公开(公告)号：US20060035966A1

公开(公告)日：2006-02-16

申请号：US10995567

申请日：2004-11-24

申请人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Leonid Kirkovsky ,  Dong Hwang ,  Arnab Mukherjee

发明人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Leonid Kirkovsky ,  Dong Hwang ,  Arnab Mukherjee

IPC分类号： C07C331/28

CPC分类号： C07C323/60 ,  A61K31/16 ,  A61K31/26 ,  A61K31/275 ,  C07C261/02 ,  C07C265/12 ,  C07C331/10 ,  C07C331/28

摘要： In one embodiment, this invention provides a class of androgen receptor targeting agents (ARTA). The agents define a new subclass of compounds, which are selective androgen receptor modulators (SARM). The SARM compounds have unexpected antiandrogenic activity of a nonsteroidal ligand for the androgen receptor. In one embodiment, the SARM compounds bind irreversibly to the androgen receptor In another embodiment, the SARM compounds are androgen receptor antagonists, which bind irreversibly to the androgen receptor. In another embodiment, the SARM compounds are alkylating agents. The SARM compounds, either alone or as a composition, are useful for a) male contraception; b) treatment of a variety of hormone-related conditions, for example conditions associated with Androgen Decline in Aging Male (ADAM), such as fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, osteoporosis, benign prostate hyperplasia, alterations in mood and cognition and prostate cancer; c) treatment of conditions associated with Androgen Decline in Female (ADIF), such as sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, depression, anemia, hair loss, obesity, endometriosis, breast cancer, uterine cancer and ovarian cancer; d) treatment and/or prevention of acute and/or chronic muscular wasting conditions; e) preventing and/or treating dry eye conditions; f) oral androgen replacement therapy; g) decreasing the incidence of, halting or causing a regression of prostate cancer; and/or h) inducing apoptosis in a cancer cell.

摘要翻译： 在一个实施方案中，本发明提供了一类雄激素受体靶向剂（ARTA）。 这些药剂定义了一种新的化合物亚类，它们是选择性雄激素受体调节剂（SARM）。 SARM化合物对雄激素受体的非甾体配体具有意想不到的抗雄激素活性。 在一个实施方案中，SARM化合物不可逆地与雄激素受体结合。在另一个实施方案中，SARM化合物是雄激素受体拮抗剂，其不可逆地结合雄激素受体。 在另一个实施方案中，SARM化合物是烷化剂。 SARM化合物，单独或作为组合物，可用于a）男性避孕; b）治疗各种激素相关病症，例如与老年雄性雄激素降低有关的病症（ADAM），如疲劳，抑郁，性欲降低，性功能障碍，勃起功能障碍，性腺机能减退，骨质疏松症，脱发，贫血， 肥胖，肌营养不良，骨质减少，骨质疏松症，良性前列腺增生，情绪和认知和前列腺癌的改变; c）治疗与男性雄激素降低相关的病症（ADIF），如性功能障碍，性欲降低，性腺机能减退，肌营养不良，骨质减少，骨质疏松症，认知和情绪改变，抑郁症，贫血，脱发，肥胖，子宫内膜异位症，乳腺癌 癌症，子宫癌和卵巢癌; d）治疗和/或预防急性和/或慢性肌肉消瘦病症; e）预防和/或治疗干眼症状; f）口服雄激素替代疗法; g）降低前列腺癌的发生率，停止或导致消退; 和/或h）诱导癌细胞中的细胞凋亡。

公开(公告)号：US20050080055A1

公开(公告)日：2005-04-14

申请号：US10760152

申请日：2004-01-20

申请人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka

发明人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka

IPC分类号： A61K20060101 ,  A61K31/165 ,  A61K31/21 ,  A61K31/26 ,  A61K31/277 ,  A61K31/32 ,  A61K31/66 ,  A61P35/00

CPC分类号： A61K31/66 ,  A61K31/21 ,  A61K31/26

摘要： This invention relates to the prevention and treatment of breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of a) treating a subject suffering from breast cancer; b) preventing, suppressing, inhibiting or reducing the incidence of breast cancer in a subject; c) delaying the progression of breast cancer in a subject suffering from breast cancer; d) preventing the recurrence of breast cancer in a subject; e) treating the recurrence of breast cancer in a subject suffering from breast cancer; and/or f) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer, by administering to the subject a therapeutically effective amount of an Androgen Receptor Antagonist and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, crystal, polymorph, prodrug or any combination thereof, as described herein.

摘要翻译： 本发明涉及预防和治疗受试者，例如女性受试者的乳腺癌。 因此，本发明提供了a）治疗患有乳腺癌的受试者的方法; b）预防，抑制，抑制或降低患者乳腺癌的发生率; c）延缓乳腺癌患者乳腺癌的进展; d）预防受试者乳腺癌的复发; e）治疗乳腺癌患者乳腺癌的复发; 和/或f）通过向受试者施用治疗有效量的雄激素受体拮抗剂和/或其类似物，衍生物，异构体，代谢物，药学上可接受的盐，治疗，预防，抑制或抑制患有乳腺癌的受试者的转移 ，药物产品，水合物，N-氧化物，晶体，多晶型物，前药或其任何组合。

公开(公告)号：US20050038110A1

公开(公告)日：2005-02-17

申请号：US10863524

申请日：2004-06-09

申请人： Mitchell Steiner ,  James Dalton ,  Duane Miller ,  Karen Veverka

发明人： Mitchell Steiner ,  James Dalton ,  Duane Miller ,  Karen Veverka

IPC分类号： A61K31/277 ,  A61K31/32 ,  C07F7/24

CPC分类号： C07C255/60 ,  C07C235/24 ,  C07C255/54

摘要： This invention provides a class of androgen receptor targeting agents. The agents define a new subclass of compounds, which are selective androgen receptor modulators (SARM).

摘要翻译： 本发明提供一类雄激素受体靶向剂。 这些药剂定义了一种新的化合物亚类，它们是选择性雄激素受体调节剂（SARM）。

公开(公告)号：US20050080143A1

公开(公告)日：2005-04-14

申请号：US10944465

申请日：2004-09-20

申请人： Mitchell Steiner ,  Karen Veverka ,  Sharan Raghow

发明人： Mitchell Steiner ,  Karen Veverka ,  Sharan Raghow

IPC分类号： A61K31/138

CPC分类号： A61K31/135 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0021 ,  A61K9/0024 ,  A61K9/0053 ,  A61K31/138

摘要： The present invention provides methods for reducing the incidence of, inhibiting, suppressing, reducing the incidence of, and treating androgen-deprivation induced osteoporosis, bone fractures and/or loss of bone mineral density (BMD) in men having prostate cancer, comprising administering to a male human subject having prostate cancer a toremifene and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof. The present invention also provides methods of treating, preventing, suppressing, inhibiting, or reducing the incidence of hot flashes, gynecomastia, and/or hair loss in male humans having prostate cancer, comprising same.

摘要翻译： 本发明提供了减少在具有前列腺癌的男性中发生，抑制，抑制，降低发生和治疗雄激素剥夺诱导的骨质疏松症，骨折和/或骨矿物质密度（BMD）丧失的方法，包括给予 具有前列腺癌托泊米芬和/或其类似物，衍生物，异构体，代谢物，药学上可接受的盐，药物产品，水合物，N-氧化物或其任何组合的男性受试者。 本发明还提供了治疗，预防，抑制或抑制具有前列腺癌的男性人群中的潮热，男子女性发育和/或脱发的发生的方法。

公开(公告)号：US20070197664A1

公开(公告)日：2007-08-23

申请号：US11656566

申请日：2007-01-23

申请人： Mitchell Steiner ,  Sharan Raghow ,  Karen Veverka

发明人： Mitchell Steiner ,  Sharan Raghow ,  Karen Veverka

IPC分类号： A61K31/135

CPC分类号： A61K31/138 ,  A61K31/135

摘要： This invention provides a method of treatment, prevention, suppression, inhibition, or reduction of risk of developing androgen-deprivation induced skeletal-related events (SRE), such as pathologic fractures, surgery to bone, radiation to bone, spinal cord compression, change in antineoplastic therapy, including changes in hormonal therapy, new bone metastases, bone loss, or a combination thereof in men suffering from prostate cancer, comprising administering to a male subject suffering from prostate cancer a selective estrogen receptor modulator (SERM) and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.

摘要翻译： 本发明提供了治疗，预防，抑制，抑制或降低发展中的雄激素剥夺诱导的骨骼相关事件（SRE）的风险的方法，例如病理性骨折，骨骼手术，对骨骼的放射，脊髓压迫，变化 包括对患有前列腺癌的男性的激素治疗，新骨转移，骨丢失或其组合的改变，包括对患有前列腺癌的男性受试者施用选择性雌激素受体调节剂（SERM）和/或其 类似物，衍生物，异构体，代谢物，药学上可接受的盐，药物产品，水合物，N-氧化物或其任何组合。

公开(公告)号：US20060287282A1

公开(公告)日：2006-12-21

申请号：US11003938

申请日：2004-12-06

申请人： Mitchell Steiner ,  Karen Veverka

发明人： Mitchell Steiner ,  Karen Veverka

IPC分类号： A61K31/675 ,  A61K31/555 ,  A61K31/277 ,  A61K31/32 ,  A61K31/165

CPC分类号： A61K31/165 ,  A61K31/277 ,  A61K31/32 ,  A61K31/555 ,  A61K31/675

摘要： The present invention relates to compositions comprising a selective androgen receptor modulators (SARM) and a gonadotropin releasing hormone (GnRH) agonist or a GnRH antagonist, and their use, inter-alia for treating hormone-associated conditions in males and females, which arise as a result of androgen decline, suppression or abrogation, or in treating, suppressing, inhibiting or preventing prostate cancer.

摘要翻译： 本发明涉及包含选择性雄激素受体调节剂（SARM）和促性腺激素释放激素（GnRH）激动剂或GnRH拮抗剂的组合物，以及它们用于治疗男性和女性的激素相关病症，其出现为 雄激素降低，抑制或消除的结果，或治疗，抑制，抑制或预防前列腺癌的结果。

公开(公告)号：US20060269611A1

公开(公告)日：2006-11-30

申请号：US11329393

申请日：2006-01-11

申请人： Mitchell Steiner ,  Sharan Raghow ,  Karen Veverka

发明人： Mitchell Steiner ,  Sharan Raghow ,  Karen Veverka

IPC分类号： A61K9/14 ,  A61K31/138

CPC分类号： A61K31/138

摘要： This invention provides a method of treating androgen-deprivation induced osteoporosis, bone fractures or loss of bone mineral density (BMD) in a male human subject suffering from prostate cancer by administering a pharmaceutical composition comprising Toremifene and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof, to the subject.

摘要翻译： 本发明提供了一种通过给药含有托瑞米芬和/或其类似物，衍生物，异构体的药物组合物来治疗患有前列腺癌的男性人体中的雄激素剥夺诱导的骨质疏松症，骨折或骨矿物质密度（BMD）丧失的方法， 代谢产物，药学上可接受的盐，药物产品，水合物，N-氧化物或其任何组合。

公开(公告)号：US20060270641A1

公开(公告)日：2006-11-30

申请号：US11140255

申请日：2005-05-31

申请人： Mitchell Steiner ,  Sharan Raghow

发明人： Mitchell Steiner ,  Sharan Raghow

IPC分类号： A61K31/56 ,  A61K31/453 ,  A61K31/138

CPC分类号： A61K31/138 ,  A61K31/453 ,  A61K31/56

摘要： This invention relates to the chemoprevention of prostate cancer and, more particularly, to a method of suppressing or inhibiting latent prostate cancer comprising administering to a mammalian subject a chemopreventive agent, for example raloxifene, or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, ester, or N-oxide, or mixtures thereof. The chemopreventive agent prevents, prevents recurrence of, suppresses or inhibits prostate carcinogenesis and treats prostate cancer.

摘要翻译： 本发明涉及前列腺癌的化学预防，更具体地，涉及一种抑制或抑制潜伏性前列腺癌的方法，包括向哺乳动物受试者施用化学预防药物，例如雷洛昔芬或其类似物，衍生物，异构体，代谢物，药学上可接受的 盐，酯或N-氧化物，或其混合物。 化学预防剂防止，预防复发，抑制或抑制前列腺癌发生和治疗前列腺癌。

公开(公告)号：US20060287400A1

公开(公告)日：2006-12-21

申请号：US11132425

申请日：2005-05-19

申请人： Mitchell Steiner ,  Sharan Raghow

发明人： Mitchell Steiner ,  Sharan Raghow

IPC分类号： A61K31/138 ,  A61K31/05 ,  A61K31/02

CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/015 ,  A61K31/02 ,  A61K31/05 ,  A61K31/138 ,  A61K31/4535 ,  A61K31/565

摘要： This invention relates to the treatment and prevention of prostate cancer More particularly, the present invention provides 1) methods of preventing prostate carcinogenesis in a subject; 2) methods of preventing the recurrence of, suppressing, inhibiting or reducing the incidence of prostate carcinogenesis in a subject, 3) methods of treating a subject with prostate cancer; 4) methods of suppressing, inhibiting or reducing the incidence of prostate cancer in a subject; 5) methods of treating a subject with pre-malignant lesions of prostate cancer, and 6) methods of suppressing, inhibiting or reducing the incidence of pre-malignant lesions of prostate cancer in a subject by administering to the subject a compound of formula (I) or an analog or metabolite thereof, its N-oxide, ester, pharmaceutically acceptable salt, hydrate, or any combination thereof as described herein. The present invention provides a safe and effective method for suppressing or inhibiting prostate cancer, e.g. latent prostate cancer, and is particularly useful for treating subjects having an elevated risk of developing prostate cancer, for example, those having benign prostatic hyperplasia, prostate intraepithelial neoplasia (PIN), or an abnormally high level of circulating prostate specific antibody (PSA), or having a family history of prostate cancer.

摘要翻译： 本发明涉及治疗和预防前列腺癌。更具体地，本发明提供1）预防受试者中前列腺癌发生的方法; 2）预防受试者的前列腺癌发生发生的复发，抑制，抑制或降低的方法，3）用前列腺癌治疗受试者的方法; 4）抑制或抑制受试者前列腺癌发病率的方法; 5）治疗患有前列腺癌的恶性前病变的受试者的方法，以及6）通过向受试者施用式（I）的化合物来抑制，抑制或降低患者前列腺癌的恶性前病变发病率的方法 ）或其类似物或代谢物，其N-氧化物，酯，药学上可接受的盐，水合物或其任何组合。 本发明提供了一种安全有效的抑制或抑制前列腺癌的方法，例如， 潜伏性前列腺癌，并且特别可用于治疗具有升高的前列腺癌风险的受试者，例如具有良性前列腺增生，前列腺上皮内瘤变（PIN）或异常高水平的循环前列腺特异性抗体（PSA）的受试者， 或具有前列腺癌的家族史。

公开(公告)号：US20050171073A1

公开(公告)日：2005-08-04

申请号：US11038468

申请日：2005-01-21

申请人： Mitchell Steiner ,  Sharan Raghow

发明人： Mitchell Steiner ,  Sharan Raghow

IPC分类号： A61K31/00 ,  A61K31/015 ,  A61K31/138 ,  A61K31/4535 ,  A61K31/565 ,  A61K45/06 ,  A61K31/58 ,  A61K31/57

CPC分类号： A61K45/06 ,  A61K31/00 ,  A61K31/015 ,  A61K31/02 ,  A61K31/05 ,  A61K31/138 ,  A61K31/4535 ,  A61K31/565

摘要： This invention relates to compositions and methods of use thereof in the prevention of prostate carcinogenesis in a subject; prevention of the recurrence of, suppression, inhibition or reduction of the incidence of prostate carcinogenesis in a subject; treatment of a subject with prostate cancer; suppression, inhibition or reduction of the incidence of prostate cancer in a subject; treatment of a subject with pre-malignant lesions of prostate cancer; and/or suppression, inhibition or reduction of the incidence of pre-malignant lesions of prostate cancer in a subject.

摘要翻译： 本发明涉及其用于预防受试者中前列腺癌发生的组合物及其方法; 预防受试者中前列腺癌发生发生的复发，抑制，抑制或减少; 治疗患有前列腺癌的受试者; 抑制，抑制或减少受试者中前列腺癌的发生率; 治疗患有前列腺癌恶变前病变的受试者; 和/或抑制，抑制或降低受试者中前列腺癌的恶性前病变的发生率。