公开(公告)号：US20060183931A1

公开(公告)日：2006-08-17

申请号：US10371155

申请日：2003-02-24

申请人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Dong Hwang ,  Jiyun Chen

发明人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Dong Hwang ,  Jiyun Chen

IPC分类号： C07F9/02 ,  C07F7/22 ,  C07C395/00 ,  C07C255/60 ,  C07C237/10

CPC分类号： C07C235/24

摘要： This invention provides androgen receptor targeting agents (ARTA). The agents define a new subclass of compounds, which are selective androgen receptor modulators (SARM). Several of the SARM compounds have been found to have an unexpected androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. Other SARM compounds have been found to have an unexpected antiandrogenic activity of a nonsteroidal ligand for the androgen receptor. 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; and/or g) decreasing the incidence of, halting or causing a regression of prostate cancer

摘要翻译： 本发明提供雄激素受体靶向剂（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）。 已经发现几种SARM化合物对雄激素受体具有非甾类化合物的意想不到的雄激素和合成代谢活性。 已经发现其他SARM化合物对雄激素受体具有非甾类配体的意想不到的抗雄激素活性。 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; 和/或g）降低前列腺癌的发生率，停止或导致消退

公开(公告)号：US20050209320A1

公开(公告)日：2005-09-22

申请号：US10963991

申请日：2004-10-14

申请人： Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Christina Barrett ,  Seoungsoo Hong

发明人： Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Christina Barrett ,  Seoungsoo Hong

IPC分类号： A61K20060101 ,  A61K31/165 ,  A61K31/277 ,  A61K31/325 ,  A61K39/395 ,  C07C235/24 ,  C07C255/60 ,  C07C271/24 ,  C07C309/87 ,  C07C317/40 ,  C07C323/60 ,  C07D207/448 ,  C07F9/09

CPC分类号： C07D207/448 ,  C07C215/76 ,  C07C235/16 ,  C07C235/24 ,  C07C255/60 ,  C07C271/24 ,  C07C309/87 ,  C07C317/46 ,  C07C323/60 ,  C07D233/74

摘要： The present invention relates to a novel class of anti-cancer compounds which selectively target androgen receptor (AR)-expressing cancer cells, such as prostate cancer cells and breast cancer cells. These agents comprise an androgen receptor (AR) binding moiety, which selectively targets the compounds to (AR)-expressing cancer cells, and a cytotoxic ablating moiety, such as a nitrogen mustard moiety. The inherent high density expression of the androgen receptor in certain cancers, such as prostate cancer and breast cancer, is thus used as a tool to selectively increase the intracellular concentration of cytotoxic compounds, such as alkylating agents, e.g. DNA alkylating agents, by selectively targeting the agents to the AR-expressing cancer cells. These agents, either alone or in a composition, are thus useful for treating, delaying the progression of, treating the recurrence of, suppressing, inhibiting or reducing the incidence of cancers characterized by the presence of AR-expressing cells, such as prostate cancer. Accordingly, the present invention provides a) methods of selectively killing an (AR)-expressing cancer cell; b) methods of inducing apoptosis in an (AR)-expressing cancer cell; c) methods of treating a cancer characterized by the presence of AR-expressing cells in a subject; d) methods of delaying the progression of a cancer characterized by the presence of AR-expressing cells in a subject; e) methods of treating the recurrence of a cancer characterized by the presence of AR-expressing cells in a subject; f) methods of suppressing, inhibiting or reducing the incidence of a cancer characterized by the presence of AR-expressing cells in a subject; and g) methods of treating metastasis of a cancer characterized by the presence of AR-expressing cells in a subject; by administering to the subject or by contacting the cancer cells with a compound comprising an androgen receptor ligand moiety and an alkylating moiety, such as the novel compounds described herein.

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：US20060009488A1

公开(公告)日：2006-01-12

申请号：US11013214

申请日：2004-12-16

申请人： Duane Miller ,  Mitchell Steiner ,  Karen Veverka

发明人： Duane Miller ,  Mitchell Steiner ,  Karen Veverka

IPC分类号： A61K31/4704 ,  C07D215/36

CPC分类号： C07F9/091 ,  A61K31/4704 ,  A61K47/548 ,  C07C235/24

摘要： The present invention provides prodrugs of selective androgen receptor modulators (SARMs), and their use in treating or reducing the incidence of osteoporosis, a variety of hormone-related conditions, conditions associated with Androgen Decline in Aging Male (ADAM); conditions associated with Androgen Decline in Female (ADIF), and muscular wasting conditions, obesity, dry eye conditions, and prostate cancer. The prodrugs are also useful in oral androgen replacement therapy and male contraception.

公开(公告)号：US20050033074A1

公开(公告)日：2005-02-10

申请号：US10861905

申请日：2004-06-07

申请人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Dong Hwang ,  Jiyun Chen

发明人： James Dalton ,  Duane Miller ,  Mitchell Steiner ,  Karen Veverka ,  Dong Hwang ,  Jiyun Chen

IPC分类号： C07C235/24 ,  C07F7/24 ,  C07C275/40 ,  C07C391/00

CPC分类号： C07C235/24

摘要： 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). Several of the SARM compounds have been found to have an unexpected androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. Other SARM compounds have been found to have an unexpected antiandrogenic activity of a nonsteroidal ligand for the androgen receptor. The SARM compounds, either alone or as a composition, are usefull 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; and/or g) decreasing the incidence of, halting or causing a regression of prostate cancer.

摘要翻译： 本发明提供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）。 已经发现几种SARM化合物对雄激素受体具有非甾类化合物的意想不到的雄激素和合成代谢活性。 已经发现其他SARM化合物对雄激素受体具有非甾类配体的意想不到的抗雄激素活性。 SARM化合物，单独或作为组合物，对于a）男性避孕是有用的; 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; 和/或g）降低前列腺癌的发生率，停止或导致消退。

公开(公告)号：US20050032750A1

公开(公告)日：2005-02-10

申请号：US10759538

申请日：2004-01-20

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

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

IPC分类号： A61K20060101 ,  A61K31/165 ,  A61K31/166 ,  A61K31/195 ,  A61K31/22 ,  A61K31/277 ,  A61K31/66

CPC分类号： A61K31/22 ,  A61K31/166

摘要： The present invention provides a method of treating, preventing, suppressing, inhibiting or reducing the incidence of an Androgen Deficiency in Female (ADIF)-associated condition in a female subject, by administering to the subject a selective androgen receptor modulator (SARM) compound and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, crystal, polymorph, prodrug, or any combination thereof. The present invention further provides a method of treating, preventing, suppressing, inhibiting or reducing the incidence of sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, fatigue, depression, anemia, muscle weakness, hair loss, obesity, polycystic ovarian disease, endometriosis, breast cancer, uterine cancer and ovarian cancer due to ADIF in a female subject, by administering to the subject a selective androgen receptor modulator (SARM) compound and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, crystal, polymorph, prodrug, or any combination thereof.

摘要翻译： 本发明提供了通过向受试者施用选择性雄激素受体调节剂（SARM）化合物和治疗雌激素受体调节剂（SARM）化合物的方法来治疗，预防，抑制，抑制或降低女性受试者中雄激素缺乏症（ADIF）相关病症的发生率 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，晶体，多晶型物，前药或其任何组合。 本发明还提供一种治疗，预防，抑制或降低性功能障碍，性欲降低，性腺机能减退，肌肉减少症，骨质减少症，骨质疏松症，认知和情绪改变，疲劳，抑郁，贫血，肌肉无力等的发生的方法， 通过向受试者施用选择性雄激素受体调节剂（SARM）化合物和/或其类似物，衍生物异构体，通过对雌性受试者的ADIF引起的脱发，肥胖，多囊卵巢疾病，子宫内膜异位症，乳腺癌，子宫癌和卵巢癌 ，代谢物，药学上可接受的盐，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：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：US20060258628A1

公开(公告)日：2006-11-16

申请号：US11184037

申请日：2004-07-20

申请人： Mitchell Steiner ,  Karen Veverka ,  Duane Miller

发明人： Mitchell Steiner ,  Karen Veverka ,  Duane Miller

IPC分类号： A61K31/555 ,  A61K31/44 ,  A61K31/4172 ,  A61K31/506 ,  A61K31/415 ,  A61K31/32 ,  A61K31/277 ,  A61K31/165 ,  A61K31/66

CPC分类号： A61K31/165 ,  A61K31/277 ,  A61K31/32 ,  A61K31/415 ,  A61K31/4172 ,  A61K31/44 ,  A61K31/506 ,  A61K31/555 ,  A61K31/66

摘要： This invention provides a composition comprising a 5-alpha reductase inhibitor and a class of androgen receptor targeting agents (ARTA), which are selective androgen receptor modulators (SARM). The compositions of this invention are useful for, inter-alia, 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 of polycystic ovarian disease; e) treatment and/or prevention of acute and/or chronic muscular wasting conditions; f) preventing and/or treating dry eye conditions; g) oral androgen replacement therapy; h) decreasing the incidence of, halting or causing a regression of prostate cancer; and/or i) inducing apoptosis in a cancer cell.

摘要翻译： 本发明提供包含5-α还原酶抑制剂和作为选择性雄激素受体调节剂（SARM）的一类雄激素受体靶向剂（ARTA）的组合物。 本发明的组合物尤其可用于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）治疗多囊卵巢疾病; e）治疗和/或预防急性和/或慢性肌肉消瘦病症; f）预防和/或治疗干眼症状; g）口服雄激素替代疗法; h）降低前列腺癌的发生率，停止或导致消退; 和/或i）诱导癌细胞中的细胞凋亡。