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：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：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：US20060276539A1

公开(公告)日：2006-12-07

申请号：US11324753

申请日：2006-01-04

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： A61K31/277

CPC分类号： A61K31/277 ,  C07K14/721

摘要： This invention provides methods for treatment and inhibition of a male subject having an Androgen Decline in Aging Male (ADAM)-associated condition, for example sexual dysfunction, decreased sexual libido, erectile dysfunction, hypogonadism, sarcopenia, osteopenia, osteoporosis, an alteration in cognition and mood, depression, anemia, hair loss, obesity, muscle loss, dry eye, memory loss, benign prostate hyperplasia and/or prostate cancer, 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, pro-drug, polymorph, crystal, or any combination thereof.

摘要翻译： 本发明提供了用于治疗和抑制雄性雄性雄激素降低（ADAM）相关病症的男性受试者的方法，例如性功能障碍，性欲性降低，勃起功能障碍，性腺机能减退，肌肉减少症，骨质减少症，骨质疏松症，认知改变 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，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，代谢物，药学上可接受的盐，药物产品，水合物，N-氧化物，前药，多晶型物，晶体或其任何组合。

公开(公告)号：US20060019989A1

公开(公告)日：2006-01-26

申请号：US10895401

申请日：2004-07-21

申请人： Mitchell Steiner ,  Karen Veverka ,  Duane Miller

发明人： Mitchell Steiner ,  Karen Veverka ,  Duane Miller

IPC分类号： A61K31/138 ,  A61K31/47

CPC分类号： A61K31/138 ,  A61K31/47 ,  A61K31/56 ,  A61K45/06 ,  A61K2300/00

摘要： This invention provides for combinations of 5 alpha reductase inhibitors and SERMs. These combinations are useful in: 1) preventing prostate carcinogenesis in a subject; 2) preventing the recurrence of, suppressing, inhibiting or reducing the incidence of prostate carcinogenesis in a subject; 3) treating a subject with prostate cancer; 4) suppressing, inhibiting or reducing the incidence of prostate cancer in a subject; 5) treating a subject with pre-malignant lesions of prostate cancer; 6) suppressing, inhibiting or reducing the incidence of pre-malignant lesions of prostate cancer in a subject; 7) reducing the incidence, inhibiting, suppressing, preventing and/or treating androgen-deprivation induced conditions in men suffering from prostate cancer, such as androgen-deprivation induced osteoporosis, bone fractures, loss of bone mineral density (BMD), hot flashes and/or gynecomastia; and 8) treating polycystic ovarian syndrome and reducing the incidence, inhibiting, suppressing, preventing and/or treating diabetes, cardiovascular disease, breast cancer and endometrial cancer in women suffering from polycystic ovarian syndrome.

摘要翻译： 本发明提供了5种α还原酶抑制剂和SERMs的组合。 这些组合可用于：1）预防受试者的前列腺癌发生; 2）预防受试者中前列腺癌发生的复发，抑制，抑制或降低; 3）用前列腺癌治疗受试者; 4）抑制或抑制受试者前列腺癌的发生率; 5）用前列腺癌的恶性前病变治疗受试者; 6）抑制，抑制或降低患者前列腺癌恶变前病变的发生率; 7）降低患有前列腺癌的男性的雄激素剥夺诱导的骨质疏松症，骨折，骨矿物质密度（BMD），潮热的闪烁和/或损伤的发生，抑制，抑制，预防和/或治疗雄激素剥夺诱导的病症 /或男子乳房发育症 和8）治疗多囊卵巢综合征，降低发生，抑制，抑制，预防和/或治疗患有多囊卵巢综合症的妇女的糖尿病，心血管疾病，乳腺癌和子宫内膜癌。

公开(公告)号：US20050080054A1

公开(公告)日：2005-04-14

申请号：US10683161

申请日：2003-10-14

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： C07K14/72 ,  A61K31/66 ,  A61K31/165 ,  A61K31/195 ,  A61K31/21 ,  A61K31/277 ,  A61K31/32

CPC分类号： C07K14/721

摘要： The present invention provides a method of treating, preventing, suppressing, inhibiting or reducing the incidence of an Androgen Decline in Aging Male (ADAM)-associated condition in a male 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, prodrug, polymorph, crystal, 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, erectile dysfunction, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, depression, anemia, hair loss, obesity, benign prostate hyperplasia or prostate cancer due to ADAM in a male 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, prodrug, polymorph, crystal, 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，治疗，预防，抑制，抑制或降低男性受试者的老年男性（ADAM）相关状态的雄激素下降的发生率的方法 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，前药，多晶型物，晶体或其任何组合。 本发明还提供了治疗，预防，抑制或降低性功能障碍，性欲降低，勃起功能障碍，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，抑郁症，贫血，脱发 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，代谢产物，药学上可接受的盐，药物产品，由此引起的ADAM在男性受试者中的肥胖，良性前列腺增生或前列腺癌。 水合物，N-氧化物，前药，多晶型物，晶体或其任何组合。

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。

公开(公告)号：US20060111441A1

公开(公告)日：2006-05-25

申请号：US11220414

申请日：2005-09-07

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： A61K31/277

CPC分类号： A61K31/277

摘要： This invention provides: 1) a method of treating a subject suffering from a muscle wasting disorder; 2) a method of preventing a muscle wasting disorder in a subject; 3) a method of treating, preventing, suppressing, inhibiting or reducing muscle loss in a subject suffering from a muscle wasting disorder; 4) a method of treating, preventing, inhibiting, reducing or suppressing muscle wasting in a subject suffering from a muscle wasting disorder; and/or 5) a method of treating, preventing, inhibiting, reducing or suppressing muscle protein catabolism in a subject suffering from a muscle wasting disorder, by administering to the subject a selective androgen receptor modulator (SARM) and/or an analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, prodrug, polymorph, impurity or crystal of said SARM compound, or any combination thereof.

摘要翻译： 本发明提供：1）治疗患有肌肉消瘦障碍的受试者的方法; 2）预防受试者的肌肉消瘦障碍的方法; 3）治疗，预防，抑制，抑制或减轻患有肌肉消瘦障碍的受试者的肌肉损失的方法; 4）一种治疗，预防，抑制，减少或抑制患有肌肉消瘦障碍的受试者的肌肉消瘦的方法; 和/或5）通过向受试者施用选择性雄激素受体调节剂（SARM）和/或类似物衍生物，治疗，预防，抑制，减少或抑制患有肌肉消瘦疾病的受试者的肌肉蛋白分解代谢的方法 ，所述SARM化合物的异构体，代谢物，药学上可接受的盐，药物产品，水合物，N-氧化物，前药，多晶型物，杂质或晶体，或其任何组合。