- Design, synthesis, anti-proliferative evaluation and docking studies of 1: H -1,2,3-triazole tethered ospemifene-isatin conjugates as selective estrogen receptor modulators
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A library of 1H-1,2,3-triazole-tethered ospemifene-isatin and ospemifene-spiroisatin conjugates have been synthesized and evaluated for their anti-proliferative activities against MCF-7 and MDA-MB-231 cell lines. The evaluation studies revealed that compound 11j was the most potent with an IC50 value of 1.56 μM against the MCF-7 cell line. Compounds 11k and 11l also displayed a similar trend, with several-fold lower effective concentrations in ER+ cells than in ER- cells. SAR studies revealed that conjugates having a bromo-substituent at the C-5 and C-7 positions of the isatin ring with ethyl/propyl as the spacer were observed to be active with the most potent compound being ~30 times more potent than Tamoxifen against the MCF-7 cell line. The evaluation results were further supported by docking studies and the stronger binding affinity of the synthesized conjugates was attributed to their greater structural bulk and greater occupation of the ERα active site.
- Kumar, Sumit,Gu, Liang,Palma, Gabriella,Kaur, Mandeep,Singh-Pillay, Ashona,Singh, Parvesh,Kumar, Vipan
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- Triarylethylene-indolin-2,3-dione molecular conjugates: Design, synthesis, docking studies and anti-proliferation evaluation
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A series of 1H-1,2,3-triazole-linked ospemifene-isatin and O-methylated ospemifene-isatin conjugates were synthesized and assayed for their anti-proliferative activities against estrogen-responsive as well as estrogen-non-responsive cells. The non-cytotoxic conjugate 14e, with an optimal combination of bromo substituents at the C-5/C-7 positions of isatin, proved to be a promising hit with an IC50 value of 31.62 μM against MCF-7 and 19.23 μM against MDA-MB-231. The observed anti-proliferative activities of active conjugates were further corroborated via docking studies carried out on estrogen receptor subtypes α and β.
- Kumar, Sumit,Palma, Gabriella,Perumal, Shanen,Kaur, Mandeep,Singh-Pillay, Ashona,Raj, Raghu,Singh, Parvesh,Kumar, Vipan
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- METHOD FOR PRODUCING TRIPHENYLBUTENE DERIVATIVE
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We provide a novel and useful process for preparing triphenyl-butene derivative. A process for the preparation of a compound represented by Formula (IV): wherein R1 is hydrogen or substituted or unsubstituted alkyl, characterized by reacting a compound represented by Formula (V): with a compound represented by Formula (VI): wherein R1 has the same meaning as defined above, in the presence of 1) a polyvalent metal chloride, 2) a reducing agent and 3) an alkali metal salt and/or a substituted or unsubstituted phenol.
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- Polymorphic forms of the formulations (by machine translation)
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The present invention provides formulations, the chemical name (Z)- 2 - [4 - (4 - chloro - 1, 2 - diphenyl - d - 1 - enyl) phenoxy] ethanol polymorphic forms, it has excellent stability, and can be a reproduction of the crystal structure. In addition, the present invention also provides formulations polymorph forms of preparation method. (by machine translation)
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Paragraph 0041; 0042; 0043
(2017/04/07)
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- PROCESS FOR THE PREPARATION OF OSPEMIFENE AND FISPEMIFENE
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Disclosed is a process for the synthesis of the active ingredients ospemifene and fispemifene which comprises reacting phenol 4 with an alkylating agent X- CH2CH2-Y of formula 7, wherein X is a leaving group and Y is the -(OCH2CH2)nOH group wherein n is zero or 1; or X and Y, taken together, represent an oxygen atom; to give ospemifene or fispemifene of formula 8.
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Page/Page column 6; 7
(2016/07/27)
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- PROCESS FOR PREPARATION OF OSPEMIFENE
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The present invention relates to a process for the preparation of ospemifene and pharmaceutically acceptable salts thereof which comprises the step of recycling the undesired E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol to generate an isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol.
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- METHODS FOR IMMUNOMODULATION OF CANCER AND INFECTIOUS DISEASE THERAPY
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The present invention provides methods for modulating the immune response of a subject to a therapeutic agent, the method comprising administering an effective amount of a triphenyl ethylene (TRIP) compound with an effective amount of the therapeutic agent. In particular embodiments, the TRIP compound enhances the immune response of the subject to the therapeutic agent. In some embodiments, the TRIP compound is administered in different dosing schedules to provide a biphasic immunomodulation effect.
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Paragraph 0197
(2016/07/27)
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- A PROCESS FOR THE PREPARATION OF OSPEMIFENE
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The present invention is related to the process for the preparation ospemifene or (Z)-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol (I) and to intermediate compounds used in the process.
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- A PROCESS FOR THE PREPARATION OF OSPEMIFENE
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The present invention is related to the process for the preparation ospemifene or (Z)-2-[4-(4-chloro-l,2-diphenyl-but-l-enyl)phenoxy]ethanol (I) and to intermediate compounds used in the process.
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Page/Page column 16
(2014/05/07)
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- NEW PROCESSES FOR PRODUCING BENZOPHENONE DERIVATIVES
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There is provided a process for the preparation of a compound of formula (I): wherein X, R1, R2a, R2b, R2c, R2d, R2e, R3a, R3b, R3c, R3d and R3e are as described in the description. Such compounds may, for example, be useful medicament (or intermediates for medicaments).
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Page/Page column 25-26
(2011/08/08)
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- METHOD FOR THE PREPARATION OF THERAPEUTICALLY VALUABLE TRIPHENYLBUTENE DERIVATIVES
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The present invention concerns a method for the preparation of therapeutically valuable triphenylbutene derivatives, especially ospemifene or fispemifene.
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Page/Page column 4
(2008/12/08)
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- Serum cholesterol lowering agent
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PCT No. PCT/FI97/00140 Sec. 371 Date Oct. 8, 1998 Sec. 102(e) Date Oct. 8, 1998 PCT Filed Mar. 4, 1997 PCT Pub. No. WO97/32574 PCT Pub. Date Sep. 12, 1997A method of lowering serum cholesterol levels comprising administering to a patient in need of such treatment an effective amount of Z-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol, as well as pharmaceutical compositions useful in the method, is disclosed.
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- Triphenylethylenes for the prevention and treatment of osteoporosis
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Compounds having formula (I) wherein R1 and R2 are independently H or OH, are useful in the treatment and prevention of osteoporosis. The compounds of formula (I) are devoid of significant antiestrogenic and estrogenic activity. STR1
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