possible Role in the Metabolism of Cyclophosphamide
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Hydrogenolysis of 3-(benzyloxy)cyclophosphamide (10) using Pd/C catalyst and ethyl acetate as solvent leads to the formation of 3-hydroxycyclophosphamide (3, ca. 20percent) and cyclophosphamide (1, ca. 10percent), accompanied by regioselective hydrogen-exchange reactions at the C-4 and C-5 positions in 3 and 1.A variety of oxidizing reagents and liver microsomal incubation failed to provide evidence (31P NMR) for conversion of 1 into 3, whereas identical incubation of 3 led to its reduction to 1.Compound 3 is stable at pH 6.5-8.2, 37 deg C, and exhibits anticancer activity comparable to 1 when tested against L1210 leukemia in mice.Data are discussed with regard to a previously reported suggestion that metabolism of 1 may involve oxidation to give 3 followed by rearrangement of 3 to 2.
- Brandt, Joan A.,Ludeman, Susan Marie,Zon, Gerald,Todhunter, John A.,Egan, William,Dickerson, Ruth
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p. 1404 - 1408
(2007/10/02)
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- Process for preparing cyclo-1,3,2-oxazaphosphoryl derivatives
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A novel process for preparing cyclo-1,3,2-oxazaphosphoryl derivatives represented by the formula (II), STR1 wherein R2 and R3 are respectively a lower alkyl group which may have halogen atom(s) or lower alkane-sulfonyloxy group(s) as substituted group(s) and n is an integer of 2 to 6, by acid cleaving the R1 --N bond of the compound represented by the formula (I), STR2 wherein R1 is an α-arylalkyl group, by using a strong acid, the compound represented by the formula (II) being effective as an anticancer agent.
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