公开(公告)号：WO1998004528A2

公开(公告)日：1998-02-05

申请号：PCT/US1997013248

申请日：1997-07-29

Applicant: BAYER CORPORATION ,  BAYER AKTIENGESELLSCHAFT

Inventor： BAYER CORPORATION ,  BAYER AKTIENGESELLSCHAFT ,  SCHMIDT, Gunter ,  ANGERBAUER, Rolf ,  BRANDES, Arndt ,  MULLER-GLIEMANN, Matthias ,  BISCHOFF, Hilmar ,  SCHMIDT, Delf ,  WOHLFEIL, Stefan ,  SCHOEN, William, R. ,  LADOUCEUR, Gaetan, H. ,  COOK, James, H., II ,  LEASE, Timothy, G. ,  WOLANIN, Donald, J. ,  KRAMSS, Richard, H. ,  HERTZOG, Donald, L. ,  OSTERHOUT, Martin, H.

IPC: C07D213/20

CPC classification number: C07D213/30 ,  C07D213/32 ,  C07D213/34 ,  C07D213/38 ,  C07D213/50 ,  C07D213/55 ,  C07D213/64 ,  C07D213/70 ,  C07D213/74 ,  C07D213/80 ,  C07D215/14 ,  C07D221/04 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D411/12 ,  C07D413/06 ,  C07D413/12 ,  C07D417/12 ,  C07D487/04 ,  C07F7/1804

Abstract: Substituted pyridines of formula (IA) are produced by reaction of suitably substituted pyridylaldehydes with Grignard or Witting reagents, and the resulting products are appropriately reduced. The pyridines of formula (IA) are suitable as active compounds in pharmaceutical products, particularly in pharmaceutical products for the inhibition of cholesterol ester transfer proteins. 3-Heteroalkyl-aryl-substituted pyridines of formula (IB) are produced from pyridines which are correspondingly protected at the hydroxy group and correspondingly substituted. The compounds of formula (IB) according to the invention are suitable as active compounds in pharmaceutical products, particularly pharmaceutical products for the treatment of hyperlipoproteinemia. Substituted pyridines and benzenes of formula (IC) are produced by procedures disclosed herein, and are useful as active ingredients in pharmaceutical products, particularly pharmaceutical products for inhibition of the glucagon receptor, leading to treatment of glucagon-mediated conditions such as diabetes.

Abstract translation: 式（IA）的取代的吡啶通过适当取代的吡啶基醛与格氏试剂或Witting试剂的反应制备，所得产物适当地还原。 式（IA）的吡啶适合作为药物产品中的活性化合物，特别是用于抑制胆固醇酯转移蛋白的药物。 式（IB）的3-杂芳烷基 - 芳基取代的吡啶由吡啶制备，其相应地被羟基保护并相应地被取代。 根据本发明的式（IB）化合物适合作为药物产品中的活性化合物，特别是用于治疗高脂蛋白血症的药物。 通过本文公开的方法制备式（IC）的取代的吡啶和苯，并且可用作药物产品中的活性成分，特别是用于抑制胰高血糖素受体的药物产品，导致治疗胰高血糖素介导的病症如糖尿病。

公开(公告)号：WO1997001764A1

公开(公告)日：1997-01-16

申请号：PCT/US1995008101

申请日：1995-06-27

Applicant: BAYER CORPORATION

Inventor： BAYER CORPORATION ,  REVELLE, David, J. ,  PASTECKI, Peter, A. ,  REITER, Thomas, C.

IPC: G01N35/04

CPC classification number: A61J3/005 ,  B65G47/1492 ,  B65G2201/027

Abstract: An apparatus (10) for orienting and loading solid compact medicaments, such as solid compact medicaments (A), into a carrier device (C) comprises a feeder (12) having a plurality of elongated first channels (20) through which the solid compact medicaments travel with an acute angle relative to a predetermined orientation of the carrier device (C). An orienting member (32) cooperating with the feeder (12) reorients the solid compact medicaments to the predetermined orientation as they exit the feeder (12). In an alternative embodiment, a pitch changing means (42) in fluid communications with the orienting means (32) provides for final orientation of the solid compact medicaments prior to loading in the carrier device (C).

Abstract translation: 用于将固体致密药物（例如固体致密药物（A））定向和装载到载体装置（C）中的装置（10）包括具有多个细长的第一通道（20）的进料器（12），固体致密体 药物相对于载体装置（C）的预定方向以锐角行进。 与进料器（12）配合的取向件（32）在出口给料器（12）时将固体紧凑型药物重新定向至预定取向。 在替代实施例中，与定向装置（32）流体连通的间距改变装置（42）在装载到载体装置（C）之前提供固体紧凑型药物的最终取向。

公开(公告)号：WO1996009317A1

公开(公告)日：1996-03-28

申请号：PCT/US1995011902

申请日：1995-09-19

Applicant: BAYER CORPORATION

Inventor： BAYER CORPORATION ,  KNOWLES, William, J. ,  GURALSKI, Donna ,  LETSINGER, John, T. ,  HAIGH, Wallace ,  HART, John, T. ,  CLAIRMONT, Kevin, B.

IPC: C07H21/04

CPC classification number: G01N33/573 ,  C07K16/40 ,  C12N9/48 ,  C12Q1/37 ,  G01N2333/8103

Abstract: An aminopeptidase which cleaves insulin has been purified from GLUT-4-containing vesicles and cloned. The peptidase has a measured mass of approximately 165 kD, but is 110 kD in its deglycosylated state. It has a predicted mass of 117,239 Daltons based on the amino acid sequence predicted from the cDNA of the figure (SEQ ID NOs: 15 and 16). It includes peptides having the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala (SEQ ID NO: 1) and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Met (SEQ ID NO: 2), and binds with antibodies produced against the peptide identified as (SEQ ID NO: 1). Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.

Abstract translation: 切割胰岛素的氨基肽酶已从含GLUT-4的囊泡中纯化并克隆。 肽酶具有约165kD的测量质量，但其脱糖基化状态为110kD。 基于从图中的cDNA预测的氨基酸序列（SEQ ID NO：15和16），其具有117,239道尔顿的预测质量。 它包括具有氨基酸序列Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala（SEQ ID NO：1）和Ile-Leu-Gln-Asn-Gln-Ile-Gln -Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Met（SEQ ID NO：2），并与针对鉴定为（SEQ ID NO：1）的肽产生的抗体结合。 还要求保护氨基肽酶活性的调节剂和通过施用这种调节剂治疗胰岛素抵抗综合征（包括糖尿病）的方法。

公开(公告)号：WO1998029359A1

公开(公告)日：1998-07-09

申请号：PCT/US1997023111

申请日：1997-12-11

Applicant: BAYER CORPORATION

Inventor： BAYER CORPORATION ,  MARKUSCH, Peter, H. ,  CLINE, Robert, L.

IPC: C05G03/00

CPC classification number: C08G18/5024 ,  C05G3/0029

Abstract: This invention relates to a process for the production of polyurea encapsulated fertilizer particles. These are produced by applying an isocyanate-reactive component which contains at least two amine groups to fertilizer particles to form amine coated particles, and applying a polyisocyanate component to the amine coated particles to form polyurea coated particles. Theses steps may optionally be repeated in successive order. The resultant polyurea encapsulated fertilizer particles contain from about 0.5 to 15 % by weight of polyurea, based on the total weight of the encapsulated fertilizer particles. Instead of using an amine group containing isocyanate-reactive component, water can be applied first.

Abstract translation: 本发明涉及一种生产聚脲包封肥料颗粒的方法。 这些是通过将含有至少两个胺基的异氰酸酯反应性组分施用于肥料颗粒以形成胺包被的颗粒并将多异氰酸酯组分施加到胺涂覆的颗粒上以形成聚脲涂覆的颗粒来制备的。 这些步骤可以可选地以连续的顺序重复。 基于所包封的肥料颗粒的总重量，所得聚脲包封的肥料颗粒含有约0.5至15重量％的聚脲。 代替使用含有异氰酸酯反应性组分的胺基，可以首先施加水。

公开(公告)号：WO1997043247A1

公开(公告)日：1997-11-20

申请号：PCT/US1997007919

申请日：1997-05-12

Applicant: BAYER CORPORATION ,  WOLANIN, Donald, J.

Inventor： BAYER CORPORATION

IPC: C07C235/84

CPC classification number: C07D295/192 ,  C07C17/16 ,  C07C45/46 ,  C07C59/88 ,  C07C69/738 ,  C07C235/84 ,  C07C25/02 ,  C07C49/813

Abstract: Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have generalized formula (I), wherein R is a substituted phenylethyl moiety. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combatting conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from athrosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.

Abstract translation: 提出了基质金属蛋白酶抑制化合物，其药物组合物和使用这些化合物的疾病治疗方法。 本发明的化合物具有通式（I），其中R 25是取代的苯乙基部分。 这些化合物可用于抑制基质金属蛋白酶，因此可用于促进MMP的作用，如骨关节炎，类风湿性关节炎，脓毒性关节炎，牙周病，角膜溃疡，蛋白尿，动脉瘤性主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症的病症 反应，MMP活性介导的骨质减少，颞下颌关节疾病，神经系统脱髓鞘疾病，创伤性关节损伤后的肿瘤转移或退行性软骨损失，以及来自动脉粥样硬化斑块破裂的冠状动脉血栓形成。 本发明还提供了用于治疗这些病症的药物组合物和方法。

公开(公告)号：WO1997043239A1

公开(公告)日：1997-11-20

申请号：PCT/US1997007976

申请日：1997-05-12

Applicant: BAYER CORPORATION ,  VAN ZANDT, Michael, C. ,  BRITTELLI, David, R. ,  DIXON, Brian, R.

Inventor： BAYER CORPORATION

IPC: C07C59/90

CPC classification number: C07D263/44 ,  C07C59/90 ,  C07D237/32 ,  C07D243/24 ,  C07D253/04 ,  C07D263/58 ,  C07D275/04 ,  C07D277/34

Abstract: Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have generalized formula (1) wherein r is 0-2, T is selected from (a) and (b) and R is a mono- or bi-heterocyclic structure. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis of degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from athrosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.

Abstract translation: 提出了基质金属蛋白酶抑制化合物，其药物组合物和使用这些化合物的疾病治疗方法。 本发明的化合物具有通式（1），其中r为0-2，T选自（a）和（b），R 40为单或双杂环结构。 这些化合物可用于抑制基质金属蛋白酶，因此可用于抗MMP的作用，例如骨关节炎，类风湿性关节炎，脓毒性关节炎，牙周病，角膜溃疡，蛋白尿，动脉瘤性主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症的病症 反应，由MMP活性介导的骨质减少，下颌关节疾病，神经系统脱髓鞘疾病，创伤性关节损伤后退行性软骨损失的肿瘤转移，以及来自动脉粥样硬化斑块破裂的冠状动脉血栓形成。 本发明还提供了用于治疗这些病症的药物组合物和方法。

公开(公告)号：WO1997043238A1

公开(公告)日：1997-11-20

申请号：PCT/US1997007975

申请日：1997-05-12

Applicant: BAYER CORPORATION ,  DIXON, Brian, R. ,  CHEN, Jinshan ,  VAN ZANDT, Michael ,  BRITTELLI, David, R.

Inventor： BAYER CORPORATION

IPC: C07C59/90

CPC classification number: C07D209/48 ,  C07C59/90 ,  C07D253/08

Abstract: The present invention provides pharmaceutical compositions and methods for treating certain conditions comprising administering an amount of a compound or composition of the invention which is effective to inhibit the activity of at least one matrix metalloprotease, resulting in achievement of the desired effect. The compounds of the present invention are either of generalized formula (I) wherein y is 0, 2, or 3, r is 0-6, Z is (CH2)7 or (CH2)e-C6H4-(CH2)f, wherein e is 0-1 and f is 1-6, and R is -H, -Cl, -OMe or (a), (b) wherein n is 0-4, R is C2H5, allyl, benzyl, and R is (c) wherein t is 0-1, x is 0-4, and R is one of the following: halide, alkyl of 1-6 carbons, OR, NR2, NO2 (R = H or alkyl of 1-6 carbons). These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from atherosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.

Abstract translation: 本发明提供用于治疗某些病症的药物组合物和方法，包括给予一定量的有效抑制至少一种基质金属蛋白酶活性的本发明化合物或组合物，从而达到预期的效果。 本发明的化合物是通式（I），其中y是0,2或3，r是0-6，Z是（CH 2）7或（CH 2）e -C 6 H 4 - （CH 2）f，其中 e为0-1且f为1-6，R 15为-H，-Cl，-OMe或（a），（b）其中n为0-4，R 17为C 2 H 5，烯丙基， 苄基，R 16是（c）其中t是0-1，x是0-4，R 4是以下之一：卤素，1-6个碳的烷基，OR，NR 2，NO 2（ R = H或1-6个碳的烷基）。 这些化合物可用于抑制基质金属蛋白酶，因此可用于抗MMP的作用，例如骨关节炎，类风湿性关节炎，脓毒性关节炎，牙周病，角膜溃疡，蛋白尿，动脉瘤性主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症的病症 反应，由MMP活性介导的骨质减少，颞下颌关节病，神经系统脱髓鞘疾病，创伤性关节损伤后的肿瘤转移或退行性软骨损失以及来自动脉粥样硬化斑块破裂的冠状动脉血栓形成。 本发明还提供了用于治疗这些病症的药物组合物和方法。

公开(公告)号：WO1996020972A2

公开(公告)日：1996-07-11

申请号：PCT/US1995016244

申请日：1995-12-08

Applicant: BAYER CORPORATION

Inventor： BAYER CORPORATION ,  KRATZ, Mark, R. ,  YEATER, Robert, P. ,  BALISTER, David, A. ,  TIRPAK, Robin, E. ,  NEWMAN, Lewis, S. ,  STEITLE, Richard, B. ,  SOLOMON, Mark, S. ,  TIMM, Ronald, B.

IPC: C08G65/30

CPC classification number: C08G65/30

Abstract: A process for removing a pH-basic material from a polyether polyol polymerizate in which a polymerizate containing polyether and an alkaline material is combined with water and, if the difference between the specific gravity of the poymerizate and water is less than 0.1, an inorganic salt at a temperature and under conditions such that an emulsion forms. No organic solvent is required. The emulsion is heated to a temperature of from about 90 to about 150 DEG C. The heated emulsion is then passed through a coalescing medium at a rate such that the residence time is sufficient to separate the emulsion into an aqueous phase containing the pH-basic material and an organic phase containing a polyether polyol which is substantially free of pH-basic material.

Abstract translation: 从聚醚多元醇聚合物中除去含有聚醚和碱性物质的聚合物的pH-碱性物质与水混合的方法，如果所述聚合物与水的比重之差小于0.1，则无机盐 在温度和条件下使得形成乳液。 不需要有机溶剂。 将乳液加热至约90至约150℃的温度。然后将加热的乳液以一定的速率通过聚结介质，使得停留时间足以将乳液分离成含有pH-碱性的水相 材料和含有基本上不含pH-碱性材料的聚醚多元醇的有机相。

公开(公告)号：WO1997043237A1

公开(公告)日：1997-11-20

申请号：PCT/US1997007951

申请日：1997-05-12

Applicant: BAYER CORPORATION ,  KLUENDER, Harold, C., E. ,  DIXON, Brian, R. ,  BRITTELLI, David, R.

Inventor： BAYER CORPORATION

IPC: C07C59/84

CPC classification number: C07D209/48 ,  C07C59/84 ,  C07C59/90 ,  C07D237/32 ,  C07D253/04

Abstract: Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have generalized formula (I) wherein R represents C6-C12 alkyl; C5-C12 alkoxy; C5-C12 alkylthio; a polyether of formula R O(C2H4O)a- in which a is 1 or 2 and R is C1-C5 alkyl, phenyl, or benzyl; and substituted alkynyl of formula R (CH2)b-CC-; in which b is 1-10 and R is H-, HO-, or R O- in which R is C1-C3 alkyl, phenyl, or benzyl. The alkyl, phenyl, and benzyl portions of R may bear at least one pharmaceutically-acceptable substituent. The subscript n is 2-4. R represents phenyl; imidoyl of 4-12 carbon atoms; (3H)-benzo-1,2,3-triazin-4-on-3-yl; N-saccharinyl; (2H)-phthalazin-1-on-2-yl; 2-benzoxazolin-2-on-3-yl; 5,5-dimethyloxazolidine-2,4-dion-3-yl; and thiazolidine-2,4-dion-3-yl; with the phenyl and benzo portions of R permissibly bearing at least one pharmaceutically-acceptable substituent. Pharmaceutically acceptable salts of these materials are also included.

Abstract translation: 基质金属蛋白酶抑制剂，含有它们的药物组合物，以及使用它们治疗各种生理条件的方法。 本发明的化合物具有通式（I），其中R 1表示C 6 -C 12烷基; C5-C12烷氧基; C5-C12烷硫基; 式R 2 O（C 2 H 4 O）a - 的聚醚，其中a为1或2，R 2为C 1 -C 5烷基，苯基或苄基; 和取代的式R 3（CH 2）b-CC-的炔基; 其中b为1-10，R 3为H，HO-或R 4 O-，其中R 4为C 1 -C 3烷基，苯基或苄基。 R 1的烷基，苯基和苄基部分可以具有至少一个药学上可接受的取代基。 下标n为2-4。 R 5表示苯基; 4-12个碳原子的亚氨基; （3H） - 苯并-1,2,3-三嗪-4-上-3-基; 的N- saccharinyl; （2H）-2,3-二氮杂萘-1-酮-2-基; 2-苯并恶唑啉-2-酮-3-基; 5,5-二甲基唑烷-2,4-二酮-3-基; 和噻唑烷-2,4-二酮-3-基; 其中R 5的苯基和苯并部分允许具有至少一个药学上可接受的取代基。 也包括这些材料的药学上可接受的盐。

公开(公告)号：WO1996039146A1

公开(公告)日：1996-12-12

申请号：PCT/US1996008864

申请日：1996-06-05

Applicant: BAYER CORPORATION

Inventor： BAYER CORPORATION ,  PURWAR, Shivaji ,  GOLDMAN, David

IPC: A61K31/56

CPC classification number: A61K9/0046 ,  A61K9/0014 ,  A61K9/10 ,  A61K31/57 ,  A61K47/32 ,  A61K31/495 ,  A61K2300/00

Abstract: Compositions for introduction, preferably by instillation, into human and animal ears, and a method, for the treatment of otitis externa and otitis media, especially otorrhea. The compositions are non-ototoxic, non-irritating and non-sensitizing. The compositions are aqueous based and contain ciprofloxacin and optionally hydrocortisone.

Abstract translation: 用于引入的组合物，优选通过滴注入人和动物耳朵，以及用于治疗外耳炎和中耳炎尤其是耳痛的方法。 组合物是非耳毒性的，无刺激性的和非致敏性的。 组合物是基于水的，并且含有环丙沙星和任选的氢化可的松。