公开(公告)号：US20110105445A1

公开(公告)日：2011-05-05

申请号：US12921932

申请日：2009-03-12

申请人： Vincent C.O. Njar ,  Angela Brodie

发明人： Vincent C.O. Njar ,  Angela Brodie

IPC分类号： A61K31/58 ,  A61P35/00

CPC分类号： A61K31/58 ,  A61K31/568

摘要： Provided are methods of inhibiting CYP17 in a mammal, such as a human, that include administering an effective amount of at least one CYP17 inhibitor, such as VN/124-1, VN/125-1, VN/85-1, VN/87-1 and/or VN/108-1 to the mammal. Also provided are methods of down regulating androgen receptor (AR) protein expression and methods of antagonizing AR in a mammal that include administering to the mammal an effective amount of at least one active ingredient selected from VN/124-1, VN/125-1, VN/85-1, VN/87-1 and VN/108-1. Also provided are methods of treating prostate cancer and methods of suppressing or preventing prostate tumor growth by administering such compounds to a mammal.

摘要翻译： 提供了抑制哺乳动物（例如人）中的CYP17的方法，其包括施用有效量的至少一种CYP17抑制剂，例如VN / 124-1，VN / 125-1，VN / 85-1，VN / 87-1和/或VN / 108-1。 还提供了下调哺乳动物的雄激素受体（AR）蛋白表达和拮抗AR的方法，其包括向哺乳动物施用有效量的至少一种选自VN / 124-1，VN / 125-1的活性成分 ，VN / 85-1，VN / 87-1和VN / 108-1。 还提供了通过向哺乳动物施用这种化合物来治疗前列腺癌的方法和抑制或预防前列腺肿瘤生长的方法。

公开(公告)号：US20120122908A1

公开(公告)日：2012-05-17

申请号：US11782938

申请日：2007-07-25

申请人： Vincent C.O. Njar ,  Angela M.H. Brodie ,  Ivo P. Nnane

发明人： Vincent C.O. Njar ,  Angela M.H. Brodie ,  Ivo P. Nnane

IPC分类号： A61K31/4164 ,  A61K31/4196 ,  A61K31/4418 ,  A61P35/00

CPC分类号： C07D249/08 ,  C07B2200/09 ,  C07C323/61 ,  C07C403/20 ,  C07C2601/16 ,  C07D213/55 ,  C07D231/12 ,  C07D233/54 ,  C07D233/56 ,  C07D303/38 ,  C07D331/02

摘要： C-4 substituted retinoic acid analogs, synthesis methods of C-4 substituted retinoic acid analogs and methods of using C-4 substituted retinoic acid analogs to treat various cancers and dermatological diseases and conditions. The C-4 substituted retinoic acid analogs include C-4 all-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-CRA) analogs. The C-4 substituted retinoic acid analogs inhibit all-trans retinoic acid (ATRA) 4-hydroxylase activity, thereby inhibiting the catabolism of ATRA. The C-4 substituted retinoic acid analogs also have ATRA-mimetic activity. The preferred substitutions at C-4 are an azole group, a sulfur, oxygen, or nitrogen containing group, a pyridyl group, an ethinyl group, a cyclopropyl-amine group, an ester group, or a cyano group, or forms, together with the C-4 carbon atom, an oxime, an oxirane or aziridine group.

摘要翻译： C-4取代的视黄酸类似物，C-4取代的视黄酸类似物的合成方法和使用C-4取代的视黄酸类似物治疗各种癌症和皮肤病学疾病和病症的方法。 C-4取代的视黄酸类似物包括C-4全反式视黄酸（ATRA）和13-顺式视黄酸（13-CRA）类似物。 C-4取代的视黄酸类似物抑制全反式视黄酸（ATRA）4-羟化酶活性，从而抑制ATRA的分解代谢。 C-4取代的视黄酸类似物也具有ATRA模拟活性。 C-4中优选的取代基是唑基，硫，氧或含氮基团，吡啶基，乙炔基，环丙基 - 胺基，酯基或氰基，或与 C-4碳原子，肟，环氧乙烷或氮丙啶基。

公开(公告)号：US20190169227A1

公开(公告)日：2019-06-06

申请号：US16310000

申请日：2017-06-22

申请人： Vincent C.O. Njar ,  Puranik Purushottamachar ,  Francis Murigi

发明人： Vincent C.O. Njar ,  Puranik Purushottamachar ,  Francis Murigi

IPC分类号： C07J43/00

摘要： Galeterone and its C-3 analogs are of substantial interest because of their multi-target anticancer activities, including AR and Mnk degrading activities. Provided are novel procedures for gram-scale, high-yield synthesis of C-3 analogs of galeterone, including 3β-(1H-imidazole-1-yl)-17-(1H-benzimidazole-1-yl)-androsta-5,16-diene (galeterone 3β-imidazole) and 3β-(pyridine-4-ylmethoxy)-17-(1H-benzimidazol-1-yl)androsta-5,16-diene (galeterone 3β-pyridine methoxylate).

公开(公告)号：US20110118219A1

公开(公告)日：2011-05-19

申请号：US12934135

申请日：2009-03-19

申请人： Vincent C.O. Njar ,  Angela M.H. Brodie ,  Lalji K. Gediya

发明人： Vincent C.O. Njar ,  Angela M.H. Brodie ,  Lalji K. Gediya

IPC分类号： A61K31/58 ,  C07D235/12 ,  C07D249/16 ,  C07D249/08 ,  C07D233/54 ,  C07D473/00 ,  A61P35/00

CPC分类号： A61K31/58 ,  A61K45/06 ,  C07J43/003 ,  A61K2300/00

摘要： Prodrugs of steroidal C-17 benzoazoles, pyrimidinoazoles(azabenzoazoles) and diazines. Methods of synthesis are also described, whereby a prodrug group is substituted for a functional group at A ring portion of the ABC ring structure of the steroid. Suitable prodrug groups include amino acid groups, succinate groups, phosphate groups, or sulfamate groups. The prodrugs of the disclosed compounds allow for improved oral bioavailability of the compounds that are inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds and the corresponding prodrugs are useful for the treatment of conditions such as human prostate cancer, breast cancer, and prostate hyperplasia.

摘要翻译： 类固醇C-17苯并唑类，嘧啶并唑类（氮杂苯并唑类）和二嗪类药物。 还描述了合成方法，由此前药基团被取代了类固醇的ABC环结构的A环部分的官能团。 合适的前药基团包括氨基酸基团，琥珀酸酯基团，磷酸酯基团或氨基磺酸酯基团。 所公开的化合物的前药允许改善作为人CYP17酶抑制剂的化合物的口服生物利用度以及野生型和突变体雄激素受体（AR）的有效拮抗剂。 化合物和相应的前药可用于治疗诸如人前列腺癌，乳腺癌和前列腺增生的病症。

公开(公告)号：US20160038476A1

公开(公告)日：2016-02-11

申请号：US14781437

申请日：2014-04-04

申请人： Vincent C.O. NJAR ,  Puranik PURUSHOTTAMACHAR ,  University of Maryland, Baltimore

发明人： Vincent C.O. Njar ,  Puranik Purushottamachar

IPC分类号： A61K31/4725 ,  A61K31/4164 ,  A61K31/4409 ,  A61K31/4184

CPC分类号： A61K31/4725 ,  A61K31/4164 ,  A61K31/4184 ,  A61K31/4409 ,  C07D235/08 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07J43/003

摘要： Nonsteroid and steroid compounds that cause down-regulation of the androgen receptor (AR), both full length and splice variant, induce apoptosis and inhibit proliferation of inhibiting proliferation and migration of androgen sensitive cancer cells. The steroid compounds and nonsteroid compounds may be agents for the prevention and/or treatment of cancer, including prostate cancer, castration resistant prostate cancer, bladder cancer, pancreatic cancer, hepatocellular carcinoma, benign prostatic hyperplasia (BPH), Kennedy's disease, androgenetic alopecia, breast cancer, androgen-insensitive syndrome, and spinal and bulbar muscular atrophy.

摘要翻译： 导致雄激素受体（AR）下调的非类固醇和类固醇化合物（全长和剪接变体）诱导凋亡并抑制雄激素敏感性癌细胞的增殖和迁移的增殖。 类固醇化合物和非类固醇化合物可以是用于预防和/或治疗癌症的药物，包括前列腺癌，抗阉割前列腺癌，膀胱癌，胰腺癌，肝细胞癌，良性前列腺增生症（BPH），肯尼迪氏病，雄激素性脱发， 乳腺癌，雄激素不敏感综合征，脊髓和延髓肌肉萎缩。