公开(公告)号：US20160207930A1

公开(公告)日：2016-07-21

申请号：US14913647

申请日：2014-08-15

Applicant: LEO PHARMA A/S

Inventor： Haakan BLADH ,  Jakob FELDING ,  Ding ZHOU ,  Zhen-wei CAI ,  Morten Dahl SØRENSEN

IPC: C07D487/04 ,  A61K9/00 ,  A61K31/4985

CPC classification number: C07D487/04 ,  A61K9/0014 ,  A61K31/4985

Abstract: The invention relates novel NK1 receptor antagonists represented in formula A, wherein R1 and R2 independently are selected from the group consisting of (C1-4)alkyl, (C1-4)haloalkyl, (C1-4)alkoxy, CD3 or halogen; R3 is selected from the group consisting of hydrogen, (C1-4)alkyl, (C1-4)haloalkyl and (C1-4)hydroxyalkyl; R4 is selected from the group consisting of phenyl, 5-membered heteroaryl and 6-membered heteroaryl; R5 and R6 are independently selected from the group consisting of hydrogen, (C1-4)alkyl, (C1-4) hydroxyalkyl and (C1-4)haloalkyl and X and Y are independently selected from the group consisting of CH and N. The invention furthermore relates to intermediates for the preparation of said compounds, to their use in therapy, and to pharmaceutical compositions comprising said compounds.

Abstract translation: 本发明涉及式A中所示的新型NK1受体拮抗剂，其中R1和R2独立地选自（C1-4）烷基，（C1-4）卤代烷基，（C1-4）烷氧基，CD3或卤素; R3选自氢，（C1-4）烷基，（C1-4）卤代烷基和（C1-4）羟基烷基; R4选自苯基，5元杂芳基和6元杂芳基; R 5和R 6独立地选自氢，（C 1-4）烷基，（C 1-4）羟基烷基和（C 1-4）卤代烷基，X和Y独立地选自CH和N。 本发明还涉及制备所述化合物的中间体，其在治疗中的用途以及包含所述化合物的药物组合物。

公开(公告)号：US09346809B2

公开(公告)日：2016-05-24

申请号：US13382665

申请日：2010-07-08

Applicant: Simon Feldbæk Nielsen ,  Daniel Rodriguez Greve ,  Carsten Ryttersgaard ,  Gunnar Grue-Sørensen ,  Erik Rytter Ottosen ,  Tina Dahlerup Poulsen ,  Søren Christian Schou ,  Anthony Murray

Inventor： Simon Feldbæk Nielsen ,  Daniel Rodriguez Greve ,  Carsten Ryttersgaard ,  Gunnar Grue-Sørensen ,  Erik Rytter Ottosen ,  Tina Dahlerup Poulsen ,  Søren Christian Schou ,  Anthony Murray

IPC: C07D487/04 ,  C07D519/00 ,  A61K31/519 ,  C07D471/04 ,  A61P37/00 ,  A61P19/02 ,  A61P25/28 ,  A61P35/00 ,  A61P11/06 ,  A61P3/10 ,  A61P17/06 ,  A61P17/14 ,  A61P17/10 ,  A61P17/00 ,  A61P17/08 ,  A61P17/04 ,  A61P19/06 ,  A61P11/00

CPC classification number: C07D487/04 ,  C07D471/04 ,  C07D519/00

Abstract: The invention relates to compounds of general formula (I) wherein A, R1, R2, R3, R4, R5, R9, m and n are defined as defined herein, and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use—alone or in combination with one or more other pharmaceutically active compounds—in therapy, as JAK kinase and protein tyrosine kinase inhibitors for preventing, treating or ameliorating diseases and complications thereof, including, for example, psoriasis, atopic dermatitis, rosacea, lupus, multiple sclerosis, rheumatoid arthritis, Type I diabetes, asthma, cancer, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukaemia, eye diseases such as diabetic retinopathy and macular degeneration as well as other autoimmune diseases and indications where immunosuppression would be desirable for example in organ transplantation.

Abstract translation: 本发明涉及通式（I）的化合物，其中A，R 1，R 2，R 3，R 4，R 5，R 9，m和n如本文所定义，及其药学上可接受的盐，水合物或溶剂化物， 或与一种或多种其它药物活性化合物组合，作为用于预防，治疗或改善疾病及其并发症的JAK激酶和蛋白酪氨酸激酶抑制剂，包括例如牛皮癣，特应性皮炎，酒渣鼻，狼疮，多发性硬化 ，类风湿性关节炎，I型糖尿病，哮喘，癌症，自身免疫性甲状腺疾病，溃疡性结肠炎，克罗恩病，阿尔茨海默病，白血病，眼睛疾病如糖尿病性视网膜病变和黄斑变性以及其他自身免疫性疾病和适应症，其中需要免疫抑制 器官移植的例子。

公开(公告)号：US09233964B2

公开(公告)日：2016-01-12

申请号：US13977408

申请日：2012-01-06

Applicant: Søren Christian Schou ,  Daniel Rodriguez Greve ,  Simon Feldbæk Nielsen ,  Jens Bjørn Jensen ,  Kevin Neil Dack

Inventor： Søren Christian Schou ,  Daniel Rodriguez Greve ,  Simon Feldbæk Nielsen ,  Jens Bjørn Jensen ,  Kevin Neil Dack

IPC: A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  C07D487/04 ,  A61K31/5377 ,  A61K45/06

CPC classification number: C07D487/04 ,  A61K31/519 ,  A61K31/5377 ,  A61K45/06

Abstract: The invention relates to compounds of general Formula (I), Wherein R1, R2, R3, R4, R5, m, n are defined herein, and pharmaceutically acceptable salts, prodrugs, hydrates, or solvates thereof, for use—alone or in combination with one or more other pharmaceutically active compounds—in therapy, as JAK kinase and protein tyrosine kinase inhibitors for preventing, treating or ameliorating diseases and complications thereof, including, for example, psoriasis, atopic dermatitis, rosacea, lupus, multiple sclerosis, rheumatoid arthritis, Type I diabetes, asthma, cancer, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukaemia, eye diseases such as diabetic retinopathy and macular degeneration as well as other autoimmune diseases and indications where immunosuppression would be desirable for example in organ transplantation.

Abstract translation: 本发明涉及通式（I）的化合物，其中R1，R2，R3，R4，R5，m，n如本文所定义，及其药学上可接受的盐，前体药物，水合物或溶剂化物，单独使用或组合使用 与治疗中的一种或多种其它药物活性化合物一起作为用于预防，治疗或改善疾病及其并发症的JAK激酶和蛋白酪氨酸激酶抑制剂，包括例如牛皮癣，特应性皮炎，酒渣鼻，狼疮，多发性硬化，类风湿性关节炎 ，I型糖尿病，哮喘，癌症，自身免疫性甲状腺疾病，溃疡性结肠炎，克罗恩病，阿尔茨海默氏病，白血病，眼睛疾病如糖尿病性视网膜病变和黄斑变性以及其他自身免疫性疾病和免疫抑制在器官中是理想的适应症 移植。

公开(公告)号：US20150196646A1

公开(公告)日：2015-07-16

申请号：US14410489

申请日：2013-07-05

Applicant: LEO PHARMA A/S

Inventor： Karsten Petersson ,  Kit Frederiksen ,  Diana Omkvist ,  Jörgen Jansson

IPC: A61K47/32 ,  A61K47/22 ,  A61K47/10 ,  A61K31/573 ,  A61K47/14

CPC classification number: A61K31/573 ,  A61K9/0014 ,  A61K9/124 ,  A61K9/7015 ,  A61K47/06 ,  A61K47/08 ,  A61K47/10 ,  A61K47/14 ,  A61K47/22 ,  A61K47/26 ,  A61K47/32 ,  A61K47/38 ,  A61K47/44 ,  B65D83/752

Abstract: A film-forming pharmaceutical composition for dermal application comprises at least one therapeutically active ingredient dissolved in a volatile solvent, the composition further comprising a film-forming polymer, a plasticizer and an oily release-enhancing agent. The composition is capable of forming, after application on skin and evaporation of the solvent, a continuous phase comprising the film-forming polymer and the plasticizer and a dispersed phase comprising droplets of the oily release-enhancing agent.

Abstract translation: 用于真皮施用的成膜药物组合物包含溶解在挥发性溶剂中的至少一种治疗活性成分，所述组合物还包含成膜聚合物，增塑剂和油性释放增强剂。 组合物能够在皮肤上施用和蒸发溶剂后形成包含成膜聚合物和增塑剂的连续相和包含油性释放增强剂的液滴的分散相。

公开(公告)号：US09056814B2

公开(公告)日：2015-06-16

申请号：US13806690

申请日：2011-06-24

Applicant: Soren Ebdrup ,  Kim Troensegaard Nielsen ,  Tanja Maria Greve

Inventor： Soren Ebdrup ,  Kim Troensegaard Nielsen ,  Tanja Maria Greve

IPC: C07C43/20 ,  A61K31/075 ,  C07C217/74 ,  C07C213/10 ,  A61K31/196 ,  A61K31/592 ,  A61K31/593

CPC classification number: C07C217/74 ,  A61K31/196 ,  A61K31/592 ,  A61K31/593 ,  C07C213/10 ,  C07C2601/08

Abstract: The present invention relates to the crystalline, polymorphic Form C of the calcimimetic compound {4-[(1R,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid, to methods of preparation thereof, to methods of characterization thereof by single crystal X-Ray crystallography (XRC), X-Ray Powder diffractometry, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Solid State NMR spectroscopy and Differential Scanning Calorimetry (DSC), and to its use. The invention also relates to the preparation of Form C by crystallization from a saturated solution of {4-[(1R,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid in the presence of crystallization seeds of Form C, or alternatively by conversion of an amorphous starting material into the different crystalline polymorphic Form X by crystallization of {4-[(1R,3S)-3-((R)-1-Naphthalen-1-yl-ethylamino)-cyclopentyl]-phenoxy}-acetic acid, followed by a solid solution transformation thereof into the desired polymorphic Form C.

Abstract translation: 本发明涉及拟钙化合物{4 - [（1R，3S）-3 - （（R）-1-萘基-1-乙基氨基） - 环戊基] - 苯氧基} - 乙酸的结晶多晶型C 酸，其制备方法，通过单晶X射线晶体学（XRC），X射线粉末衍射，衰减全反射傅立叶变换红外（ATR-FTIR）光谱，固态NMR光谱和差示扫描的表征方法 量热法（DSC）及其用途。 本发明还涉及通过从饱和的{4 - [（1R，3S）-3 - （（R）-1-萘基-1-基 - 乙基氨基） - 环戊基] - 苯氧基} - 乙酸在形式C的结晶晶种存在下，或者通过{4 - [（1R，3S）-3 - （（R）-1）的结晶将无定形原料转化成不同结晶多晶型X 萘-1-基 - 乙基氨基） - 环戊基] - 苯氧基} - 乙酸，然后将其固溶转化为所需的多晶型C.

公开(公告)号：USD725470S1

公开(公告)日：2015-03-31

申请号：US29434939

申请日：2012-10-18

Applicant: LEO Pharma A/S

Designer： Alun Wilcox ,  Peter Sprada ,  Graeme Howard Davies ,  Nicholas Henry Reddall ,  Joshua Thomas Richards

公开(公告)号：US20140323993A1

公开(公告)日：2014-10-30

申请号：US14007349

申请日：2012-03-08

Applicant: Alun Wilcox ,  Peter Sprada ,  Alexandra Louisa Faraday Crook ,  Steven William McLellan ,  Graham Keith Lacy ,  Julian Francis Ralph Swan

Inventor： Alun Wilcox ,  Peter Sprada ,  Alexandra Louisa Faraday Crook ,  Steven William McLellan ,  Graham Keith Lacy ,  Julian Francis Ralph Swan

IPC: A61M35/00

CPC classification number: A61M35/003 ,  A45D2200/055 ,  A61H7/003 ,  A61H2201/105 ,  A61H2201/5043 ,  B65D83/0011 ,  B65D2203/00

Abstract: An applicator for topically applying a semi-solid medicament comprises an applicator head having an applicator face for spreading medicament across the skin; a sealable aperture on the applicator face; and a drive mechanism for forcing medicament out through the aperture. The applicator head includes a cartridge port at the rear of the applicator face for receiving a dispensing end of a cartridge charged with medicament. The drive mechanism comprises a dial knob rotatable around a longitudinal axis of the applicator for advancing a piston along a drive member towards the applicator head to force medicament from the cartridge and thereby dispense a predetermined dose of medicament onto the applicator face.

Abstract translation: 用于局部施用半固体药物的施用器包括具有施用器面的施用器头，用于将药剂穿过皮肤; 施加器表面上的可密封的孔; 以及驱动机构，用于迫使药物通过孔径流出。 施用器头包括在施用器面的后部的药筒端口，用于接收带有药物的药筒的分配端。 驱动机构包括可围绕施加器的纵向轴线旋转的拨盘旋钮，用于使活塞沿着驱动构件朝向施用器头推动，以迫使来自药筒的药物，从而将预定剂量的药物分配到施用器面上。

公开(公告)号：US20140322331A1

公开(公告)日：2014-10-30

申请号：US14220843

申请日：2014-03-20

Applicant: LEO PHARMA A/S

Inventor： Karsten PETERSSON

IPC: A61K31/592 ,  A61K45/06 ,  A61K9/06 ,  C07C35/21

CPC classification number: A61K31/592 ,  A61K9/0014 ,  A61K9/06 ,  A61K9/146 ,  A61K31/593 ,  A61K45/06 ,  C07C35/21 ,  Y10T428/2982

Abstract: Calcipotriol monohydrate nanocrystals prepared by the process disclosed herein may be incorporated in a pharmaceutical composition for use in the prevention or treatment of dermal diseases and conditions.

Abstract translation: 通过本文公开的方法制备的卡泊三醇一水合物纳米晶体可以掺入用于预防或治疗皮肤疾病和病症的药物组合物中。

公开(公告)号：US20140272998A1

公开(公告)日：2014-09-18

申请号：US14232806

申请日：2012-07-13

Applicant: Ulrik Ralfkiaer ,  Peter Hagedorn ,  Charlotte Busch Ahler ,  Carsten Geisler ,  Anders Woetmann ,  Lone Skov ,  Niels Feentved Odum ,  Elisabeth Ralfkiaer

Inventor： Ulrik Ralfkiaer ,  Peter Hagedorn ,  Charlotte Busch Ahler ,  Carsten Geisler ,  Anders Woetmann ,  Lone Skov ,  Niels Feentved Odum ,  Elisabeth Ralfkiaer

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q2600/158 ,  C12Q2600/178

Abstract: The present invention relates to the field of cancer-diagnostics. In particular the invention relates to a microRNA expression signature that allows discriminating skin samples of cutaneous T-cell lymphomas (CTCL) from non-malignant (inflammantory) skin samples by use of quantitative polymerase chain reaction performed on reverse transcribed miRNA. miR-155, miR-326, miR-663b, miR-203 and miR-205 are shown to be differentially expressed.

Abstract translation: 本发明涉及癌症诊断领域。 特别地，本发明涉及通过使用对逆转录miRNA进行的定量聚合酶链反应，允许从非恶性（炎症性）皮肤样品鉴别皮肤T细胞淋巴瘤（CTCL）的皮肤样品的微小RNA表达特征。 miR-155，miR-326，miR-663b，miR-203和miR-205显示出差异表达。

公开(公告)号：US20130267516A1

公开(公告)日：2013-10-10

申请号：US13989440

申请日：2011-11-21

Applicant: Kristoffer Månsson ,  Lars Kristian Albert Blæhr

Inventor： Kristoffer Månsson ,  Lars Kristian Albert Blæhr

IPC: C07D405/12 ,  C07D213/75 ,  C07D401/04 ,  C07D295/125 ,  C07D239/42

CPC classification number: C07D405/12 ,  C07D213/61 ,  C07D213/74 ,  C07D213/75 ,  C07D239/38 ,  C07D239/42 ,  C07D295/125 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04

Abstract: Compounds of general formula I, (formula [I)], their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, and methods of treating diseases with said compounds.

Abstract translation: 通式I（式[I]]的化合物，它们作为钙受体活性化合物用于预防，治疗或改善生理障碍或与CaSR活性紊乱相关的疾病（例如甲状旁腺机能亢进），包含所述化合物的药物组合物， 以及用所述化合物治疗疾病的方法。