TWI524894B - Ｄｐｐ ｉｖ抑制劑之用途 - Google Patents

Ｄｐｐ ｉｖ抑制劑之用途 Download PDF

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TWI524894B
TWI524894B TW103119144A TW103119144A TWI524894B TW I524894 B TWI524894 B TW I524894B TW 103119144 A TW103119144 A TW 103119144A TW 103119144 A TW103119144 A TW 103119144A TW I524894 B TWI524894 B TW I524894B
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dpp
diabetes
combination
inhibitor
glucose
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都基 克勞斯
欣梅爾斯巴齊 法蘭克
馬克 麥可
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百靈佳殷格翰國際股份有限公司
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Description

DPP IV抑制劑之用途
本說明書描述選定DPP IV抑制劑用於治療生理功能性病症及於降低處於危險中之患者群出現該等功能性病症之風險的用途。此外，本說明書描述上述DPP IV抑制劑聯合其他活性物質之用途，藉此可達成經改良之治療結果。此等應用可用以製備相應藥劑。
亦稱為CD26之酶DPP-IV為促進在N末端具有脯胺酸或丙胺酸基團之蛋白質中二肽裂解之絲胺酸蛋白酶。DPP-IV抑制劑藉此影響生物活性肽(包括肽GLP-1)之血漿含量且為用於治療糖尿病之極具價值的分子。
主要發生在30歲以下之青少年之第一型糖尿病歸類為自身免疫疾病。在相應遺傳素因下及在多種因素影響下，出現胰島炎，隨後破壞B細胞，以使得胰腺不再能產生大量胰島素(若能產生)。
第二型糖尿病並不歸類為自身免疫疾病且本身顯示空腹血糖含量超過每分升血漿125毫克葡萄糖；血糖值之量測為常規醫學分析中之標準程序。若空腹血糖含量超過每分升血漿99毫克葡萄糖之最大正常含量，但不超過每分升血漿125毫克葡萄糖之臨限值，則疑為糖尿病前期，其與糖尿病有關。此亦稱為病理性空腹葡萄糖(空腹葡萄糖異常)。糖尿病前期之另一徵象為葡萄糖耐受性異常，亦即在口服葡萄糖耐受性測試範疇內在空腹攝取75毫克葡萄糖後2小時血糖含量為 每分升血漿140-199毫克葡萄糖。
若進行葡糖耐受性測試，則空腹攝取75公克葡萄糖後2小時，糖尿病患者之血糖含量將超過每分升血漿199毫克葡萄糖。在葡萄糖耐受性測試中，在空腹10-12小時之後向測試患者經口投與75公克葡萄糖且在即將攝取葡萄糖之前及在攝取葡萄糖之後1及2小時記錄血糖含量。在健康受檢者體內，血糖含量在攝取葡萄糖之前應介於每分升血漿60毫克與99毫克之間，在攝取葡萄糖之後1小時小於每分升200毫克且在2小時之後小於每分升140毫克。若在2小時之後，該值介於140毫克與199毫克之間，則將其視為葡萄糖耐受性異常或在某些狀況下視為葡萄糖不耐症。
在監測糖尿病之治療時，血紅蛋白B鏈之非酶促糖化產物，HbA1c值尤其重要。由於其形成主要視血糖含量及紅血球壽命而定，因此HbA1c在"血糖記憶"意義上反映先前4-12週之平均血糖含量。HbA1c含量已受較強化糖尿病治療良好控制較長時間(亦即試樣中總血紅蛋白<6.5%)之糖尿病患者受到顯著較好之保護而免於糖尿病微血管病變。糖尿病之有效治療可給予糖尿病患者HbA1c含量約1.0%-1.5%之平均改善。此HbA1C含量降低並不足以使所有糖尿病患者處於<6.5%且較佳<6% HbA1c之所要目標範圍內。
若可偵測到胰島素抗性，則此為存在糖尿病前期之複合代謝病症之尤其有力的徵象。因此，可能為維持葡萄糖體內平衡，某人需要多達他人2-3倍之胰島素。測定胰島素抗性之最可靠方法為正常葡萄糖血症-高胰島素血症夾鉗測試(euglycaemic-hyperinsulinaemic clamp test)。胰島素與葡萄糖之比率係在經組合之胰島素-葡萄糖輸注技術之範疇內測定。若葡萄糖吸收低於所探查背景群體之25個百分點，則存在胰島素抗性(WHO定義)。與夾鉗測試相比頗不費勁者為所謂的最小模型，其中在靜脈葡萄糖耐受性測試期間，血液中之胰島素及葡萄 糖濃度係以固定時間間隔量測且由此計算胰島素抗性。另一種量測方法為數學HOMA模型。胰島素抗性係藉助於空腹血漿血糖濃度及空腹胰島素濃度來計算。在此方法中，不可能區別肝臟胰島素抗性與周邊胰島素抗性。此等方法並不真正適於在日常實踐中評估胰島素抗性。通常，日常臨床實踐中使用其他參數來評估胰島素抗性。較佳地，例如，使用患者之甘油三酯濃度，此係由於甘油三酯含量增加與存在胰島素抗性顯著相關。
為略微簡化，實務上假定若某人具有以下特徵中之至少2者，則其具有胰島素抗性：
1)超重或肥胖
2)高血壓
3)血脂異常(血液中總脂質含量改變)
4)至少一位已經確診葡萄糖耐受性異常或第二型糖尿病之近親。
超重意謂在體重指數(BMI)介於25kg/m2與30kg/m2之間的此情況下，BMI為體重(公斤)與身高(公尺)之平方的商。在顯性肥胖症中，BMI為30kg/m2或更高。
根據上述胰島素抗性之定義，直接可見若發現患者患有高血壓，則降血壓劑適合且指定用於治療胰島素抗性。
糖尿病前期之類似徵象為是否滿足代謝症候群之病狀，其主要特點為胰島素抗性。根據ATP IHINCEP準則(Journal of the American Medical Association 285：2486-2497,2001中之Executive Summary of the Third Report of the National Cholesterol Education Program(NCEP))，若患者具有以下特徵中之至少3者，則存在代謝症候群：
1)腹部肥胖，定義為男性腰身>40吋或102公分且女性>35吋或94公分
2)甘油三酯含量>150毫克/分升
3)男性之HDL-膽固醇含量<40毫克/分升
4)高血壓>130/>85mm Hg
5)空腹血糖>110毫克/分升。
此代謝症候群之定義直接展示若發現患者患有高血壓，則降血壓劑適於治療代謝症候群。
甘油三酯血液含量超過150毫克/分升亦指示存在糖尿病前期。此推測係由HDL膽固醇之低血液含量來證實。在女性體內，低於每分升血漿55毫克之含量視為過低，而在男性體內，低於每分升血漿45毫克之含量視為過低。血液中甘油三酯及HDL膽固醇亦可藉由醫學分析中之標準方法來測定且例如描述於Thomas L(編者)："Labor und Diagnose",TH-Books mbH,Frankfurt Main 2000中。若空腹血糖含量亦超過每分升血漿99毫克葡萄糖，則糖尿病前期之推測進一步得以證實。
術語妊娠性糖尿病(妊娠糖尿病)表示在妊娠期間發展且通常在分娩之後又立即停止的一種糖疾病形式。妊娠性糖尿病係藉由在妊娠第24週與第28週之間進行的篩檢測試來確診。其通常為在投與50公克葡萄糖溶液之後一小時量測血糖含量之簡單測試。若此1h含量超過140毫克/分升，則疑為妊娠性糖尿病。可藉由用75公克葡萄糖之標準葡萄糖耐受性測試來獲得最終確認。
高血糖症描述在空腹狀態下(與<100毫克/分升之正常含量相比，100-125毫克/分升之高葡萄糖含量或>125毫克/分升之糖尿病性-高血糖含量)或在非空腹狀態下(>180毫克/分升之高葡萄糖含量)，在血液中量測到極高葡萄糖含量的功能性病症。
臨床醫師對於腎上腺素激導性餐後徵候群(反應性低血糖)意謂不相稱之高胰島素含量導致由在餐後快速消化之糖類與持續高胰島素含量之間的不平衡所引起之血糖含量下降(低血糖)的功能性病症。
術語糖尿病足係指由糖尿病引起之足上病變，其主要原因為可歸因於不充分代謝控制之多發性神經病。糖尿病足係藉由在現有糖尿病情況下出現典型病變(例如潰瘍)來確診。
術語糖尿病相關潰瘍係指糖尿病患者之潰瘍性發炎性皮膚缺陷。糖尿病相關潰瘍係藉由典型既往病歷及身體檢查(例如檢查足)來確診。
若糖尿病患者遭受總膽固醇增加或更通常在糖尿病性高脂質血症中血漿甘油三酯增加，伴以或不伴以HDL膽固醇降低，則使用術語糖尿病性高脂質血症。
若總膽固醇並不升高，但HDL-膽固醇及LDL-膽固醇之分佈改變，亦即患者之HDL膽固醇含量過低(例如女性<55毫克/分升及男性<45毫克分升)，則使用術語糖尿病性血脂異常。
若主觀症狀或客觀檢查表明心臟不能達成必要的射血輸出，則使用術語心臟衰竭。主觀症狀可為例如在受力狀態下或在靜止狀態下呼吸困難。客觀檢查包括根據超音之心臟之射血輸出減少(射血量減少)、根據X射線之肺充血，及/或步行距離減少。
一些選定DPP IV抑制劑尤其適於製備供治療性處理已經確診患有選自下列病症之醫學或生理功能性病症的患者之藥劑：糖尿病前期、葡萄糖不耐症(葡萄糖耐受性異常)、病理性空腹葡萄糖(空腹葡萄糖異常)、糖尿病足、糖尿病相關潰瘍、糖尿病性高脂質血症、糖尿病性血脂異常、最新診斷之第一型糖尿病(以維持胰島素自胰腺之殘餘分泌)、妊娠性糖尿病(妊娠糖尿病)、高血糖症、腎上腺素激導性餐後徵候群(反應性低血糖)或心臟衰竭。
此等藥劑亦可用以降低如下風險：儘管進行治療，患者仍會遭受葡萄糖代謝異常、HbA1c值升高、空腹葡萄糖值異常、顯性第二型糖尿病、糖尿病足、糖尿病相關潰瘍、糖尿病性高脂質血症或糖尿病 性血脂異常，且儘管有療法，胰島素治療仍會變得必需或會出現大血管併發症。
此類大血管併發症之實例為心肌梗塞、急性冠狀動脈徵候群、不穩定型心絞痛、穩定型心絞痛、出血性中風或缺血性中風、周邊動脈阻塞性疾病、心肌病、左心功能不全、右心功能不全、綜合性心功能不全、心律異常及血管再狹窄。此等大血管併發症為熟習此項技術者已知且詳細描述於標準教科書中。
此外，該等物質適於在蘭格罕氏島(islets of Langerhans)或β細胞移植之後增強細胞之生命力及分泌能力，且藉此確保移植後之有利結果。該等物質亦可在蘭格罕氏島或β細胞之分離及移植階段期間，藉由將指定物質以1nmol/l至1μmol/l之合適濃度，較佳以1nmol/l至100nmol/l之濃度添加至習知分離或儲存介質中來使用。此使得待移植物質之品質改良。品質改良尤其係與GLP-1(胰高血糖素樣肽1)之量增加(較佳以1-100nmol/l之濃度)組合獲得。本發明之另一目標為相應分離或儲存介質及藉由將DPP IV抑制劑添加至所用介質中來增強蘭格罕氏島或β細胞之生命力及分泌能力的相應方法。
最後，上述抑制劑適於治療多種形式之關節炎，但尤其為類風濕性關節炎。
本發明之選定DPP IV抑制劑可由
或式(II)來描述 其中R1表示([1,5]萘啶-2-基)甲基、(喹唑啉-2-基)甲基、(喹喏啉-6-基)甲基、(4-甲基-喹唑啉-2-基)甲基、2-氰基-苄基、(3-氰基-喹啉-2-基)甲基、(3-氰基-吡啶-2-基)甲基、(4-甲基-嘧啶-2-基)甲基或(4,6-二甲基-嘧啶-2-基)甲基且R2表示3-(R)-胺基-哌啶-1-基、(2-胺基-2-甲基-丙基)-甲基胺基或(2-(S)-胺基-丙基)-甲基胺基。
尤其較佳之DPP IV抑制劑為以下化合物及其治療活性鹽：1-[(4-甲基-喹唑啉-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-(3-(R)-胺基-哌啶-1-基)-黃嘌呤(參看WO 2004/018468，實例2(142))：
1-[([1,5]萘啶-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2004/018468，實例2(252))：
1-[(喹唑啉-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2004/018468，實例2(80))：
2-((R)-3-胺基-哌啶-1-基)-3-(丁-2-炔基)-5-(4-甲基-喹唑啉-2-基甲基)-3,5-二氫-咪唑幷[4,5-d]噠嗪-4-酮(參看WO 2004/050658，實例136)：
1-[(4-甲基-喹唑啉-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-[(2-胺基-2-甲基-丙基)-甲基胺基]-黃嘌呤(參看WO 2006/029769，實例2(1))：
1-[(3-氰基-喹啉-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2005/085246，實例1(30))：
1-(2-氰基-苄基)-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2005/085246，實例1(39))：
1-[(4-甲基-喹唑啉-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-[(S)-(2-胺基-丙基)-甲基胺基]-黃嘌呤(參看WO 2006/029769，實例2(4))：
1-[(3-氰基-吡啶-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2005/085246，實例1(52))：
1-[(4-甲基-嘧啶-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2005/085246，實例1(81))：
1-[(4,6-二甲基-嘧啶-2-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2005/085246，實例1(82))：
1-[(喹喏啉-6-基)甲基]-3-甲基-7-(2-丁炔-1-基)-8-((R)-3-胺基-哌啶-1-基)-黃嘌呤(參看WO 2005/085246，實例1(83))：
此等DPP IV抑制劑不同於結構上類似之DPP IV抑制劑，此係由於當其與其他醫藥活性物質組合時，其將特殊效能及持久作用與有利藥理特性、受體選擇性及有利副作用概況組合或產生出乎意料之治療優點或改良。其製備揭示於所提及之公開案中。
由於不同代謝功能性病症常同時出現，因此往往指定組合許多彼此不同之活性成份。因此，視所確診之功能性病症而定，若DPP IV抑制劑與選自其他抗糖尿病物質之活性物質，尤其降低血液中血糖含量或脂質含量、升高血液中HDL含量、降低血壓或指定用於治療動脈粥樣硬化或肥胖之活性物質組合，則可獲得經改良之治療結果。
當靜脈內投與時，DPP IV抑制劑之所需劑量為0.1mg至10mg，較佳0.25mg至5mg，且當經口投與時為0.5mg至100mg，較佳2.5mg至50mg，在各種情況下每天1至4次。為達成此目的，視情況與另一種活性物質組合之化合物可與一或多種習知惰性載劑及/或稀釋劑一起，例如與玉米澱粉、乳糖、葡萄糖、微晶纖維素、硬脂酸鎂、聚乙烯吡咯啶酮、檸檬酸、酒石酸、水、水/乙醇、水/甘油、水/山梨糖醇、水/聚乙二醇、丙二醇、十六十八醇(cetylstearylalcohol)、羧甲基纖維素或諸如硬脂之脂質或其合適混合物一起調配，以形成習知蓋倫製劑(galenic preparation)，諸如錠劑、包衣錠劑、膠囊、散劑、懸浮液或栓劑。
因此本發明之DPP IV抑制劑係由熟習此項技術者使用如先前技術中所述之容許調配物賦形劑來製備。該等賦形劑之實例為稀釋劑、黏合劑、載劑、填充劑、潤滑劑、流動劑、結晶遲延劑、崩解劑、溶解劑、著色劑、pH值調節劑、界面活性劑及乳化劑。
合適稀釋劑之實例包括纖維素粉末、磷酸氫鈣、赤藻糖醇、(低取代)羥丙基纖維素、甘露糖醇、預膠化澱粉或木糖醇。
合適黏合劑之實例包括乙烯吡咯啶酮與其他乙烯基衍生物之共聚物(共聚乙烯吡咯酮)、羥丙基甲基纖維素(HPMC)、羥丙基纖維素(HPC)、聚乙烯吡咯啶酮(聚維酮(povidone))、預膠化澱粉或低取代羥丙基纖維素。
合適潤滑劑之實例包括滑石粉、聚乙二醇、蘿酸鈣、硬脂酸鈣、氫化蓖麻油或硬脂酸鎂。
合適崩解劑之實例包括玉米澱粉或交聯聚乙烯吡咯酮。
製備本發明之DPP IV抑制劑之醫藥調配物的合適方法為：將與合適之製錠賦形劑呈粉末混合物形式之活性物質直接製錠； 與合適之賦形劑一起粒化且隨後與合適之賦形劑混合且隨後製錠以及薄膜包衣；或將粉末混合物或顆粒填充至膠囊中。
合適之粒化方法為
在強力混合器中濕式粒化，隨後流化床乾燥；一鍋式粒化；流化床粒化；或與合適之賦形劑一起乾式粒化(例如藉由滾筒壓製)且隨後製錠或填充至膠囊中。
上述DPP IV抑制劑亦可與其他活性物質聯合使用，藉此可獲得經改良之治療結果。該組合治療可以該等物質之自由組合形式或以固定組合形式，例如以錠劑或膠囊形式給予。為達成此目的所需之組合搭配物之醫藥調配物可以醫藥組合物形式購得或可由熟習此項技術者使用習知方法調配。可以醫藥組合物形式購得之活性物質於先前技術中多處加以描述，例如每年出版之藥物目錄，製藥工業聯合會之"Rote Liste®"中，或每年更新之稱為"Physicians' Desk Reference"之處方藥物有關製造商資訊的彙編。
抗糖尿病藥組合搭配物之實例為二甲雙胍；磺醯基脲，諸如格列本脲(glibenclamide)、甲苯磺丁脲(tolbutamide)、格列美脲(glimepiride)、格列吡嗪(glipizide)、格列喹酮(gliquidon)、格列波脲(glibornuride)及格列齊特(gliclazide)；那格列奈(nateglinide)；瑞格列奈(repaglinide)；噻唑烷二酮，諸如羅格列酮(rosiglitazone)及吡格列酮(pioglitazone)；PPAR γ調節劑，諸如美格利德(metaglidase)；PPAR-γ促效劑，諸如GI 262570；PPAR-γ拮抗劑；PPAR-γ/α調節劑，諸如特沙他唑(tesaglitazar)、莫格他唑(muraglitazar)及KRP297；PPAR-γ/α/δ調節劑；AMPK-活化劑，諸如AICAR；乙醯輔酶A羧化酶 (ACC1及ACC2)抑制劑；二醯甘油-乙醯轉移酶(DGAT)抑制劑；胰腺β細胞GCRP促效劑，諸如SMT3-受體促效劑及GPR119；11β-HSD抑制劑；FGF19促效劑或類似物；α-葡糖苷酶阻斷劑，諸如阿卡波糖(acarbose)、伏格列波糖(voglibose)及米格列醇(miglitol)；α2-拮抗劑；胰島素及胰島素類似物，諸如人類胰島素、賴脯胰島素(insulin lispro)、胰島素格素林(glusilin)、r-DNA-門冬胰島素(insulinaspart)、NPH胰島素、胰島素迪特美(detemir)、胰島素鋅懸浮液及胰島素加列金(glargin)；胃抑制肽(GIP)；普蘭林肽(pramlintide)；艾汀(amylin)或GLP-1及GLP-1類似物，諸如艾生丁-4(Exendin-4)；SGLT2抑制劑，諸如KGT-1251；蛋白質酪胺酸-磷酸酶之抑制劑；葡萄糖-6-磷酸酶之抑制劑；果糖-1,6-雙磷酸酶調節劑；肝糖磷酸化酶調節劑；胰高血糖素受體拮抗劑；磷酸烯醇丙酮酸羧基激酶(phosphoenolpyruvatecarboxykinase，PEPCK)抑制劑；丙酮酸脫氫酶激酶(PDK)抑制劑；酪胺酸-激酶之抑制劑(50mg至600mg)，諸如PDGF受體-激酶(參看EP A-564409、WO 98/35958、US 5093330、WO 2004/005281及WO 2006/041976)；葡糖激酶/調節蛋白調節劑，包括葡糖激酶活化劑；肝糖合成酶激酶抑制劑；含有SH2-功能部位之2型肌醇5-磷酸酶(SHIP2)；IKK抑制劑，諸如高劑量水楊酸鹽；JNK1抑制劑；蛋白激酶C-θ抑制劑；β3促效劑，諸如瑞妥貝隆(ritobegron)、YM 178、索拉貝隆(solabegron)、塔裏貝隆(talibegron)、N-5984、GRC-1087、拉法貝隆(rafabegron)、FMP825；醛糖還原酶抑制劑，諸如AS 3201、折那司他(zenarestat)、法地司他(fidarestat)、依帕司他(epalrestat)、阮尼司他(ranirestat)、NZ-314、CP-744809及CT-112；SGLT-1或SGLT-2抑制劑；KV 1.3通道抑制劑；GPR40調節劑；SCD-1抑制劑；CCR-2拮抗劑；及其他DPPIV抑制劑。
11β-HSD1抑制劑之實例描述於以下專利中： WO 2007/013929、WO 2007/007688、WO 2007/003521、WO 2006/138508、WO 2006/135795、WO 2006/135667、WO 2006/134481、WO 2006/134467、WO 2006/132436、WO 2006/132197、WO 2006/113261、WO 2006/106423、WO 2006/106052、WO 2006/105127、WO 2006/104280、WO 2006/100502、WO 2006/097337、WO 2006/095822、WO 2006/094633、WO 2006/080533、WO 2006/074330、WO 2006/074244、WO 2006/068992、WO 2006/068991、WO 2006/068199、WO 2006/066109、WO 2006/055752、WO 2006/053024、WO 2006/051662、WO 2006/050908、WO 2006/049952、WO 2006/048750、WO 2006/048331、WO 2006/048330、WO 2006/040329、WO 2006/037501、WO 2006/030805、WO 2006/030804、WO 2006/017542、WO 2006/024628、WO 2006/024627、WO 2006/020598、WO 2006/010546、WO 2006/002349、WO 2006/002350、WO 2006/012173、WO 2006/012227、WO 2006/012226、WO 2006/000371、WO 2005/118538、WO 2005/116002、WO 2005/110992、WO 2005/110980、WO 2005/108359、WO 2005/108361、WO 2005/108360、WO 2005/108368、WO 2005/103023、WO 2005/097764、WO 2005/097759、WO 2005/095350、WO 2005/075471、WO 2005/063247、WO 2005/060963、WO 2005/047250、WO 2005/046685、WO 2005/044192、WO 2005/042513、WO 2005/016877、WO 2004/113310、WO 2004/106294、WO 2004/103980、WO 2004/089896、WO 2004/089380、WO 2004/089471、WO 2004/089470、WO 2004/089367、WO 2005/073200、WO 2004/065351、WO 2004/058741、WO 2004/056745、WO 2004/056744、WO 2004/041264、WO 2004/037251、WO 2004/033427、WO 2004/011410、WO 2003/104208、WO 2003/104207、WO 2003/065983、WO 2003/059267、WO 2003/044009、WO 2003/044000、WO 2003/043999、WO 2002/076435、WO 2001/090094、WO 2001/090093、WO 2001/090092、WO 2001/090091、WO 2001/090090、US 2007/049632、US 2006/148871、US 2006/025445、US 2006/004049、US 2005/277647、US 2005/261302、US 2005/245534、US 2005/245532、US 2005/245533及JP 2005/170939。11β-HSD1抑制劑之代表性實例為以下化合物：
及其鹽。
肝糖磷酸化酶調節劑之實例描述於以下專利中：WO 2006/126695、WO 2006/082401、WO 2006/082400、WO 2006/059165、WO 2006/059164、WO 2006/059163、WO 2006/056815、WO 2006/055463、WO 2006/055462、WO 2006/055435、WO 2006/053274、WO 2006/052722、WO 2005/085245、WO 2005/085194、WO 2005/073231、WO 2005/073230、WO 2005/073229、WO 2005/067932、WO 2005/020987、WO 2005/020986、WO 2005/020985、WO 2005/019172、WO 2005/018637、WO 2005/013981、WO 2005/013975、WO 2005/012244、WO 2004/113345、WO 2004/104001、WO 2004/096768、WO 2004/092158、WO 2004/078743、WO 2004/072060、WO 2004/065356、WO 2004/041780、WO 2004/037233、WO 2004/033416、WO 2004/007455、WO 2004/007437、WO 2003/104188、WO 2003/091213、WO 2003/084923、WO 2003/084922、WO 2003/074532、WO 2003/074531、WO 2003/074517、WO 2003/074513、WO 2003/074485、WO 2003/074484、WO 2003/072570、WO 2003/059910、WO 2003/037864、WO 2002/096864、WO 2002/020530、WO 2001/094300、WO 2000/123347、WO 1996/39384、WO 1996/39385、EP 1391460、EP 1136071、EP 1125580、EP 1088824、EP 0978279、JP 2004196702、US 2004/002495、US 2003/195243及US 5998463。
葡糖激酶活化劑之實例描述於以下專利中：WO 2007/017649、WO 2007/007910、WO 2007/007886、WO 2007/007042、WO 2007/007041、WO 2007/007040、WO 2007/006814、WO 2007/006761、WO 2007/006760、WO 2006/125972、WO 2006/125958、WO 2006/112549、WO 2006/059163、WO 2006/058923、WO 2006/049304、WO 2006/040529、WO 2006/040528、WO 2006/016194、WO 2006/016178、WO 2006/016174、WO 2005/121110、WO 2005/103021、WO 2005/095418、WO 2005/095417、WO 2005/090332、WO 2005/080360、WO 2005/080359、WO 2005/066145、WO 2005/063738、WO 2005/056530、WO 2005/054233、WO 2005/054200、WO 2005/049019、WO 2005/046139、WO 2005/045614、WO 2005/044801、WO 2004/081001、WO 2004/076420、WO 2004/072066、WO 2004/072031、WO 2004/063194、WO 2004/063179、WO 2004/052869、WO 2004/050645、WO 2004/031179、WO 2004/002481、WO 2003/095438、WO 2003/080585、WO 2003/055482、WO 2003/047626、WO 2003/015774、WO 2003/000267、WO 2003/000262、WO 2002/048106、WO 2002/046173、WO 2002/014312、WO 2002/008209、WO 2001/085707、WO 2001/085706、WO 2001/083478、WO 2001/083465、WO 2001/044216及WO 2000/058293。
葡糖激酶活化劑之代表性實例為以下化合物： 其中G1表示環丙基或環丁基且G2表示5-氟-噻唑-2-基、1-甲基-1H-吡唑-3-基或吡嗪-2-基；及 其中G3表示甲基或乙基且G4表示噻唑-2-基、4-甲基-噻唑-2-基、 5-甲基-噻唑-2-基或吡嗪-2-基，及其鹽。
SGLT1或SGLT2抑制劑之實例描述於以下專利中：WO 2006/108842、WO 2006/087997、WO 2006/080577、WO 2006/080421、WO 2006/073197、WO 2006/064033、WO 2006/062224、WO 2006/054629、WO 2006/037537、WO 2006/035796、WO 2006/018150、WO 2006/008038、WO 2006/002912、WO 2006/010557、WO 2006/011502、WO 2006/011469、WO 2005/121161、WO 2005/012326、WO 2005/095429、WO 2005/095372、WO 2005/095373、WO 2005/092877、WO 2005/085267、WO 2005/085265、WO 2005/085237、WO 2005/063785、WO 2005/021566、WO 2005/012243、WO 2005/012242、WO 2005/012326、WO 2005/012318、WO 2005/011592、WO 2004/113359、WO 2004/099230、WO 2004/089967、WO 2004/089966、WO 2004/087727、WO 2004/080990、WO 2004/058790、WO 2004/052903、WO 2004/052902、WO 2004/019958、WO 2004/018491、WO 2004/014932、WO 2004/014931、WO 2004/013118、WO 2003/099836、WO 2003/080635、WO 2003/020737、WO 2003/011880、WO 2003/000712、WO 2002/098893、WO 2002/088157、WO 2002/083066、WO 2002/068440、WO 2002/068439、WO 2002/064606、WO 2002/053573、WO 2002/044192、WO 2002/036602、WO 2002/028872、WO 2001/074835、WO 2001/074834、WO 2001/068660、WO 2001/027128、WO 2001/016147、JP 2005247834、JP 2004359630、JP 2004196788、JP 2003012686及US 2006/063722。
SGLT1或SGLT2抑制劑之代表性實例為以下化合物及其與天然胺 基酸之鹽或錯合物： 其中G5與G8彼此獨立地表示氫、氟、氯、溴、氰基、甲基、乙基、異丙基、二氟甲基、三氟甲基、乙炔基、丙-1-炔-1-基、丁-1-炔-1-基、羥基、甲氧基、乙氧基、二氟甲氧基、環丙氧基、環丁氧基、環戊氧基或環己氧基；且 G6表示氟、氯、甲基、乙基、甲氧基、乙氧基、二氟甲氧基、三氟甲氧基、三甲基矽烷基乙基、乙炔基、2-羥基丙-2-基乙炔基、2-甲氧基丙-2-基乙炔基、3-羥基-1-丙炔-1-基、3-甲氧基-1-丙炔-1- 基、環丙基、環丁基、環戊基、環己基、環丙氧基、環丁氧基、環戊氧基、環己氧基、四氫呋喃-3-基氧基、四氫哌喃-4-基氧基、哌啶-4-基氧基、N-甲基哌啶-4-基氧基及N-乙醯基哌啶-4-基氧基；且 G7表示氫或氟； 其中G表示氟、氯、甲基、乙基、乙炔基、甲氧基、乙氧基、二氟甲氧基、三氟甲氧基、環丁氧基、環戊氧基、3-四氫呋喃基氧基或4-四氫哌喃基氧基； 其中G表示氟、氯、甲基、乙基、乙炔基、甲氧基、乙氧基、二氟甲氧基、三氟甲氧基、環丁氧基、環戊氧基、3-四氫呋喃基氧基或4-四氫哌喃基氧基； 其中G8表示氫、甲氧基羰基或乙氧基羰基，且G9表示氟、氯、甲基、乙基、乙炔基、甲氧基、乙氧基、二氟甲氧基、三氟甲氧基、環丁氧基、環戊氧基、3-四氫呋喃基氧基或4-四氫哌喃基氧基；及 其中：G10表示C1-3烷基或全氟-C1-3烷基；G11表示氫、C1-3烷基或全氟-C1-3烷基；G12表示氟、氯、溴、C1-6烷基、經1至3個氟原子取代之C1-6烷基、C1-6烷氧基、經1至3個氟原子取代之C1-6烷氧基、C1-6烷基硫基、C2-6烯基、C2-6炔基、全氟-C1-3烷基、環丁氧基、環戊氧基、環己氧基、四氫呋喃基氧基或4-四氫哌喃基氧基；且G13與G14彼此獨立地表示氫、氟、氯、溴、C1-6烷基、經1至3個氟原子取代之C1-6烷基、C1-6烷氧基、經1至3個氟原子取代之C1-6烷氧基、C1-6烷基硫基、C2-6烯基、C2-6炔基、全氟-C1-3烷基；且 G15表示氫、C2-20烷醯基、C1-6烷氧基羰基或苯甲醯基。
抗糖尿病藥組合搭配物之一尤其較佳實例為約100mg至500mg或200mg至850mg(一天一至三次)，或約300mg至1000mg一天一次或兩次劑量之二甲雙胍，或約100mg至1000mg或較佳500mg至1000mg一天一或兩次或約500mg至2000mg一天一次劑量之延遲釋放二甲雙胍。另一尤其較佳實例為約1-10mg、15mg、30mg或45mg一天一次劑量之吡格列酮。另一尤其較佳實例為約10mg至50mg或至多100mg一天一至三次劑量之米格列醇。
降低血液中脂質含量之組合搭配物之實例為HMG-CoA還原酶抑制劑，諸如辛伐他汀(simvastatin)、阿托伐他汀(atorvastatin)、洛伐他汀(lovastatin)、氟伐他汀(fluvastatin)、普伐他汀(pravastatin)及羅素他汀(rosuvastatin)；纖維酸酯，諸如苯紮貝特(bezafibrate)、非諾貝特(fenofibrate)、氯貝丁酯(clofibrate)、吉非羅齊(gemfibrozil)、依託貝特(etofibrate)及(etofyllinclofibrate)；菸鹼酸及其衍生物，諸如阿昔莫司(acipimox)；PPAR-α促效劑；PPAR-δ促效劑；醯基輔酶A：膽固醇醯基轉移酶(ACAT；EC2.3.1.26)抑制劑，諸如阿伐麥布(avasimibe)；膽固醇再吸收抑制劑，諸如依折麥布(ezetimib)；與膽汁酸結合之物質，諸如消膽胺(cholestyramine)、考來替潑(colestipol)及考來維侖(colesevelam)；膽汁酸轉移抑制劑；HDL調節活性物質，諸如D4F、逆向D4F、LXR調節活性物質及FXR調節活性物質；CETP抑制劑，諸如托徹普(torcetrapib)、JTT-705或來自WO 2007/005572之化合物12；LDL受體調節劑；及ApoB100反義RNA。一尤其較佳實例為約1mg至40mg或10mg至80mg一天一次劑量之阿托伐他汀。
降血壓之組合搭配物之實例為β-阻斷劑，諸如阿廷諾(atenolol)、比索洛爾(bisoprolol)、塞利洛爾(celiprolol)、美托洛爾(metoprolol)及卡維地洛(carvedilol)；利尿劑，諸如二氫氯噻嗪、氯噻酮 (chlortalidon)、氯磺水楊胺(xipamide)、呋喃苯胺酸(furosemide)、吡咯他尼(piretanide)、托拉塞米(torasemide)、螺內酯(spironolactone)、依普利酮(eplerenone)、胺氯吡嗪脒(amiloride)及胺苯喋啶(triamterene)；鈣通道阻斷劑，諸如胺氯地平(amlodipine)、硝苯吡啶(nifedipine)、尼群地平(nitrendipine)、尼索地平(nisoldipine)、尼卡地平(nicardipine)、非洛地平(felodipine)、拉西地平(lacidipine)、樂康比啶(lercanipidine)、馬尼地平(manidipine)、伊拉地平(isradipine)、尼伐地平(nilvadipine)、異搏定(verapamil)、加洛帕米(gallopamil)及硫氮酮(diltiazem)；ACE抑制劑，諸如雷米普利(ramipril)、賴諾普利(lisinopril)、西拉普利(cilazapril)、喹那普利(quinapril)、卡托普利(captopril)、依那普利(enalapril)、貝那普利(benazepril)、培哚普利(perindopril)、福辛普利(fosinopril)及群多普利(trandolapril)；以及血管緊張素II受體阻斷劑(ARB)，諸如替米沙坦(telmisartan)、坎地沙坦(candesartan)、纈沙坦(valsartan)、洛沙坦(losartan)、厄貝沙坦(irbesartan)、奧美沙坦(olmesartan)及依普羅沙坦(eprosartan)。尤其較佳之實例為每天50mg至200mg劑量之美托洛爾、每天2.5mg至10mg劑量之胺氯地平、每天2.5mg至15mg劑量之雷米普利、每天80mg至160mg劑量之纈沙坦及每天20mg至320mg或40mg至160mg劑量之替米沙坦。
增加血液中HDL含量之組合搭配物之實例為膽固醇酯轉移蛋白(CETP)抑制劑；內皮脂肪酶抑制劑；ABC1調節劑；LXRα拮抗劑；LXRβ促效劑；PPAR-δ促效劑；LXRα/β調節劑，及增加脂蛋白本體A-I之表現及/或血漿濃度之物質。
用於治療肥胖之組合搭配物之實例為諾美婷(sibutramine)；四氫利普司他汀(tetrahydrolipstatin)(奧利司他(orlistat))；艾利沙美(alizyme)；右芬氟拉明(dexfenfluramine)；阿索開(axokine)；大麻鹼 受體1拮抗劑，諸如CB1拮抗劑利蒙本特(rimonobant)；MCH-1受體拮抗劑；MC4受體促效劑；NPY5以及NPY2拮抗劑；β3-AR促效劑，諸如SB-418790及AD-9677；5HT2c受體促效劑，諸如APD 356；肌肉抑制素(myostatin)抑制劑；Acrp30及脂締素(adiponectin)；硬脂醯輔酶A脫飽和酶(SCD1)抑制劑；脂肪酸合成酶(FAS)抑制劑；CCK受體促效劑；胃內激素(Ghrelin)受體調節劑；Pyy3-36；阿來新(orexin)受體拮抗劑；及特索芬辛(tesofensine)。
用於治療動脈粥樣硬化之組合搭配物之實例為磷脂酶A2抑制劑；酪胺酸-激酶之抑制劑(50mg至600mg)，諸如PDGF-受體-激酶(參看EP-A-564409、WO 98/35958、US 5093330、WO 2004/005281及WO 2006/041976)；oxLDL抗體及oxLDL疫苗；apoA-1 Milano；ASA；及VCAM-1抑制劑。
用於治療心臟衰竭之組合搭配物之實例為β-阻斷劑，諸如阿廷諾、比索洛爾、塞利洛爾及美托洛爾；利尿劑，諸如二氫氯噻嗪、氯噻酮、氯磺水楊胺、呋喃苯胺酸、吡咯他尼、托拉塞米、螺內酯、依普利酮、胺氯吡嗪脒及胺苯喋啶；ACE抑制劑，諸如雷米普利、賴諾普利、西拉普利、喹那普利、卡托普利、依那普利、貝那普利、培哚普利、福辛普利及群多普利；以及血管緊張素II受體阻斷劑(ARB)，諸如替米沙坦、坎地沙坦、纈沙坦、洛沙坦、厄貝沙坦、奧美沙坦及依普羅沙坦；心糖苷，諸如地高辛(digoxin)及毛地黃毒苷(digitoxin)；組合α/β-阻斷劑，諸如卡維地洛(carvedilol)；B-型利尿鈉肽(BNP)及BNP-衍生之肽及BNP-融合產物。尤其較佳之實例為每天50mg至200mg劑量之美托洛爾、每天2.5mg至15mg劑量之雷米普利、每天80mg至160mg劑量之纈沙坦、每天20mg至320mg或40mg至160mg劑量之替米沙坦、25-100mg劑量之依普利酮、每天0.25mg至0.6mg劑量之地高辛、3.25mg至100mg劑量之卡維地洛、呈快速注 射形式2μg/kg隨後0.01μg/kg/min劑量之BNP(例如奈西立(nesiritide))。
包含選定DPP IV抑制劑之藥物組合含有例如1.75mg至10.5mg格列本脲、500mg至3000mg甲苯磺丁脲、0.5-6g格列美脲、2.5mg至40mg格列吡嗪、1-4×30mg格列喹酮、至3×25mg格列波脲、80mg至160mg格列齊特；500mg至1000mg，較佳500mg、850mg或1000mg二甲雙胍；60mg至180mg那格列奈；0.25mg至4mg瑞格列奈；2mg至45mg噻唑烷二酮；200mg至600mg metaglidase；2.5mg至5mg PPAR γ/α調節劑；0.1mg至100mg α葡糖苷酶阻斷劑；1-250IU胰島素；15μg至120μg普蘭林肽；5mg至80mg士他汀(statin)；50mg至1000mg纖維酸酯；1000mg至3000mg菸鹼酸或衍生物；約250mg阿昔莫司(acipimox)；約10mg膽固醇再吸收抑制劑；0.5g至30g膽汁酸結合物質；10mg至600mg且較佳10mg至120mg CETP抑制劑；2.5mg至100mg β-阻斷劑；3mg至200mg利尿劑；2.5mg至500mg鈣通道阻斷劑；1mg至40mg ACE抑制劑；5mg至600mg血管緊張素II受體阻斷劑；10mg至15mg諾美婷；約120mg奧利司他；15mg至30mg右芬氟拉明；或5mg至20mg大麻鹼受體拮抗劑，25mg至100mg劑量之依普利酮；每天0.25mg至0.6mg劑量之地高辛；3.25mg至100mg劑量之卡維地洛；呈快速注射形式2μg/kg隨後0.01μg/kg/min劑量之BNP(例如奈西立)。
實例
實例1：糖尿病前期之治療
本發明之DPPIV抑制劑對治療特徵為病理性空腹葡萄糖及/或葡 萄糖耐受性異常之糖尿病前期的功效可使用臨床研究來測試。在歷經較短時期(例如2-4週)之研究中，藉由在研究療法期結束後測定空腹葡萄糖值及/或餐後或負荷測試(口服葡萄糖耐受性測試或接受指定餐點後之食物耐受性測試)後之葡萄糖值且將其與開始研究之前的值比較及/或與安慰劑組之彼等值比較來檢驗治療之成功性。此外，果糖胺值可在療法前後測定且與初始值及/或安慰劑值相比較。空腹葡萄糖含量或非空腹葡萄糖含量顯著下降證明治療之功效。在歷經較長時期(12週或更長時間)之研究中，藉由測定HbA1c值，與初始值及/或與安慰劑組之值比較來測試治療之成功性。與初始值及/或安慰劑值相比，HbA1c值之顯著變化證明DPP IV抑制劑對治療糖尿病前期之功效。
實例2：預防顯性第二型糖尿病
治療患有病理性空腹葡萄糖及/或葡萄糖耐受性異常(糖尿病前期)之患者亦追求預防轉變成顯性第二型糖尿病之目標。治療之功效可在糖尿病前期患者經活性物質或活性物質之組合，或安慰劑或非藥物療法或其他藥劑治療較長時期(例如1-5年)之比較臨床研究中探查。在療法期間及在療法結束時，藉由測定空腹葡萄糖及/或負荷測試(例如，oGTT)來檢測多少患者出現顯性第二型糖尿病，亦即空腹葡萄糖含量>125mg/dl及/或根據oGTT之2h值>199mg/dl。與其他形式治療中之一者相比較，當以活性物質或活性物質之組合治療時，出現顯性第二型糖尿病之患者數目顯著減少時，即證明活性物質或活性物質之組合對預防糖尿病前期轉變為顯性糖尿病之功效。
實例3：第二型糖尿病之治療
用本發明之活性物質治療第二型糖尿病患者除產生葡萄糖代謝狀況短暫改善以外，從長遠上預防代謝狀況劣化。患者經本發明之活性物質或活性物質之組合治療較長時期，例如1-6年，且與已經其他 抗糖尿病藥劑治療之患者相比較可觀察到此結果。若未觀察到空腹葡萄糖及/或HbA1c值增加或僅觀察到其略有增加，則證明與經其他抗糖尿病藥劑治療之患者相比的治療成功。若與已經其他藥劑治療之患者相比，顯著較少百分比之經本發明之活性物質或本發明之活性物質之組合治療的患者在葡萄糖代謝位置處經受劣化(例如HbA1c值增加至>6.5%或>7%)達到指示用另外口服抗糖尿病藥劑或用胰島素或用胰島素類似物或用另一種抗糖尿病劑(例如GLP-1類似物)治療的程度，則進一步證明治療成功。
實例4：胰島素抗性之治療
在進行不同持續時間(例如2週至12個月)之臨床研究中，治療成功係使用高胰島素血症正常葡萄糖血症葡萄糖夾鉗研究來檢查。在研究結束時，與初始值相比或與安慰劑組或給定不同療法之組相比，葡萄糖輸注速率之顯著升高證明活性物質或活性物質之組合對治療胰島素抗性之功效。
實例5：糖尿病性高血脂或血脂異常之治療
在對第二型糖尿病患者進行不同持續時間(例如2週至60個月)之臨床研究中，治療成功係藉由測定總膽固醇、LDL-膽固醇、HDL-膽固醇及血漿甘油三酯來檢查。在研究期間或在研究結束時，與初始值相比或與安慰劑組或給定不同療法之組相比，總膽固醇、LDL-膽固醇或血漿甘油三酯顯著下降及/或HDL-膽固醇含量升高證明活性物質或活性物質之組合對治療糖尿病性血脂異常或高脂質血症之功效。
實例6：高血糖症之治療
在進行不同持續時間(例如1天至24個月)之臨床研究中，高血糖症患者之治療成功係藉由測定空腹葡萄糖或非空腹葡萄糖(例如在餐後或在oGTT或確定餐之負荷測試之後)來檢查。在研究期間或在研究結束時，與初始值相比或與安慰劑組或給定不同療法之組相比，此等 葡萄糖值顯著下降證明活性物質或活性物質之組合對治療高血糖症之功效。
實例7：妊娠性糖尿病之治療
在進行較短時期(例如2-4週)之臨床研究中，治療成功係藉由在研究之治療時期結束時測定空腹葡萄糖值及/或在餐後或在負荷測試(確定餐後之口服葡萄糖耐受性測試或食物耐受性測試)之後的葡萄糖值且將其與開始研究之前的值比較及/或與安慰劑組之值比較來檢查。此外，果糖胺值可在治療前後測定且與初始值及/或安慰劑值相比較。空腹葡萄糖含量或非空腹葡萄糖含量顯著下降證明活性物質或活性物質之組合之功效。
在進行較長時間之研究(12週或更長時間)中，治療成功係測定HbA1c值(與初始值及安慰劑組相比)來檢查。與起始值及/或安慰劑值相比，HbA1c值之顯著變化證明活性物質或活性物質之組合對治療妊娠性糖尿病之功效。
實例8：已患有妊娠性糖尿病之女性之治療
妊娠性糖尿病患者在懷孕之後感染顯性第二型糖尿病之風險顯著增加。療法可具有預防向顯性第二型轉變之目標。為達成此目的，有妊娠性糖尿病史之女性經本發明之活性物質或本發明之活性物質之組合或經安慰劑或經非藥物療法或經其他藥劑治療較長時期(例如1-4年)。在治療期間及在治療結束時，藉由測定空腹葡萄糖及/或藉由負荷測試(例如，oGTT)來進行檢查以確定多少患者已發展顯性第二型糖尿病(空腹葡萄糖含量>125mg/dl及/或oGTT後之2h值>199mg/dl)。與不同類型之療法相比，當以本發明之活性物質或本發明之活性物質之組合治療時，發展顯性第二型糖尿病之患者數目顯著減少證明活性物質或活性物質之組合對預防有妊娠性糖尿病史之女性之顯性糖尿病的功效。
實例9：微血管或大血管併發症之預防
用本發明之活性物質或本發明之活性物質之組合對第二型糖尿病或糖尿病前期患者的治療預防或減少微血管併發症(例如糖尿病性神經病、糖尿病性視網膜病、糖尿病性腎病、糖尿病足、糖尿病性潰瘍)或大血管併發症(例如心肌梗塞、急性冠狀動脈徵候群、不穩定型心絞痛、穩定型心絞痛、中風、周邊動脈阻塞性疾病、心肌病、心臟衰竭、心律異常、血管再狹窄)。第二型糖尿病或糖尿病前期患者經本發明之活性物質或本發明之活性物質之組合長期治療，例如歷時1-6年，且將其與已經其他抗糖尿病藥劑或經安慰劑治療之患者相比較。較少數目之單一併發症或多個併發症可證明與已經其他抗糖尿病藥劑或經安慰劑治療之患者相比的治療成功。在大血管事件、糖尿病足及/或糖尿病性潰瘍之情況下，藉由既往病歷及多種測試方法來計數。在糖尿病性視網膜病之情況下，治療成功係藉由電腦控制照明及評估眼睛背景或其他眼科方法來測定。在糖尿病性神經病之情況下，除既往病歷及臨床檢查以外，神經傳導率可例如使用校準音叉來量測。對於糖尿病性腎病，可在研究開始之前、在研究期間及在研究結束時探查以下參數：白蛋白之分泌、肌酸酐清除率、血清肌酸酐值、血清肌酸酐值倍增所歷經之時間、直至透析變成必需所歷經之時間。
實例10：代謝症候群之治療
本發明之活性物質或活性物質之組合之功效可在具有不同進行時間(例如12週至6年)之臨床研究中藉由測定空腹葡萄糖或非空腹葡萄糖(例如在餐後或在oGTT或確定餐之負荷測試之後)或HbA1c值來測試。在研究期間或在研究結束時，與初始值相比或與安慰劑組或給定不同療法之組相比，此等葡萄糖值或HbA1c值顯著下降證明活性物質或活性物質之組合對治療代謝症候群之功效。其實例為與在研究開始時之起始值相比或與經安慰劑或不同療法治療之患者組相比，收縮壓 及/或舒張壓降低、血漿甘油三酯下降、總膽固醇或LDL膽固醇減少、HDL膽固醇增加或體重減輕。
實例11：DPPIV抑制劑薄膜包衣錠劑
為製備粒化溶液，在周圍溫度下將共聚乙烯吡咯酮溶解於純水中。將DPP IV抑制劑、甘露糖醇、預膠化澱粉及玉米澱粉在合適之混合器中混合以製備預混物。將該預混物用粒化溶液潤濕且隨後在混合器中以高剪切速率粒化。將濕顆粒經由篩孔尺寸為1.6mm之篩進行篩檢。將該等顆粒在約60℃下在流化床乾燥器中乾燥直至獲得2-4%之乾燥失重值。壓製加工過之混合物以形成錠劑核心。
在合適之混合器中，在周圍溫度下將羥丙基甲基纖維素、聚乙二醇、滑石粉、二氧化鈦及氧化鐵懸浮於純水中以製備錠劑包衣用懸浮液。將錠劑核心用此懸浮液包衣直至獲得3%之重量增加。舉例而言，以下錠劑組合物可以此方式獲得：
實例12：增強蘭格罕氏島或β細胞之生命力及分泌能力
此實驗係在成功分離蘭格罕氏島或胰腺β細胞之後，藉由將其在含有1nmol/l至1μmol/l濃度，較佳1nmol/l及100nmol/l濃度之DPP IV抑制劑的介質中儲存、運輸或培養以供將來移植而進行。
此外，在蘭格罕氏島或胰腺β細胞移植之後，患者(且此等亦可為動物)經DPP IV抑制劑以介於1mg與200mg之間的日劑量，較佳以5mg及100mg劑量之DPP IV抑制劑治療以增強該等移植物之生命力及分泌能力。此藉由在用葡萄糖或增加胰島素分泌之另一種藥劑刺激之後分析胰島素分泌來測試。此外，品質改良亦可在活體外或動物模型中使用Diabetologia 42：566,1999或Diabetes 48：738 1999(investigation of apoptosis and inhibition thereof)中所述之TUNEL技術來檢查。
實例13：DPP IV抑制劑-二甲雙胍之組合治療
對於治療第二型糖尿病或糖尿病前期而言，本發明之DPP IV抑制劑可與抗糖尿病活性物質二甲雙胍以自由組合或固定組合形式組合於錠劑中。治療有效劑量之DPP IV抑制劑(例如介於0.1mg及100mg之間的劑量)可與不同劑量之二甲雙胍，例如與單次劑量為500mg、850mg或1000mg之二甲雙胍，總日劑量為500-2850mg之二甲雙胍，或與500mg、1000mg、1500mg或2000mg延遲釋放形式之二甲雙胍組合。與二甲雙胍之該組合之臨床功效可在臨床研究中進行測試。對此，第二型糖尿病或糖尿病前期患者經單獨DPP IV抑制劑或經單獨二甲雙胍或經DPP IV抑制劑與二甲雙胍之組合治療。治療持續介於2週與6年之間的時間。DPP-IV抑制劑與二甲雙胍之組合引起空腹葡萄糖及/或非空腹葡萄糖及/或HbA1c值與單獨DPP IV抑制劑或單獨二甲雙胍相比顯著更大程度減少可證明該組合適當且有效。
實例14：DPP IV抑制劑-格列酮(glitazone)之組合治療
對於治療第二型糖尿病或糖尿病前期而言，本發明之DPP IV抑制劑可與包含格列酮或噻唑烷二酮(例如吡格列酮或羅格列酮)之抗糖 尿病活性物質組以自由組合或固定組合形式組合於錠劑中。治療有效劑量之DPP IV抑制劑(例如介於0.1mg與100mg之間劑量)可與不同劑量之吡格列酮(15mg、30mg或45mg)或羅格列酮(2mg、4mg或8mg，一天給予一或兩次)組合。與羅格列酮或吡格列酮之該組合之臨床功效可在臨床研究中進行測試。對此，第二型糖尿病或糖尿病前期患者經單獨DPP IV抑制劑或經單獨羅格列酮或吡格列酮或經DPP IV抑制劑與羅格列酮或吡格列酮之組合治療。治療持續介於2週與6年之間的時間。DPP-IV抑制劑與羅格列酮或吡格列酮之組合引起空腹葡萄糖及/或非空腹葡萄糖及/或HbA1c值與單獨DPP IV抑制劑或單獨羅格列酮或吡格列酮相比顯著更大程度減少可證明該組合適當且有效。
實例15：DPP IV抑制劑-SGLT2抑制劑之組合治療
對於治療第二型糖尿病或糖尿病前期而言，本發明之DPP IV抑制劑可與包含SGLT-2抑制劑之抗糖尿病活性物質組以自由組合或固定組合形式組合於錠劑中。治療有效劑量之DPP IV抑制劑(例如介於0.1mg與100mg之間的劑量)可與不同劑量之SGLT-2抑制劑(0.5mg至1000mg)組合。與SGLT-2抑制劑之該組合之臨床功效可在臨床研究中進行測試。對此，第二型糖尿病或糖尿病前期患者經單獨DPP IV抑制劑或經單獨SGLT-2抑制劑或經DPP IV抑制劑與SGLT-2抑制劑之組合治療。治療持續介於2週與6年之間的時間。DPP-IV抑制劑與SGLT-2抑制劑之組合引起空腹葡萄糖及/或非空腹葡萄糖及/或HbA1c值與單獨DPP IV抑制劑或單獨SGLT-2抑制劑相比顯著更大程度減少可證明該組合適當且有效。
實例16：DPP IV抑制劑-抗高血壓劑之組合治療
對於治療第二型糖尿病或糖尿病前期或代謝症候群患者而言，本發明之DPP IV抑制劑可與抗高血壓活性物質以自由組合或固定組合形式組合於錠劑中。治療有效劑量之DPP IV抑制劑(例如介於0.1mg 與100mg之間的劑量)可與不同劑量之ACE-抑制劑(例如2.5mg至15mg雷米普利)、AT1-受體拮抗劑(例如20mg至160mg替米沙坦)、β-阻斷劑(例如50mg至200mg美托洛爾)或利尿劑(例如12.5mg至25mg二氫氯噻嗪)組合。與抗高血壓劑之該組合之臨床功效可在臨床研究中進行測試。對此，第二型糖尿病或糖尿病前期或代謝症候群患者經單獨DPP IV抑制劑或經單獨抗高血壓劑或經DPP IV抑制劑與抗高血壓劑之組合治療。治療持續介於2週與6年之間的時間。DPP-IV抑制劑與抗高血壓劑之組合降低空腹葡萄糖及/或非空腹葡萄糖及/或HbA1c值之程度至少與單獨DPP IV抑制劑差不多，且若DPP-IV抑制劑與抗高血壓劑之組合降低收縮壓及/或舒張壓之程度至少與單獨抗高血壓劑差不多，則可證明該組合適當且有效。
實例17：DPP IV抑制劑-降脂劑之組合治療
對於治療第二型糖尿病或糖尿病前期或代謝症候群或糖尿病性血脂異常或高脂質血症患者而言，本發明之DPP IV抑制劑可與降脂劑/HDL-升高劑以自由組合或固定組合形式組合於錠劑中。治療有效劑量之DPP IV抑制劑(例如介於0.1mg與100mg之間的劑量)可與不同劑量之士他汀(例如10mg至80mg阿托伐他汀或10mg至80mg辛伐他汀)、纖維酸酯(例如非諾貝特)、膽固醇吸收抑制劑或與諸如CETP-抑制劑(例如托徹普10mg至120mg一天一次或120mg每天兩次)之HDL-升高物質組合。與降脂劑/HDL-升高劑之該組合之臨床功效可在臨床研究中進行測試。對此，第二型糖尿病或糖尿病前期或代謝症候群或糖尿病性血脂異常或高脂質血症患者經單獨DPP IV抑制劑或經單獨降脂劑/HDL-升高劑或經DPP IV抑制劑與降脂劑/HDL-升高劑之組合治療。治療持續介於2週與6年之間的時間。DPP-IV抑制劑與降脂劑/HDL-升高劑之組合降低空腹葡萄糖及/或非空腹葡萄糖及/或HbA1c值之程度至少與單獨DPP IV抑制劑差不多，且若DPP-IV抑制劑與降脂 劑/HDL-升高劑之組合降低總膽固醇或LDL-膽固醇或血漿甘油三酯之程度或增加HDL-膽固醇值之程度至少與單獨降脂劑/HDL-升高劑差不多，則可證明該組合適當且有效。
實例18：DPP IV抑制劑-BNP/NP衍生之肽或BNP-融合肽對心臟衰竭患者之組合治療
對於治療急性心臟衰竭患者而言，本發明DPP IV抑制劑可與有利影響心臟衰竭之物質以自由組合或固定組合形式組合於錠劑中。治療有效劑量之DPP IV抑制劑(例如介於0.1mg與100mg之間的劑量)可與不同劑量之ACE-抑制劑(例如2.5mg至15mg雷米普利)、AT1-受體拮抗劑(例如20mg至160mg替米沙坦)、β-阻斷劑(例如50mg至200mg美托洛爾)、組合α/β-阻斷劑(例如3.25mg至100mg卡維地洛)、利尿劑(例如12.5mg至25mg二氫氯噻嗪)、鹽皮質激素受體拮抗劑(例如25mg至100mg依普利酮；及/或B-型利尿鈉肽(BNP))(例如呈快速注射形式22μg/kg隨後0.01μg/kg/min奈西立)、BNP衍生之肽或BNP-融合產物組合。BNP與DPP-IV抑制劑之組合在活體內產生較高濃度之全長BNP(1-32)。指定組合之臨床功效可在臨床研究中進行測試。治療持續介於1天與6年之間的時間。與其他療法相比，該組合引起臨床狀況顯著改善(較高心臟射血輸出及/或肺充血逆轉、及/或肺楔壓逆轉、及/或由急性心臟衰竭引起之死亡率降低)可證明該組合有效治療急性心臟衰竭。
實例19：DPP-IV抑制劑治療心臟衰竭患者
本發明之DPP IV抑制劑可用以治療慢性心臟衰竭患者。此治療在活體內產生較高濃度之內源性全長BNP(1-32)。此治療之臨床功效可在臨床研究中進行測試。治療持續介於2週與6年之間的時間。與不同治療或安慰劑相比，本發明之DPP-IV抑制劑引起臨床狀況顯著改善(歸因於急性心臟衰竭之住院治療頻率較低、行走較長距離之能 力、較高測力學負荷能力、較高心臟射血輸出及/或肺充血逆轉、及/或由慢性心臟衰竭引起之死亡率降低)可證明該組合有效治療慢性心臟衰竭。

Claims (1)

  1. 一種式(I)之DPP IV抑制劑或其鹽中之一者之用途， 其特徵為R1表示(3-氰基-吡啶-2-基)甲基，且R2表示3-(R)-胺基-哌啶-1-基，其係用於製備供治療性處理已經確診患有選自糖尿病足及糖尿病相關潰瘍之生理功能性病症之患者之藥劑。
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Families Citing this family (120)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100926247B1 (ko) * 2001-02-24 2009-11-12 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 크산틴 유도체를 포함하는 약제학적 조성물 및 이의제조방법
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7569574B2 (en) 2002-08-22 2009-08-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Purine derivatives, the preparation thereof and their use as pharmaceutical compositions
US7495005B2 (en) * 2002-08-22 2009-02-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, their preparation and their use in pharmaceutical compositions
US7482337B2 (en) 2002-11-08 2009-01-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10254304A1 (de) * 2002-11-21 2004-06-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
US7566707B2 (en) * 2003-06-18 2009-07-28 Boehringer Ingelheim International Gmbh Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10355304A1 (de) 2003-11-27 2005-06-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
US7501426B2 (en) 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
DE102004009039A1 (de) * 2004-02-23 2005-09-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel
US7179809B2 (en) * 2004-04-10 2007-02-20 Boehringer Ingelheim International Gmbh 2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
US7439370B2 (en) 2004-05-10 2008-10-21 Boehringer Ingelheim International Gmbh Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
DE102004030502A1 (de) * 2004-06-24 2006-01-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel
DE102004043944A1 (de) * 2004-09-11 2006-03-30 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 8-(3-Amino-piperidin-1-yl)-7-(but-2-inyl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
DE102004044221A1 (de) * 2004-09-14 2006-03-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 3-Methyl-7-butinyl-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
DE102004054054A1 (de) 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
UA91546C2 (uk) * 2005-05-03 2010-08-10 Бьорінгер Інгельхайм Інтернаціональ Гмбх КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ
US7772191B2 (en) 2005-05-10 2010-08-10 Boehringer Ingelheim International Gmbh Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein
DE102005035891A1 (de) 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
JP5345846B2 (ja) * 2005-09-08 2013-11-20 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング １−クロロ−４−（β−Ｄ−グルコピラノス−１−イル）−２−（４−エチニル−ベンジル）−ベンゼンの結晶形態、その製造方法及び薬剤製造のためのそれらの使用
UY30082A1 (es) 2006-01-11 2007-08-31 Boehringer Ingelheim Int Forma cristalina de 1-(1-metiletil)-4`-((2-fluoro-4-metoxifenil)metil)-5`- metil-1h-pirazol-3`-o-b-d-glucopiranosido, un metodo para su preparacion y el uso de la misma para preparar medicamentos
PE20080697A1 (es) 2006-05-03 2008-08-05 Boehringer Ingelheim Int Derivados de benzonitrilo sustituidos con glucopiranosilo, composiciones farmaceuticas que contienen compuestos de este tipo, su uso y procedimiento para su fabricacion
PE20080251A1 (es) 2006-05-04 2008-04-25 Boehringer Ingelheim Int Usos de inhibidores de dpp iv
EP1852108A1 (en) * 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
NO347644B1 (no) 2006-05-04 2024-02-12 Boehringer Ingelheim Int Polymorfer
US20080020987A1 (en) * 2006-07-20 2008-01-24 Waldemar Pfrengle Processes for preparing pyrazole-O-glycoside derivatives and novel intermediates of said processes
EP2057160A1 (en) 2006-08-08 2009-05-13 Boehringer Ingelheim International GmbH Pyrrolo [3, 2 -d]pyrimidines as dpp-iv inhibitors for the treatment of diabetes mellitus
CA2656847A1 (en) * 2006-08-15 2008-02-21 Boehringer Ingelheim International Gmbh Glucopyranosyl-substituted cyclopropylbenzene derivatives, pharmaceutical compositions containing such compounds, their use as sglt inhibitors and process for their manufacture
EP2086991A1 (en) * 2006-10-27 2009-08-12 Boehringer Ingelheim International GmbH CRYSTALLINE FORM OF 4-(ß-D-GLUCOPYRANOS-1-YL)-1-METHYL-2-[4-((S)-TETRAHYDROFURAN-3-YLOXY)-BENZYL]-BENZENE, A METHOD FOR ITS PREPARATION AND THE USE THEREOF FOR PREPARING MEDICAMENTS
UY31291A1 (es) * 2007-08-16 2009-03-31 Composicion farmacéutica que comprende un derivado de pirazol-0-glucosido
CL2008002427A1 (es) * 2007-08-16 2009-09-11 Boehringer Ingelheim Int Composicion farmaceutica que comprende 1-cloro-4-(b-d-glucopiranos-1-il)-2-[4-((s)-tetrahidrofurano-3-iloxi)bencil]-benceno combinado con 1-[(4-metilquinazolin-2-il)metil]-3-metil-7-(2-butin-1-il)-8-(3-(r)-aminopiperidin-1-il)xantina; y su uso para tratar diabetes mellitus tipo 2.
PE20090987A1 (es) * 2007-08-16 2009-08-14 Boehringer Ingelheim Int Composicion farmaceutica que comprende un derivado de pirazol-o-glucosido
PE20090603A1 (es) * 2007-08-16 2009-06-11 Boehringer Ingelheim Int Composicion farmaceutica que comprende un inhibidor de sglt2 y un inhibidor de dpp iv
CN101784278A (zh) 2007-08-17 2010-07-21 贝林格尔.英格海姆国际有限公司 用于治疗fab-相关的疾病的嘌呤衍生物
US8648085B2 (en) * 2007-11-30 2014-02-11 Boehringer Ingelheim International Gmbh 1, 5-dihydro-pyrazolo (3, 4-D) pyrimidin-4-one derivatives and their use as PDE9A mudulators for the treatment of CNS disorders
CL2008003653A1 (es) * 2008-01-17 2010-03-05 Mitsubishi Tanabe Pharma Corp Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica.
UA105362C2 (en) * 2008-04-02 2014-05-12 Бьорингер Ингельхайм Интернациональ Гмбх 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators
AR071175A1 (es) 2008-04-03 2010-06-02 Boehringer Ingelheim Int Composicion farmaceutica que comprende un inhibidor de la dipeptidil-peptidasa-4 (dpp4) y un farmaco acompanante
BRPI0916997A2 (pt) 2008-08-06 2020-12-15 Boehringer Ingelheim International Gmbh Inibidor de dpp-4 e seu uso
UY32030A (es) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
EA031225B1 (ru) 2008-08-15 2018-12-28 Бёрингер Ингельхайм Интернациональ Гмбх Ингибиторы дпп-4 для заживления ран
AP2011005672A0 (en) 2008-09-08 2011-04-30 Boehringer Ingelheim Int Pyrazolopyrimidines and their use for the treatment of CNS disorders.
AU2009290911A1 (en) 2008-09-10 2010-03-18 Boehringer Ingelheim International Gmbh Combination therapy for the treatment of diabetes and related conditions
US20200155558A1 (en) 2018-11-20 2020-05-21 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
CN102316889B (zh) 2008-11-26 2014-11-26 萨蒂奥根制药公司 组合物及使用方法
CA2745037C (en) 2008-12-23 2020-06-23 Boehringer Ingelheim International Gmbh Salt forms of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8(3-(r)-amino-piperidin-1-yl)-xanthine
AR074990A1 (es) 2009-01-07 2011-03-02 Boehringer Ingelheim Int Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina
AR075204A1 (es) 2009-01-29 2011-03-16 Boehringer Ingelheim Int Inhibidores de dpp-4 y composiciones farmaceuticas que los comprenden, utiles para tratar enfermedades metabolicas en pacientes pediatricos, particularmente diabetes mellitus tipo 2
NZ594024A (en) * 2009-02-13 2013-08-30 Boehringer Ingelheim Int Pharmaceutical composition comprising glucopyranosyl diphenylmethane derivatives, pharmaceutical dosage form thereof, process for their preparation and uses thereof for improved glycemic control in a patient
KR20160143897A (ko) * 2009-02-13 2016-12-14 베링거 인겔하임 인터내셔날 게엠베하 Ｄｐｐ－４ 억제제(리나글립틴)을 임의로 다른 당뇨병 치료제와 병용하여 포함하는 당뇨병 치료 약제
GEP20135962B (en) 2009-02-13 2013-11-11 Boehringer Ingelheim Int Pharmaceutical composition comprising sglt2 inhibitor, dpp-iv inhibitor, and optionally further antidiabetic agent; and usage thereof
UY32427A (es) * 2009-02-13 2010-09-30 Boheringer Ingelheim Internat Gmbh Composicion farmaceutica, forma farmaceutica, procedimiento para su preparacion, metodos de tratamiento y usos de la misma
BRPI1011533A2 (pt) * 2009-03-31 2016-03-29 Boehringer Ingelheim Int derivados de 1-heterocicil-1 5- diidro-pirazolo [3,4--d] pirimidin-4-ona e seu uso como moduladores de pde9a.
TW201118099A (en) * 2009-08-12 2011-06-01 Boehringer Ingelheim Int New compounds for the treatment of CNS disorders
WO2011039107A1 (en) 2009-09-30 2011-04-07 Boehringer Ingelheim International Gmbh Method for the preparation of a crystalline form of 1-chloro-4- (beta-d-glucopyranos-1-yl)-2-(4-((s)-tetrahydrofuran-3-yloxy)benzyl)benzene
PL2486029T3 (pl) 2009-09-30 2015-11-30 Boehringer Ingelheim Int Sposoby otrzymywania podstawionych glukopiranozylem pochodnych benzylo-benzenowych
UY32919A (es) * 2009-10-02 2011-04-29 Boehringer Ingelheim Int Composición farmacéutica, forma de dosificación farmacéutica, procedimiento para su preparación, mé todos para su tratamiento y sus usos
KR101763659B1 (ko) 2009-10-02 2017-08-01 베링거 인겔하임 인터내셔날 게엠베하 Ｂｉ―1356 및 메트포르민을 포함하는 약제학적 조성물
MX364651B (es) 2009-11-27 2019-05-03 Boehringer Ingelheim Int Gmbh Star Inhibidores de dpp-iv, tales como la linagliptina, y composiciones farmacéuticas o combinaciones que comprenden los mismos, para usarse en el tratamiento de pacientes diabéticos tipificados genéticamente.
TWI562775B (en) * 2010-03-02 2016-12-21 Lexicon Pharmaceuticals Inc Methods of using inhibitors of sodium-glucose cotransporters 1 and 2
CN102286011B (zh) * 2010-03-16 2017-10-03 美德（江西）生物科技有限公司 吡咯烷硼酸酯二肽基肽酶抑制剂及其药物组合物
JP2013522279A (ja) 2010-03-18 2013-06-13 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 糖尿病及び関連状態の治療で用いるｇｐｒ１１９作動薬とｄｄｐ−ｉｖ阻害薬リナグリプチンの組合せ
KR101927068B1 (ko) 2010-05-05 2018-12-10 베링거 인겔하임 인터내셔날 게엠베하 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법
JP5826830B2 (ja) 2010-05-05 2015-12-02 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ピオグリタゾンとリナグリプチンを含む医薬製剤
MX2012014247A (es) 2010-06-24 2013-01-18 Boehringer Ingelheim Int Terapia para la diabetes.
EP3053924A1 (en) 2010-08-12 2016-08-10 Boehringer Ingelheim International Gmbh 6-cycloalkyl-1, 5-dihydro-pyrazolo [3, 4-d]pyrimidin-4-one derivatives and their use as pde9a inhibitors
US9034883B2 (en) * 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
US8796338B2 (en) 2011-01-07 2014-08-05 Elcelyx Therapeutics, Inc Biguanide compositions and methods of treating metabolic disorders
US11759441B2 (en) 2011-01-07 2023-09-19 Anji Pharmaceuticals Inc. Biguanide compositions and methods of treating metabolic disorders
US9211263B2 (en) 2012-01-06 2015-12-15 Elcelyx Therapeutics, Inc. Compositions and methods of treating metabolic disorders
US9480663B2 (en) 2011-01-07 2016-11-01 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
JP2014501787A (ja) 2011-01-07 2014-01-23 エルセリクス セラピューティクス インコーポレイテッド 化学感覚受容体リガンドに基づく治療法
US9572784B2 (en) 2011-01-07 2017-02-21 Elcelyx Therapeutics, Inc. Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk
CN102617566B (zh) * 2011-01-30 2015-03-04 山东轩竹医药科技有限公司 吡啶并咪唑烷衍生物
US20130035281A1 (en) 2011-02-09 2013-02-07 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US8809345B2 (en) 2011-02-15 2014-08-19 Boehringer Ingelheim International Gmbh 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders
EP2680851B1 (en) * 2011-03-03 2016-08-17 Merck Sharp & Dohme Corp. Fused bicyclic heterocycles useful as dipeptidyl peptidase-iv inhibitors
UY33937A (es) 2011-03-07 2012-09-28 Boehringer Ingelheim Int Composiciones farmacéuticas que contienen inhibidores de dpp-4 y/o sglt-2 y metformina
WO2012170702A1 (en) 2011-06-08 2012-12-13 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
EA030121B1 (ru) 2011-07-15 2018-06-29 Бёрингер Ингельхайм Интернациональ Гмбх Замещенные хиназолины, их получение и их применение в фармацевтических композициях
CN102362866A (zh) * 2011-11-21 2012-02-29 郑飞雄 一种治疗糖尿病及肥胖症的药物组合物
US20130172244A1 (en) 2011-12-29 2013-07-04 Thomas Klein Subcutaneous therapeutic use of dpp-4 inhibitor
SG10201901922VA (en) * 2012-01-06 2019-04-29 Elcelyx Therapeutics Inc Compositions and methods for treating metabolic disorders
BR112014016808B1 (pt) 2012-01-06 2022-01-11 Anji Pharma (Us) Llc Uso de um composto de biguanida para a fabricação de um medicamento para baixar os níveis de glicose no sangue e para o tratamento de um distúrbio do metabolismo de glicose
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
CN104487070A (zh) * 2012-03-16 2015-04-01 格卢科克斯生物科技有限公司 显示nox4抑制活性的基于噻吩的化合物及其用于治疗的用途
US9192617B2 (en) 2012-03-20 2015-11-24 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
JP6218811B2 (ja) 2012-05-14 2017-10-25 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
JP6224084B2 (ja) 2012-05-14 2017-11-01 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
JP6374862B2 (ja) 2012-05-24 2018-08-15 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 自己免疫性糖尿病、特に、ｌａｄａの治療に使用するためのｄｐｐ−４阻害剤としてのキサンチン誘導体
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
WO2014045266A1 (en) 2012-09-24 2014-03-27 Ulf Eriksson Treatment of type 2 diabetes and related conditions
UA116217C2 (uk) 2012-10-09 2018-02-26 Санофі Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону
UA116553C2 (uk) 2012-12-21 2018-04-10 Санофі Пептидна сполука - агоніст рецептора glp-1 i glp
SI2978859T1 (sl) 2013-03-27 2018-10-30 F. Hoffmann-La Roche Ag Genetski označevalci za napovedovanje odzivnosti na terapijo
US11813275B2 (en) 2013-04-05 2023-11-14 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US20140303097A1 (en) 2013-04-05 2014-10-09 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
US20140303098A1 (en) 2013-04-05 2014-10-09 Boehringer Ingelheim International Gmbh Pharmaceutical composition, methods for treating and uses thereof
EP4000608A1 (en) 2013-04-18 2022-05-25 Boehringer Ingelheim International GmbH Pharmaceutical composition, methods for treating and uses thereof
WO2014184742A1 (en) 2013-05-13 2014-11-20 Ranbaxy Laboratories Limited Pharmaceutical compositions containing a biguanide and a low dose antidiabetic agent
US20140371243A1 (en) * 2013-06-14 2014-12-18 Boehringer Ingelheim International Gmbh Medical use of a dpp-4 inhibitor
TW201609796A (zh) 2013-12-13 2016-03-16 賽諾菲公司 非醯化之艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物
EP3080150B1 (en) 2013-12-13 2018-08-01 Sanofi Exendin-4 peptide analogues as dual glp-1/gip receptor agonists
TW201609797A (zh) 2013-12-13 2016-03-16 賽諾菲公司 雙重ｇｌｐ－１／升糖素受體促效劑
TW201609799A (zh) 2013-12-13 2016-03-16 賽諾菲公司 雙重ｇｌｐ－１／ｇｉｐ受體促效劑
WO2015128453A1 (en) 2014-02-28 2015-09-03 Boehringer Ingelheim International Gmbh Medical use of a dpp-4 inhibitor
TW201625670A (zh) 2014-04-07 2016-07-16 賽諾菲公司 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑
TW201625668A (zh) 2014-04-07 2016-07-16 賽諾菲公司 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物
TW201625669A (zh) 2014-04-07 2016-07-16 賽諾菲公司 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑
US9932381B2 (en) 2014-06-18 2018-04-03 Sanofi Exendin-4 derivatives as selective glucagon receptor agonists
KR102456013B1 (ko) 2014-07-30 2022-10-18 에프. 호프만-라 로슈 아게 고밀도 지질단백질(hdl)-상승 제제 또는 hdl-모방 제제에 의한 치료법에 대한 반응성을 예측하기 위한 유전 표지
AR105319A1 (es) 2015-06-05 2017-09-27 Sanofi Sa Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico
AR105284A1 (es) 2015-07-10 2017-09-20 Sanofi Sa Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón
US10813909B2 (en) * 2016-05-19 2020-10-27 The Regents Of The University Of California Triple drug combination (metformin, simvastatin, digoxin) for targeted treatment of pancreatic cancer
EP4233840A3 (en) 2016-06-10 2023-10-18 Boehringer Ingelheim International GmbH Combinations of linagliptin and metformin
EP3551202B1 (en) 2016-12-06 2024-01-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of enhancing the potency of incretin-based drugs in subjects in need thereof
WO2019228363A1 (zh) 2018-05-31 2019-12-05 华领医药技术（上海）有限公司 含有葡萄糖激酶激活剂和k-atp通道阻断剂的药物组合、组合物和复方制剂及其制备方法和用途
WO2020016230A1 (en) 2018-07-17 2020-01-23 Boehringer Ingelheim International Gmbh Cardio- and renosafe antidiabetic therapy
CA3103992A1 (en) 2018-07-17 2020-01-23 Boehringer Ingelheim International Gmbh Cardiosafe antidiabetic therapy
WO2021053076A1 (en) * 2019-09-17 2021-03-25 Novartis Ag Combination therapy with vildagliptin and metformin

Family Cites Families (785)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2056046A (en) 1933-05-19 1936-09-29 Rhone Poulenc Sa Manufacture of bases derived from benz-dioxane
US2375138A (en) 1942-05-01 1945-05-01 American Cyanamid Co Alkamine esters of aryloxymethyl benzoic acid
US2629736A (en) 1951-02-24 1953-02-24 Searle & Co Basically substituted n-alkyl derivatives of alpha, beta, beta-triarylpropionamides
US2730544A (en) 1952-07-23 1956-01-10 Sahyun Lab Alkylaminoalkyl esters of hydroxycyclohexylbenzoic acid
US2750387A (en) 1953-11-25 1956-06-12 Searle & Co Basically substituted derivatives of diarylaminobenzamides
DE1211359B (de) 1955-11-29 1966-02-24 Oreal Oxydationsmittelfreies Kaltfaerbemittel fuer menschliches Haar
US2928833A (en) 1959-03-03 1960-03-15 S E Massengill Company Theophylline derivatives
US3174901A (en) * 1963-01-31 1965-03-23 Jan Marcel Didier Aron Samuel Process for the oral treatment of diabetes
US3454635A (en) * 1965-07-27 1969-07-08 Hoechst Ag Benzenesulfonyl-ureas and process for their manufacture
US3673241A (en) 1968-04-04 1972-06-27 Ciba Geigy Corp Substituted benzaldehyde guanylhydrazones
ES385302A1 (es) 1970-10-22 1973-04-16 Miquel S A Lab Procedimiento para la obtencion de derivados trisubstitui- dos de etilendiamina.
DE2205815A1 (de) 1972-02-08 1973-08-16 Hoechst Ag Piperazinderivate und verfahren zu ihrer herstellung
JPS5512435B2 (zh) 1972-07-01 1980-04-02
US4005208A (en) 1975-05-16 1977-01-25 Smithkline Corporation N-Heterocyclic-9-xanthenylamines
US4061753A (en) 1976-02-06 1977-12-06 Interx Research Corporation Treating psoriasis with transient pro-drug forms of xanthine derivatives
AU508480B2 (en) 1977-04-13 1980-03-20 Asahi Kasei Kogyo Kabushiki Kaisha Microcrystalline cellulose excipient and pharmaceutical composition containing thesame
NO154918C (no) 1977-08-27 1987-01-14 Bayer Ag Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin.
DE2758025A1 (de) 1977-12-24 1979-07-12 Bayer Ag Neue derivate von 3,4,5-trihydroxypiperidin, verfahren zu ihrer herstellung und ihre verwendung
DE2904885A1 (de) 1979-02-09 1980-08-14 Rothenberger Gmbh Co Biegevorrichtung fuer metallrohre
DE2929596A1 (de) 1979-07-21 1981-02-05 Hoechst Ag Verfahren zur herstellung von oxoalkyl-xanthinen
GB2084580B (en) 1980-10-01 1984-07-04 Glaxo Group Ltd Aminoalkyl furan derivative
US4382091A (en) 1981-04-30 1983-05-03 Syntex (U.S.A.) Inc. Stabilization of 1-substituted imidazole derivatives in talc
FR2558162B1 (fr) 1984-01-17 1986-04-25 Adir Nouveaux derives de la xanthine, leurs procedes de preparation et les compositions pharmaceutiques les renfermant
FI79107C (fi) 1984-06-25 1989-11-10 Orion Yhtymae Oy Foerfarande foer framstaellning av stabil -form av prazosinhydroklorid.
JPS6130567A (ja) 1984-07-23 1986-02-12 Shiseido Co Ltd 尿素の安定化法
JPS61124383A (ja) 1984-11-16 1986-06-12 Unitika Ltd 固定化線維素溶解活性酵素の安定化法
AR240698A1 (es) * 1985-01-19 1990-09-28 Takeda Chemical Industries Ltd Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales
CA1242699A (en) 1985-02-01 1988-10-04 Bristol-Myers Company Cefbuperazone and derivatives thereof
US4741898A (en) 1985-04-01 1988-05-03 Fisher Scientific Company Stabilized stain composition
US5258380A (en) 1985-06-24 1993-11-02 Janssen Pharmaceutica N.V. (4-piperidinylmethyl and -hetero)purines
GB8515934D0 (en) 1985-06-24 1985-07-24 Janssen Pharmaceutica Nv (4-piperidinomethyl and-hetero)purines
EP0223403B1 (en) 1985-10-25 1993-08-04 Beecham Group Plc Piperidine derivative, its preparation, and its use as medicament
US5034225A (en) 1985-12-17 1991-07-23 Genentech Inc. Stabilized human tissue plasminogen activator compositions
US5433959A (en) 1986-02-13 1995-07-18 Takeda Chemical Industries, Ltd. Stabilized pharmaceutical composition
ATE72244T1 (de) 1986-03-21 1992-02-15 Heumann Pharma Gmbh & Co Kristalline, wasserfreie sigma -form von 2-(4-(2furoyl-(2-piperazin)-1-yl>-4-amino-6,7- dimethoxychinazolinhydrochlorid und verfahren zu ihrer herstellung.
EP1498425A1 (en) 1986-05-05 2005-01-19 The General Hospital Corporation Use of glucagone-like-peptide 1 (GLP-1) derivatives for the preparation of pharmaceutical compositions
US5120712A (en) 1986-05-05 1992-06-09 The General Hospital Corporation Insulinotropic hormone
AU619444B2 (en) 1986-06-02 1992-01-30 Nippon Chemiphar Co. Ltd. 2-(2-aminobenzylsulfinyl)- benzimidazole derivatives
US4968672A (en) 1987-01-02 1990-11-06 The United States Of America As Represented By The Department Of Health And Human Services Adenosine receptor prodrugs
US4743450A (en) 1987-02-24 1988-05-10 Warner-Lambert Company Stabilized compositions
US5093330A (en) 1987-06-15 1992-03-03 Ciba-Geigy Corporation Staurosporine derivatives substituted at methylamino nitrogen
JPS6440433A (en) 1987-08-05 1989-02-10 Green Cross Corp Aqueous liquid composition of thrombin
CA1340285C (en) 1988-05-19 1998-12-22 Hiroyuki Nagano Novel quinolonecarboxylic acid derivatives having at 7-position a piperidin-1-yl substituent
US5329025A (en) 1988-09-21 1994-07-12 G. D. Searle & Co. 3-azido compound
US5234897A (en) 1989-03-15 1993-08-10 Bayer Aktiengesellschaft Herbicidal 3-amino-5-aminocarbonyl-1,2,4-triazoles
DE3926119A1 (de) 1989-08-08 1991-02-14 Bayer Ag 3-amino-5-aminocarbonyl-1,2,4-triazol-derivate
GB8906792D0 (en) 1989-03-23 1989-05-10 Beecham Wuelfing Gmbh & Co Kg Treatment and compounds
DE3916430A1 (de) 1989-05-20 1990-11-22 Bayer Ag Verfahren zur herstellung von 3-amino-5-aminocarbonyl-1,2,4-triazol-derivaten
US5332744A (en) 1989-05-30 1994-07-26 Merck & Co., Inc. Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists
IL94390A (en) 1989-05-30 1996-03-31 Merck & Co Inc The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them
US5223499A (en) 1989-05-30 1993-06-29 Merck & Co., Inc. 6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
HU208115B (en) 1989-10-03 1993-08-30 Biochemie Gmbh New process for producting pleuromutilin derivatives
FR2654935B1 (fr) 1989-11-28 1994-07-01 Lvmh Rech Utilisation de xanthines, eventuellement incorporees dans des liposomes, pour favoriser la pigmentation de la peau ou des cheveux.
CN1020944C (zh) 1990-01-30 1993-05-26 阿图尔-费希尔股份公司费希尔厂 紧固件
EP0443983B1 (de) 1990-02-19 1996-02-28 Ciba-Geigy Ag Acylverbindungen
KR930000861B1 (ko) 1990-02-27 1993-02-08 한미약품공업 주식회사 오메프라졸 직장투여 조성물
ES2064887T3 (es) 1990-09-13 1995-02-01 Akzo Nobel Nv Composiciones quimicas solidas estabilizadas.
GB9020959D0 (en) 1990-09-26 1990-11-07 Beecham Group Plc Novel compounds
US5084460A (en) 1990-12-24 1992-01-28 A. H. Robins Company, Incorporated Methods of therapeutic treatment with N-(3-ouinuclidinyl)-2-hydroxybenzamides and thiobenzamides
US5614519A (en) 1991-02-06 1997-03-25 Karl Thomae Gmbh (1-(2,3 or 4-N-morpholinoalkyl)-imidazol-4-yl)-benizimidazol-1-yl-methyl]-biphenyls useful as angiotensin-II antagonists
US5602127A (en) 1991-02-06 1997-02-11 Karl Thomae Gmbh (Alkanesultam-1-yl)-benzimidazol-1-yl)-1yl)-methyl-biphenyls useful as angiotensin-II antagonists
US5594003A (en) 1991-02-06 1997-01-14 Dr. Karl Thomae Gmbh Tetrahydroimidazo[1,2-a]pyridin-2-yl-(benzimidazol-1-yl)-methyl-biphenyls useful as angiotensin-II antagonists
GB9109862D0 (en) 1991-05-08 1991-07-03 Beecham Lab Sa Pharmaceutical formulations
DE4124150A1 (de) 1991-07-20 1993-01-21 Bayer Ag Substituierte triazole
TW225528B (zh) 1992-04-03 1994-06-21 Ciba Geigy Ag
US5300298A (en) 1992-05-06 1994-04-05 The Pennsylvania Research Corporation Methods of treating obesity with purine related compounds
GB9215633D0 (en) 1992-07-23 1992-09-09 Smithkline Beecham Plc Novel treatment
TW307769B (zh) 1992-07-31 1997-06-11 Shionogi & Co
TW252044B (zh) 1992-08-10 1995-07-21 Boehringer Ingelheim Kg
US5358941A (en) 1992-12-02 1994-10-25 Merck & Co., Inc. Dry mix formulation for bisphosphonic acids with lactose
DE4242459A1 (de) 1992-12-16 1994-06-23 Merck Patent Gmbh Imidazopyridine
AU6087894A (en) 1993-01-14 1994-08-15 Cell Therapeutics, Inc. Acetal or ketal substituted therapeutic compounds
EP0638567A4 (en) 1993-02-18 1995-05-10 Kyowa Hakko Kogyo Kk ADENOSINE INHIBITORS.
JP3726291B2 (ja) 1993-07-05 2005-12-14 三菱ウェルファーマ株式会社 安定な結晶構造を有するベンゾオキサジン化合物およびその製造法
FR2707641B1 (fr) 1993-07-16 1995-08-25 Fournier Ind & Sante Composés de l'imidazol-5-carboxamide, leur procédé de préparation leurs intermédiaires et leur utilisation en thérapeutique.
DE4339868A1 (de) 1993-11-23 1995-05-24 Merck Patent Gmbh Imidazopyridazine
DE4404183A1 (de) 1994-02-10 1995-08-17 Merck Patent Gmbh 4-Amino-1-piperidylbenzoylguanidine
US5545745A (en) 1994-05-23 1996-08-13 Sepracor, Inc. Enantioselective preparation of optically pure albuterol
CO4410190A1 (es) 1994-09-19 1997-01-09 Lilly Co Eli 3-[4-(2-AMINOETOXI)-BENZOIL]-2-ARIL-6-HIDROXIBENZO [b] TIOFENO CRISTALINO
EP0785927B1 (en) 1994-10-12 2003-08-27 Euroceltique S.A. Novel benzoxazoles
GB9501178D0 (en) 1995-01-20 1995-03-08 Wellcome Found Guanine derivative
WO1996036638A1 (en) 1995-05-19 1996-11-21 Chiroscience Limited Xanthines and their therapeutic use
EP0832065B1 (en) 1995-06-06 2001-10-10 Pfizer Inc. Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as glycogen phosphorylase inhibitors
EP0832066B1 (en) 1995-06-06 2001-09-12 Pfizer Inc. Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors
JPH08333339A (ja) 1995-06-08 1996-12-17 Fujisawa Pharmaceut Co Ltd 光学活性なピペリジン酢酸誘導体の製造法
GB9523752D0 (en) 1995-11-21 1996-01-24 Pfizer Ltd Pharmaceutical formulations
DE19543478A1 (de) 1995-11-22 1997-05-28 Bayer Ag Kristallines Hydrochlorid von {(R)-(-)-2- N-[4-(1,1-Dioxido-3-oxo-2,3-dihydrobenzisothiazol-2-yl)-buytl]-aminomethyl}-chroman
FR2742751B1 (fr) 1995-12-22 1998-01-30 Rhone Poulenc Rorer Sa Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent
WO1997023447A1 (en) 1995-12-26 1997-07-03 Alteon Inc. N-acylaminoalkylhydrazinecarboximidamides
US5891855A (en) 1996-02-12 1999-04-06 The Scripps Research Institute Inhibitors of leaderless protein export
DE122010000020I1 (de) 1996-04-25 2010-07-08 Prosidion Ltd Verfahren zur Senkung des Blutglukosespiegels in Säugern
TWI240627B (en) 1996-04-26 2005-10-01 Chugai Pharmaceutical Co Ltd Erythropoietin solution preparation
US5965555A (en) 1996-06-07 1999-10-12 Hoechst Aktiengesellschaft Xanthine compounds having terminally animated alkynol side chains
WO1997046526A1 (en) 1996-06-07 1997-12-11 Eisai Co., Ltd. Stable polymorphs of donepezil (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine) hydrochloride and process for production
US5958951A (en) 1996-06-14 1999-09-28 Novo Nordiskials Modified form of the R(-)-N-(4,4-di(3-methylthien-2-yl)but-3-enyl)-nipecotic acid hydrochloride
US5753635A (en) 1996-08-16 1998-05-19 Berlex Laboratories, Inc. Purine derivatives and their use as anti-coagulants
KR100516088B1 (ko) 1996-09-23 2005-09-22 일라이 릴리 앤드 캄파니 올란자핀 이수화물 ｄ
EP0937056A1 (en) 1996-10-28 1999-08-25 Novo Nordisk A/S A process for the preparation of (-)-3,4-trans-diarylchromans
UA65549C2 (uk) 1996-11-05 2004-04-15 Елі Ліллі Енд Компані Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція
ATE289517T1 (de) 1996-11-12 2005-03-15 Novo Nordisk As Verwendung von glp-1 peptiden
GB9623859D0 (en) 1996-11-15 1997-01-08 Chiroscience Ltd Novel compounds
CN1733296B (zh) 1996-12-24 2010-05-26 拜奥根Idec马萨诸塞公司 稳定的液体干扰素制剂
DE19705233A1 (de) 1997-02-12 1998-08-13 Froelich Juergen C Verfahren zur Herstellung einer Formulierung enthaltend Arginin
CO4950519A1 (es) 1997-02-13 2000-09-01 Novartis Ag Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion
US6011049A (en) 1997-02-19 2000-01-04 Warner-Lambert Company Combinations for diabetes
BR9808581A (pt) 1997-03-13 2000-05-30 Hexal Ag Estabilização de benzimidazóis sensìveis a ácido com combinações de aminoácido/ciclodextrina
US5972332A (en) 1997-04-16 1999-10-26 The Regents Of The University Of Michigan Wound treatment with keratinocytes on a solid support enclosed in a porous material
AR012894A1 (es) 1997-06-13 2000-11-22 Lilly Co Eli Formulacion de insulina en solucion estable, su uso para preparar un medicamento y proceso para la preparacion de la misma.
US6174548B1 (en) 1998-08-28 2001-01-16 Andrx Pharmaceuticals, Inc. Omeprazole formulation
PL340836A1 (en) 1997-12-05 2001-02-26 Astrazeneca Uk Ltd Novel compounds
TW589174B (en) 1997-12-10 2004-06-01 Takeda Chemical Industries Ltd Agent for treating high-risk impaired glucose tolerance
JPH11193270A (ja) 1997-12-26 1999-07-21 Koei Chem Co Ltd 光学活性１−メチル−３−ピペリジンメタノールの製造方法
DE69815554T2 (de) 1998-01-05 2004-05-06 Eisai Co., Ltd. Purinderivate und antagonisten des adenosin-a2-rezeptors, welche zur vorsorge oder heilung von diabetes dienen
CA2319195A1 (en) 1998-02-02 1999-08-05 Trustees Of Tufts College Method of regulating glucose metabolism, and reagents related thereto
US5998463A (en) 1998-02-27 1999-12-07 Pfizer Inc Glycogen phosphorylase inhibitors
US20030013740A1 (en) 1998-03-27 2003-01-16 Martin P. Redmon Stable dosage forms of fluoxetine and its enantiomers
IL138521A0 (en) 1998-03-31 2001-10-31 Nissan Chemical Ind Ltd Pyridazinone hydrochloride compound and method for producing the same
EP0950658A1 (en) 1998-04-13 1999-10-20 Takeda Chemical Industries, Ltd. 2-Pipirazinone-1-acetic acid dihydrochloride derivative used to inhibit platelet aggregation
US6207207B1 (en) 1998-05-01 2001-03-27 Mars, Incorporated Coated confectionery having a crispy starch based center and method of preparation
DE19823831A1 (de) 1998-05-28 1999-12-02 Probiodrug Ges Fuer Arzneim Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen
DE19828114A1 (de) 1998-06-24 2000-01-27 Probiodrug Ges Fuer Arzneim Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV
DE19828113A1 (de) 1998-06-24 2000-01-05 Probiodrug Ges Fuer Arzneim Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV
WO2000003735A1 (fr) 1998-07-15 2000-01-27 Asahi Kasei Kogyo Kabushiki Kaisha Excipient
EP0978279A1 (en) 1998-08-07 2000-02-09 Pfizer Products Inc. Inhibitors of human glycogen phosphorylase
CO5150173A1 (es) 1998-12-10 2002-04-29 Novartis Ag Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv
IT1312018B1 (it) 1999-03-19 2002-04-04 Fassi Aldo Procedimento migliorato per la produzione di sali non igroscopicidella l(-)-carnitina.
KR100455635B1 (ko) 1999-03-29 2004-11-06 에프. 호프만-라 로슈 아게 글루코키나제 활성화제
WO2000066101A2 (en) 1999-04-30 2000-11-09 City Of Hope Method of inhibiting glycation product formation
US20040152659A1 (en) 1999-05-12 2004-08-05 Fujisawa Pharmaceutical Co. Ltd. Method for the treatment of parkinson's disease comprising administering an A1A2a receptor dual antagonist
AR023966A1 (es) 1999-05-12 2002-09-04 Fujisawa Pharmaceutical Co Una composicion farmaceutica para la prevencion y/o el tratamiento de la enfermedad de parkinson y los sintomas concomitantes de la misma, y el uso de unantagonista dual receptor de adenosina a1 a2a para preparar dicha composicion
AU5294100A (en) 1999-05-27 2000-12-18 University Of Virginia Patent Foundation Method and compositions for treating the inflammatory response
CN100448482C (zh) 1999-05-31 2009-01-07 三菱化学株式会社 Hgf冻干制剂
US6545002B1 (en) 1999-06-01 2003-04-08 University Of Virginia Patent Foundation Substituted 8-phenylxanthines useful as antagonists of A2B adenosine receptors
CA2393195C (en) 1999-06-01 2007-02-20 Elan Pharma International Limited Small-scale mill and method thereof
PT1731511E (pt) 1999-06-21 2015-11-13 Boehringer Ingelheim Pharma Heterociclos bicíclicos, medicamentos contendo estes compostos, a sua utilização e processos para a sua preparação
US6448323B1 (en) 1999-07-09 2002-09-10 Bpsi Holdings, Inc. Film coatings and film coating compositions based on polyvinyl alcohol
ES2166270B1 (es) 1999-07-27 2003-04-01 Almirall Prodesfarma Sa Derivados de 8-fenil-6,9-dihidro-(1,2,4,)triazolo(3,4-i)purin-5-ona.
BRPI0013667B8 (pt) 1999-08-31 2021-05-25 Kissei Pharmaceutical derivados de glucopiranosiloxipirazol, composições medicinais contendo os mesmos e seus intermediários na produção deles
JP2003510304A (ja) 1999-09-29 2003-03-18 ノボ ノルディスク アクティーゼルスカブ 新規芳香族化合物
ATE257480T1 (de) 1999-09-30 2004-01-15 Pfizer Prod Inc Bicyclische pyrrolylamide als glycogenphosphorylase-inhibitoren
EP1391460A1 (en) 1999-09-30 2004-02-25 Pfizer Products Inc. Tricyclic pyrrolyl amides as glycogen phosphorylase inhibitors
PH12000002657B1 (en) 1999-10-12 2006-02-21 Bristol Myers Squibb Co C-aryl glucoside SGLT2 inhibitors
US6515117B2 (en) 1999-10-12 2003-02-04 Bristol-Myers Squibb Company C-aryl glucoside SGLT2 inhibitors and method
US6586438B2 (en) 1999-11-03 2003-07-01 Bristol-Myers Squibb Co. Antidiabetic formulation and method
GB9928330D0 (en) 1999-11-30 2000-01-26 Ferring Bv Novel antidiabetic agents
US6353111B1 (en) 1999-12-15 2002-03-05 Hoffmann-La Roche Inc. Trans olefinic glucokinase activators
HUP0600522A2 (en) 1999-12-23 2006-11-28 Novartis Ag Use of hypoglycemic agent for treating impaired glucose metabolism
WO2001051919A2 (en) 2000-01-07 2001-07-19 Transform Pharmaceuticals, Inc. High-throughput formation, identification, and analysis of diverse solid-forms
US6362172B2 (en) 2000-01-20 2002-03-26 Bristol-Myers Squibb Company Water soluble prodrugs of azole compounds
DK1248604T4 (da) 2000-01-21 2012-05-21 Novartis Ag Kombinationer indeholdende dipeptidylpeptidase-IV-inhibitorer og antidiabetiske midler
CO5271699A1 (es) 2000-01-24 2003-04-30 Pfizer Prod Inc Procedimiento para el tratamiento de cardiomiopatia utilizando inhibidores de la glucogeno fosforilasa
JP4621326B2 (ja) 2000-02-01 2011-01-26 エーザイ・アール・アンド・ディー・マネジメント株式会社 テプレノンの安定化組成物
AU782878B2 (en) 2000-02-05 2005-09-08 Vertex Pharmaceuticals Incorporated Pyrazole compositions useful as inhibitors of erk
WO2001062295A1 (fr) 2000-02-24 2001-08-30 Takeda Chemical Industries, Ltd. Medicaments contenant des ingredients actifs combines
EP1132389A1 (en) 2000-03-06 2001-09-12 Vernalis Research Limited New aza-indolyl derivatives for the treatment of obesity
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
GB0006133D0 (en) 2000-03-14 2000-05-03 Smithkline Beecham Plc Novel pharmaceutical
ES2254376T3 (es) 2000-03-17 2006-06-16 Kissei Pharmaceutical Co., Ltd. Derivados glucopiranosiloxibencilbenceno, preparaciones medicinales que los contienen e intermediarios para la preparacion de los indicados derivados.
EP1136071A3 (en) 2000-03-22 2003-03-26 Pfizer Products Inc. Use of glycogen phosphorylase inhibitors
JP2001278812A (ja) 2000-03-27 2001-10-10 Kyoto Pharmaceutical Industries Ltd 錠剤用崩壊剤及びこれを用いた錠剤
US6399101B1 (en) 2000-03-30 2002-06-04 Mova Pharmaceutical Corp. Stable thyroid hormone preparations and method of making same
US6683056B2 (en) 2000-03-30 2004-01-27 Bristol-Myers Squibb Company O-aryl glucoside SGLT2 inhibitors and method
US6555519B2 (en) 2000-03-30 2003-04-29 Bristol-Myers Squibb Company O-glucosylated benzamide SGLT2 inhibitors and method
AU4458401A (en) 2000-03-31 2001-10-15 Kirin Brewery Powdery preparation for transmucosal administration containing a polymeric form of drug and exhibiting improved storage stability
EP2266665B1 (en) 2000-03-31 2016-05-11 Royalty Pharma Collection Trust Method for the improvement of islet signaling in diabetes mellitus and for its prevention
JP2001292388A (ja) 2000-04-05 2001-10-19 Sharp Corp 再生装置
GB0008694D0 (en) 2000-04-07 2000-05-31 Novartis Ag Organic compounds
CN1209361C (zh) 2000-05-03 2005-07-06 霍夫曼-拉罗奇有限公司 含乙内酰脲的葡糖激酶激活剂
CA2407416C (en) 2000-05-03 2006-07-18 Paige Erin Mahaney Alkynyl phenyl heteroaromatic glucokinase activators
PT1283830E (pt) 2000-05-08 2008-08-18 Hoffmann La Roche Activadores da glucoquinase de fenilamida substituída com para-amino
JP3839723B2 (ja) 2000-05-08 2006-11-01 エフ．ホフマン−ラ ロシュ アーゲー 置換フェニルアセトアミドおよびグルコキナーゼ活性化剤としてのその使用
SE0001899D0 (sv) 2000-05-22 2000-05-22 Pharmacia & Upjohn Ab New compounds
JP4510372B2 (ja) 2000-06-09 2010-07-21 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング アシルフェニル尿素誘導体、その製造方法及び医薬としてのその使用
US6962998B2 (en) 2000-06-14 2005-11-08 Toray Industries, Inc. Processes for producing racemic piperidine derivative and for producing optically active piperidine derivative
US7078397B2 (en) 2000-06-19 2006-07-18 Smithkline Beecham Corporation Combinations of dipeptidyl peptidase IV inhibitors and other antidiabetic agents for the treatment of diabetes mellitus
GB0014969D0 (en) 2000-06-19 2000-08-09 Smithkline Beecham Plc Novel method of treatment
US6689353B1 (en) 2000-06-28 2004-02-10 Bayer Pharmaceuticals Corporation Stabilized interleukin 2
EP1301187B1 (en) 2000-07-04 2005-07-06 Novo Nordisk A/S Purine-2,6-diones which are inhibitors of the enzyme dipeptidyl peptidase iv (dpp-iv)
JP4138478B2 (ja) 2000-07-20 2008-08-27 エフ．ホフマン−ラ ロシュ アーゲー アルファ−アシル及びアルファ−ヘテロ原子置換ベンゼンアセトアミドのグルコキナーゼアクチベーター
NZ524618A (en) 2000-08-10 2004-08-27 Mitsubishi Pharma Corp Proline derivatives and use thereof as drugs
US6369232B1 (en) 2000-08-15 2002-04-09 Hoffmann-La Roche Inc. Tetrazolyl-phenyl acetamide glucokinase activators
GB0021831D0 (en) 2000-09-06 2000-10-18 Astrazeneca Ab Chemical compounds
US6821978B2 (en) 2000-09-19 2004-11-23 Schering Corporation Xanthine phosphodiesterase V inhibitors
DE60122193T2 (de) 2000-09-29 2007-07-05 Kissei Pharmaceutical Co., Ltd., Matsumoto Glucopyranosyloxybenzylbenzol derivate und medizinische zusammensetzungen, die diese verbindungen enthalten
WO2002036602A1 (fr) 2000-11-02 2002-05-10 Ajinomoto Co., Inc. Nouveaux derives du pyrazole et remedes au diabete contenant ces derniers
US20060034922A1 (en) 2000-11-03 2006-02-16 Andrx Labs, Llc Controlled release metformin compositions
US6722883B2 (en) 2000-11-13 2004-04-20 G & H Technologies Llc Protective coating for abrasive dental tools and burs
WO2002044192A1 (fr) 2000-11-30 2002-06-06 Kissei Pharmaceutical Co., Ltd. Derives de glucopyranosyloxybenzylbenzene, compositions medicinales contenant ces derives et produits intermediaires obtenus lors de l'elaboration de ces compositions
PT1341774E (pt) 2000-12-06 2006-05-31 Hoffmann La Roche Activadores heteroaromaticos, fundidos de glicocinase
US6821261B2 (en) 2000-12-12 2004-11-23 Dj Orthopedics, Llc Orthopedic brace having length-adjustable supports
US6482951B2 (en) 2000-12-13 2002-11-19 Hoffmann-La Roche Inc. Isoindolin-1-one glucokinase activators
WO2002051836A1 (fr) 2000-12-27 2002-07-04 Kyowa Hakko Kogyo Co., Ltd. Inhibiteur de dipeptidyl peptidase iv
MXPA03005923A (es) 2000-12-28 2004-01-26 Kissei Pharmaceuticals Co Ltd Derivados de glupopiranosiloxipirazol y su uso en medicinas.
FR2818906B1 (fr) 2000-12-29 2004-04-02 Dospharma Association medicamenteuse d'une biguanine et d'un transporteur, par exemple de metformine et d'arginine
FR2819254B1 (fr) 2001-01-08 2003-04-18 Fournier Lab Sa Nouveaux composes de la n-(phenylsulfonyl) glycine, leur procede de preparation et leur utilisation pour obtenir des compostions pharmaceutiques
DE10109021A1 (de) 2001-02-24 2002-09-05 Boehringer Ingelheim Pharma Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
DE10117803A1 (de) 2001-04-10 2002-10-24 Boehringer Ingelheim Pharma Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
DE60221098T2 (de) 2001-02-02 2008-01-24 Takeda Pharmaceutical Co. Ltd. Kondensierte heterocyclische derivate
TWI255817B (en) 2001-02-14 2006-06-01 Kissei Pharmaceutical Glucopyranosyloxybenzylbenzene derivatives and medicinal use thereof
US6649187B2 (en) 2001-02-16 2003-11-18 Bristol-Myers Squibb Pharma Company Use of polyalkylamine polymers in controlled release devices
US6610326B2 (en) 2001-02-16 2003-08-26 Andrx Corporation Divalproex sodium tablets
KR100926247B1 (ko) 2001-02-24 2009-11-12 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 크산틴 유도체를 포함하는 약제학적 조성물 및 이의제조방법
ES2319263T3 (es) 2001-02-26 2009-05-06 Kissei Pharmaceutical Co., Ltd. Derivados de glucopiranosilooxipirazol y su utilizacion como medicamentos.
ES2350084T3 (es) 2001-02-27 2011-01-18 Kissei Pharmaceutical Co., Ltd. Derivados de glucopiranosiloxipirazol y uso médico de los mismos.
US6936590B2 (en) 2001-03-13 2005-08-30 Bristol Myers Squibb Company C-aryl glucoside SGLT2 inhibitors and method
US6693094B2 (en) 2001-03-22 2004-02-17 Chrono Rx Llc Biguanide and sulfonylurea formulations for the prevention and treatment of insulin resistance and type 2 diabetes mellitus
GB0107383D0 (en) 2001-03-23 2001-05-16 Univ Edinburgh Lipid profile modulation
DE60209343T2 (de) 2001-04-11 2006-10-26 Bristol-Myers Squibb Co. Aminosäurekomplexe von c-arylglycosiden zur behandlung von diabetes und verfahren
WO2002088157A1 (fr) 2001-04-27 2002-11-07 Ajinomoto Co., Inc. Derives pyrazolyl-o-glycoside n-substitues et medicament contre le diabete en contenant
PE20021091A1 (es) 2001-05-25 2003-02-04 Aventis Pharma Gmbh Derivados de fenilurea sustituidos con carbonamida y procedimiento para su preparacion
JP2002348279A (ja) 2001-05-25 2002-12-04 Nippon Kayaku Co Ltd 光学活性ピリジルケトン誘導体の製造方法並びに光学活性ピリジルケトン誘導体
CA2448741C (en) 2001-05-30 2010-06-22 Kissei Pharmaceutical Co., Ltd. Glucopyranosyloxypyrazole derivative, medicinal composition containing the same, medicinal use thereof, and intermediate therefor
CN100376592C (zh) 2001-06-20 2008-03-26 橘生药品工业株式会社 含氮的杂环衍生物、含有该衍生物的药物组合物、其药物应用以及用于该衍生物制备的中间体
DE10130371A1 (de) 2001-06-23 2003-01-02 Boehringer Ingelheim Pharma Neue Arzneimittelkompositionen auf der Basis von Anticholinergika, Corticosteroiden und Betamimetika
US6901589B2 (en) * 2001-06-25 2005-05-31 Wind River Systems, Inc. System and method for determining a root cause of a failure
GB0115517D0 (en) 2001-06-25 2001-08-15 Ferring Bv Novel antidiabetic agents
SE0102299D0 (sv) 2001-06-26 2001-06-26 Astrazeneca Ab Compounds
SE0102300D0 (sv) 2001-06-26 2001-06-26 Astrazeneca Ab Compounds
ES2291477T3 (es) 2001-06-27 2008-03-01 Smithkline Beecham Corporation Fluoropirrolidinas como inhibidores de dipeptidil peptidasa.
CN1990468A (zh) 2001-06-27 2007-07-04 史密丝克莱恩比彻姆公司 作为二肽酶抑制剂的氟代吡咯烷
JP4115105B2 (ja) 2001-07-02 2008-07-09 協和醗酵工業株式会社 ピラゾール誘導体
JP2005502624A (ja) 2001-07-03 2005-01-27 ノボ　ノルディスク　アクティーゼルスカブ 糖尿病を治療するための、ｄｐｐ−ｉｖを阻害するプリン誘導体
US6869947B2 (en) 2001-07-03 2005-03-22 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme DPP-IV
UA74912C2 (en) 2001-07-06 2006-02-15 Merck & Co Inc Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes
WO2003006424A1 (en) 2001-07-10 2003-01-23 4Sc Ag Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents
WO2003011880A1 (fr) 2001-07-31 2003-02-13 Kissei Pharmaceutical Co., Ltd. Derive de glucopyranosyloxybenzylbenzene, composition medicinale contenant ce derive, usage medicinal de cette composition et produit intermediaire pour produire cette composition
US7638522B2 (en) 2001-08-13 2009-12-29 Janssen Pharmaceutica N.V. Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile
AR035119A1 (es) 2001-08-16 2004-04-14 Lilly Co Eli Anticuerpos humanos antagonistas anti-htnfsf13b
SE0102764D0 (sv) 2001-08-17 2001-08-17 Astrazeneca Ab Compounds
US20030087843A1 (en) 2001-09-05 2003-05-08 Washburn William N. O-pyrazole glucoside SGLT2 inhibitors and method of use
US20040259883A1 (en) 2001-09-14 2004-12-23 Hiroshi Sakashita Thiazolidine derivative and medicinal use thereof
AU2002331311A1 (en) 2001-09-19 2003-04-01 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme dpp-iv
US20050015820A1 (en) 2001-09-24 2005-01-20 Michael Cowley Assessment of neurons in the arcuate nucleus to screen for agents that modify feeding behavior
IL161335A0 (en) 2001-10-15 2004-09-27 Hemoteq Gmbh Coating of stents for preventing restenosis
DE10151296A1 (de) 2001-10-17 2003-04-30 Boehringer Ingelheim Pharma Keratinozyten verwendbar als biologisch aktive Substanz bei der Behandlung von Wunden
US6723340B2 (en) 2001-10-25 2004-04-20 Depomed, Inc. Optimal polymer mixtures for gastric retentive tablets
US6861440B2 (en) 2001-10-26 2005-03-01 Hoffmann-La Roche Inc. DPP IV inhibitors
US20030083354A1 (en) 2001-10-26 2003-05-01 Pediamed Pharmaceuticals, Inc. Phenylephrine tannate and pyrilamine tannate salts in pharmaceutical compositions
JPWO2003037864A1 (ja) 2001-10-29 2005-02-17 日本たばこ産業株式会社 インドール化合物及びその医薬用途
CN1604968A (zh) * 2001-10-31 2005-04-06 诺瓦提斯公司 基于tcf1基因多态性治疗糖尿病和相关病症的方法
CA2363053C (en) 2001-11-09 2011-01-25 Bernard Charles Sherman Clopidogrel bisulfate tablet formulation
WO2003044009A1 (en) 2001-11-22 2003-05-30 Biovitrum Ab Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
CA2466490C (en) 2001-11-22 2009-12-29 Biovitrum Ab Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
WO2003044000A1 (en) 2001-11-22 2003-05-30 Biovitrum Ab Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
CA2466870A1 (en) 2001-11-26 2003-06-05 Trustees Of Tufts College Methods for treating autoimmune disorders, and reagents related thereto
WO2003047626A1 (en) 2001-12-03 2003-06-12 Novo Nordisk A/S Use of a glucokinase activator in combination with a glucagon antagonist for treating type 2 diabetes
WO2003053929A1 (fr) 2001-12-21 2003-07-03 Toray Fine Chemicals Co., Ltd. Procede de production de derives de cis-piperidine optiquement actifs
EP1587574A4 (en) 2001-12-21 2009-03-18 Rhode Island Hospital 11b-HSD SELECTIVE INHIBITORS AND METHODS OF USE
HUP0402309A3 (en) 2001-12-21 2008-09-29 Novo Nordisk As Amide derivatives as glucokinase activators and pharmaceutical compositions containing them
US6727261B2 (en) 2001-12-27 2004-04-27 Hoffman-La Roche Inc. Pyrido[2,1-A]Isoquinoline derivatives
WO2003057245A1 (fr) 2001-12-28 2003-07-17 Nrl Pharma, Inc. Compositions servant a ameliorer le metabolisme lipidique
EP2329839B1 (en) 2002-01-10 2015-09-16 Imperial Innovations Limited Modification of feeding behavior by GLP-1 and PYY
US20070197552A1 (en) 2002-01-11 2007-08-23 Novo Nordisk A/S Method and composition for treatment of diabetes, hypertension, chronic heart failure and fluid retentive states
AU2003201274A1 (en) 2002-01-11 2003-07-24 Novo Nordisk A/S Compositions comprising inhibitors of dpp-iv and nep enzymes for the treatment of diabetes
MXPA04006997A (es) 2002-01-16 2004-12-07 Boehringer Ingelheim Pharma Comprimido farmaceutico de dos capas que comprende telmisartan y un diuretico y su preparacion.
CN1592749A (zh) 2002-01-18 2005-03-09 辉瑞产品公司 用于制备糖原磷酸化酶抑制剂的中间体
EP1477182A4 (en) 2002-01-21 2009-05-27 Nrl Pharma Inc NEW ANALGETICS
EP1333033A1 (en) 2002-01-30 2003-08-06 Boehringer Ingelheim Pharma GmbH & Co.KG FAP-activated anti-tumor compounds
CA2474168A1 (en) 2002-02-01 2003-08-14 Merck & Co., Inc. 11-beta-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia
WO2003063831A2 (en) 2002-02-01 2003-08-07 Pfizer Products Inc. Immediate release dosage forms containing solid drug dispersions
US7610153B2 (en) 2002-02-13 2009-10-27 Virginia Commonwealth University Multi-drug titration and evaluation
ES2627842T3 (es) 2002-02-21 2017-07-31 Valeant Pharmaceuticals Luxembourg S.À.R.L. Formas de dosificación de liberación controlada
EP1338595B1 (en) 2002-02-25 2006-05-03 Eisai Co., Ltd. Xanthine derivatives as DPP-IV inhibitors
MXPA03000966A (es) 2002-02-28 2003-09-04 Pfizer Prod Inc Agentes antidiabeticos.
GB0205162D0 (en) 2002-03-06 2002-04-17 Astrazeneca Ab Chemical compounds
GB0205170D0 (en) 2002-03-06 2002-04-17 Astrazeneca Ab Chemical compounds
HUP0200849A2 (hu) 2002-03-06 2004-08-30 Sanofi-Synthelabo N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra
GB0205176D0 (en) 2002-03-06 2002-04-17 Astrazeneca Ab Chemical compounds
GB0205175D0 (en) 2002-03-06 2002-04-17 Astrazeneca Ab Chemical compounds
GB0205165D0 (en) 2002-03-06 2002-04-17 Astrazeneca Ab Chemical compounds
GB0205166D0 (en) 2002-03-06 2002-04-17 Astrazeneca Ab Chemical compounds
WO2003080635A1 (fr) 2002-03-22 2003-10-02 Kissei Pharmaceutical Co., Ltd. Cristaux de derive de glucopyranosyloxybenzylbenzene
DE60328671D1 (de) 2002-03-26 2009-09-17 Banyu Pharma Co Ltd Neue aminobenzamidderivate
JP4298212B2 (ja) 2002-03-29 2009-07-15 大日本印刷株式会社 塩酸エピナスチン高融点型結晶の製造法
JP2003300977A (ja) 2002-04-10 2003-10-21 Sumitomo Pharmaceut Co Ltd キサンチン誘導体
DE10215907A1 (de) 2002-04-11 2003-11-06 Aventis Pharma Gmbh Acyl-4-carboxyphenyl-harnstoffderivate, Verfahren zu deren Herstellung und deren Verwendung
DE10215908B4 (de) 2002-04-11 2005-08-18 Aventis Pharma Deutschland Gmbh Acyl-3-carboxyphenyl-harnstoffderivate und deren Verwendung als Arzneimittel
US6683106B2 (en) 2002-04-15 2004-01-27 Pfizer Inc. N-(indole-2-carbonyl)-b-alaninamide crystal forms
AU2003226051A1 (en) 2002-04-16 2003-11-03 Banyu Pharmaceutical Co., Ltd. Solid forms of salts with tyrosine kinase activity
AU2003227360A1 (en) 2002-04-25 2003-11-10 Yamanouchi Pharmaceutical Co., Ltd. Novel amide derivatives or salts thereof
AU2003232204B8 (en) 2002-04-26 2009-07-30 F. Hoffmann-La Roche Ag Substituted phenylacetamides and their use as glucokinase activators
JP4424203B2 (ja) 2002-04-26 2010-03-03 味の素株式会社 糖尿病予防・治療剤
WO2003094909A2 (en) 2002-05-09 2003-11-20 Enos Pharmaceuticals, Inc. Methods and compositions for the treatment and prevention of intermittent claudication or alzheimer's disease
GB2388594A (en) * 2002-05-16 2003-11-19 Bayer Ag Imidazo-triazine PDE 4 inhibitors
US7057046B2 (en) 2002-05-20 2006-06-06 Bristol-Myers Squibb Company Lactam glycogen phosphorylase inhibitors and method of use
GB0212412D0 (en) 2002-05-29 2002-07-10 Novartis Ag Combination of organic compounds
JP2005529934A (ja) 2002-05-31 2005-10-06 シェーリング　コーポレイション キサンチンホスホジエステラーゼｖインヒビターおよびその前駆物質を調製するプロセス
AU2003241960B2 (en) 2002-06-06 2009-07-30 Eisai R&D Management Co., Ltd. Novel fused imidazole derivative
DE10225635C1 (de) 2002-06-07 2003-12-24 Aventis Pharma Gmbh N-Benzoylureido-Zimtsäurederivate, Verfahren zu deren Herstellung und deren Verwendung
ES2199061B1 (es) 2002-06-10 2005-02-16 Laboratorios Vita, S.A. Comprimidos bucodispersables y procedimiento para su obtencion.
AR040241A1 (es) 2002-06-10 2005-03-23 Merck & Co Inc Inhibidores de la 11-beta-hidroxiesteroide deshidrogrenasa 1 para el tratamiento de la diabetes obesidad y dislipidemia
FR2840897B1 (fr) 2002-06-14 2004-09-10 Fournier Lab Sa Nouveaux derives d'arylsulfonamides et leur utilisation en therapeutique
PL215132B1 (pl) 2002-06-27 2013-10-31 Novo Nordisk As Pochodna arylokarbonylowa jako srodek terapeutyczny, jej zastosowanie i kompozycja farmaceutyczna ja zawierajaca
US20040002615A1 (en) 2002-06-28 2004-01-01 Allen David Robert Preparation of chiral amino-nitriles
GB0215676D0 (en) 2002-07-05 2002-08-14 Novartis Ag Organic compounds
JP4374428B2 (ja) 2002-07-11 2009-12-02 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 尿素置換されたおよびウレタン置換されたアシル尿素、それらの製造方法および医薬としてのそれらの使用方法
NZ537603A (en) 2002-07-12 2006-09-29 Sanofi Aventis Deutschland Heterocyclically substituted benzoylureas, method for their production and their use as medicaments
US20040023981A1 (en) 2002-07-24 2004-02-05 Yu Ren Salt forms with tyrosine kinase activity
TW200409746A (en) 2002-07-26 2004-06-16 Theravance Inc Crystalline β2 adrenergic receptor agonist
JP2005533858A (ja) 2002-07-27 2005-11-10 アストラゼネカ アクチボラグ 化合物
TWI254635B (en) 2002-08-05 2006-05-11 Yamanouchi Pharma Co Ltd Azulene derivative and salt thereof
ATE469161T1 (de) 2002-08-08 2010-06-15 Kissei Pharmaceutical Pyrazolderivat, dieses enthaltende medizinische zusammensetzung, medizinische verwendung davon, und zwischenprodukt für dessen herstellung
WO2004014930A1 (ja) 2002-08-09 2004-02-19 Taisho Pharmaceutical Co., Ltd. 選択的なアリール５−チオ−β−Ｄ−アルドヘキソピラノシドの製造法
TW200404796A (en) 2002-08-19 2004-04-01 Ono Pharmaceutical Co Nitrogen-containing compound
EP2058311A3 (de) 2002-08-21 2011-04-13 Boehringer Ingelheim Pharma GmbH & Co. KG 8-[3-amino-piperidin-1-yl]-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
DE10238243A1 (de) 2002-08-21 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
US7569574B2 (en) 2002-08-22 2009-08-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Purine derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10238470A1 (de) 2002-08-22 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
US7495005B2 (en) 2002-08-22 2009-02-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, their preparation and their use in pharmaceutical compositions
DE10238477A1 (de) 2002-08-22 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Purinderivate, deren Herstellung und deren Verwendung als Arzneimittel
DE10238724A1 (de) 2002-08-23 2004-03-04 Bayer Ag Alkyl-substituierte Pyrazolpyrimidine
DE10238723A1 (de) 2002-08-23 2004-03-11 Bayer Ag Phenyl-substituierte Pyrazolyprimidine
JP2004137245A (ja) 2002-08-23 2004-05-13 Kissei Pharmaceut Co Ltd ピラゾール誘導体、それを含有する医薬組成物、その医薬用途及びその製造中間体
AU2003262262A1 (en) 2002-08-27 2004-03-19 Kissei Pharmaceutical Co., Ltd. Pyrazole derivatives, medicinal composition containing the same, and medicinal use thereof
AU2003262059A1 (en) 2002-09-11 2004-04-30 Takeda Pharmaceutical Company Limited Sustained release preparation
MXPA05002899A (es) 2002-09-16 2005-05-27 Wyeth Corp Formulaciones de liberacion controlada para administracion oral de un agente terapeutico polipeptido y sus metodos de uso.
US7262207B2 (en) 2002-09-19 2007-08-28 Abbott Laboratories Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
EP1557165A4 (en) 2002-09-26 2008-12-03 Eisai R&D Man Co Ltd COMBINED MEDICINE
BR0314864A (pt) 2002-10-03 2005-08-02 Novartis Ag Compostos orgânicos
DK1549638T3 (da) 2002-10-03 2008-01-21 Hoffmann La Roche Indol-3-carboxamider som glucokinase (GK) aktivatorer
DE10246434B4 (de) 2002-10-04 2005-08-04 Aventis Pharma Deutschland Gmbh Carboxyalkoxy-substituierte Acyl-carboxyphenyl-harnstoffderivate und ihre Verwendung als Arzneimittel
WO2004033455A2 (en) 2002-10-08 2004-04-22 Novo Nordisk A/S Hemisuccinate salts of heterocyclic dpp-iv inhibitors
US20060039968A1 (en) 2002-10-08 2006-02-23 Ramalingam Manikandan Gabapentin tablets and method for their preparation
US20040122048A1 (en) 2002-10-11 2004-06-24 Wyeth Holdings Corporation Stabilized pharmaceutical composition containing basic excipients
WO2004033427A1 (en) 2002-10-11 2004-04-22 Astrazeneca Ab 1,4-disubstituted piperidine derivatives and their use as 11-betahsd1 inhibitors
US6861526B2 (en) 2002-10-16 2005-03-01 Pfizer Inc. Process for the preparation of (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine
NZ538897A (en) 2002-10-18 2007-02-23 Merck & Co Inc Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
JP2004161749A (ja) 2002-10-24 2004-06-10 Toray Fine Chemicals Co Ltd 光学活性含窒素化合物の製造方法
KR20050059294A (ko) 2002-10-24 2005-06-17 스테릭스 리미티드 11-베타-하이드록시 스테로이드 데하이드로게나제 형태 1및 형태 2의 억제제
JP2006507359A (ja) 2002-10-28 2006-03-02 ノボ・ノルデイスク・エー／エス 心循環器疾患の治療のためのグリコーゲンホスホリラーゼ阻害剤の使用
WO2004048379A1 (ja) 2002-11-01 2004-06-10 Sumitomo Pharmaceuticals Co., Ltd. キサンチン化合物
AU2003276458A1 (en) 2002-11-07 2004-06-07 Astrazeneca Ab 2-oxo-ethanesulfonamide derivates
AU2003274462A1 (en) 2002-11-07 2004-06-07 Pfizer Products Inc. N-(indole-2-carbonyl) amides as anti-diabetic agents
MXPA05004890A (es) 2002-11-07 2005-07-22 Merck & Co Inc Derivados de fenilalanina como inhibidores de dipeptidilpeptidasa para el tratamiento o prevencion de diabetes.
DE10251927A1 (de) 2002-11-08 2004-05-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
US7482337B2 (en) 2002-11-08 2009-01-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10254304A1 (de) 2002-11-21 2004-06-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
US7109192B2 (en) * 2002-12-03 2006-09-19 Boehringer Ingelheim Pharma Gmbh & Co Kg Substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
UY28103A1 (es) 2002-12-03 2004-06-30 Boehringer Ingelheim Pharma Nuevas imidazo-piridinonas sustituidas, su preparación y su empleo como medicacmentos
JP4651934B2 (ja) 2002-12-04 2011-03-16 キッセイ薬品工業株式会社 ベンジルフェノール誘導体、それを含有する医薬組成物およびその医薬用途
DE60322944D1 (de) 2002-12-10 2008-09-25 Novartis Ag Kombinationen von einem dpp-iv inhibitor und einem ppar- alpha agonist
DE10258007B4 (de) 2002-12-12 2006-02-09 Sanofi-Aventis Deutschland Gmbh Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
DE10258008B4 (de) 2002-12-12 2006-02-02 Sanofi-Aventis Deutschland Gmbh Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
US7132425B2 (en) 2002-12-12 2006-11-07 Hoffmann-La Roche Inc. 5-substituted-six-membered heteroaromatic glucokinase activators
JP2004196702A (ja) 2002-12-18 2004-07-15 Yamanouchi Pharmaceut Co Ltd 新規なアミド誘導体又はその塩
DE10351663A1 (de) 2002-12-20 2004-07-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverförmige Arzneimittel enthaltend ein Tiotropiumsalz und Salmeterolxinafoat
JO2397B1 (en) 2002-12-20 2007-06-17 ميرك شارب اند دوم كوربوريشن Terazol derivatives as beta-hydroxy steroid dihydrogenase-1 inhibitors
US20040152720A1 (en) 2002-12-20 2004-08-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Powdered medicaments containing a tiotropium salt and salmeterol xinafoate
WO2004056744A1 (en) 2002-12-23 2004-07-08 Janssen Pharmaceutica N.V. Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors
CA2509835A1 (en) 2002-12-25 2004-07-15 Kissei Pharmaceutical Co., Ltd. Nitrogen-containing heterocyclic derivatives, medicinal compositions containing the same and medicinal use thereof
DE60336850D1 (en) 2003-01-06 2011-06-01 Lilly Co Eli Substituierte arylcyclopropylacetamide als glucokinaseaktivatoren
AU2003294376A1 (en) 2003-01-06 2004-08-10 Eli Lilly And Company Heteroaryl compounds
EP1599222B1 (en) 2003-01-08 2009-03-04 Novartis Vaccines and Diagnostics, Inc. Stabilized aqueous compositions comprising tissue factor pathway inhibitor (tfpi) or tissue factor pathway inhibitor variant
JP2006516572A (ja) 2003-01-14 2006-07-06 アリーナ ファーマシューティカルズ， インコーポレイテッド 代謝モジュレーターとしての１，２，３−トリ置換アリール誘導体および１，２，３−トリ置換ヘテロアリール誘導体ならびにこれらの誘導体に関連する糖尿病および高血糖のような障害の予防および処置
DE10335027A1 (de) * 2003-07-31 2005-02-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung von Angiotensin II Rezeptor Antagonisten
DE10302452B4 (de) 2003-01-23 2005-02-24 Aventis Pharma Deutschland Gmbh Carbonylamino-substituierte Acyl-phenyl-harnstoffderivate, Verfahren zu deren Herstellung und deren Verwendung
TW200503994A (en) 2003-01-24 2005-02-01 Novartis Ag Organic compounds
PL378117A1 (pl) 2003-02-11 2006-03-06 Prosidion Limited Tricyklopodstawione związki amidowe
WO2004072066A1 (en) 2003-02-11 2004-08-26 Prosidion Limited Tri(cyclo) substituted amide glucokinase activator compounds
AU2004220234C1 (en) 2003-02-13 2013-01-17 Msd K.K. Novel 2-pyridinecarboxamide derivatives
PE20040950A1 (es) 2003-02-14 2005-01-01 Theravance Inc DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS
DE10306502B4 (de) 2003-02-17 2005-03-17 Aventis Pharma Deutschland Gmbh Substituierte 3-(Benzoylureido)-thiophenderivate und sie enthaltende Arzneimittel
JP2004250336A (ja) 2003-02-18 2004-09-09 Kao Corp コーティング錠及び糖衣錠の製造法
AU2004215514B2 (en) 2003-02-26 2010-03-04 Msd K.K. Heteroarylcarbamoylbenzene derivative
US7135575B2 (en) 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
US7442387B2 (en) 2003-03-06 2008-10-28 Astellas Pharma Inc. Pharmaceutical composition for controlled release of active substances and manufacturing method thereof
DE10309929B4 (de) 2003-03-07 2006-02-23 Sanofi-Aventis Deutschland Gmbh Substituierte Benzoylureidopyridyl-piperidin- und -pyrrolidin-carbonsäurederivate, Verfahren zu deren Herstellung und deren Verwendung
EP1606290A1 (en) 2003-03-12 2005-12-21 Arizona Board of Regents, acting on behalf of the University of Arizona Weak base salts
PL1609785T3 (pl) 2003-03-14 2016-07-29 Astellas Pharma Inc Pochodne c-glikozydowe i ich sole
JP2006520335A (ja) 2003-03-18 2006-09-07 ノバルティス アクチエンゲゼルシャフト 脂肪酸とアミノ酸を含有する組成物
JP2004300102A (ja) 2003-03-31 2004-10-28 Kissei Pharmaceut Co Ltd 縮合複素環誘導体、それを含有する医薬組成物およびその医薬用途
EP1609799A4 (en) 2003-04-01 2008-10-29 Taisho Pharmaceutical Co Ltd HETEROARYL-5-THIO-BETA-D-GLUCOPYRANOSIDE DERIVATIVES AND AGENTS AGAINST DIABETES THEREOF
WO2004091623A1 (en) 2003-04-08 2004-10-28 Progenics Pharmaceuticals. Inc. Pharmaceutical formulations containing methylnaltrexone
WO2004089380A2 (en) 2003-04-11 2004-10-21 Novo Nordisk A/S Pharmaceutical use of fused 1,2,4-triazoles
JP4629657B2 (ja) 2003-04-11 2011-02-09 ハイ・ポイント・ファーマスーティカルズ、エルエルシー １１β−ヒドロキシステロイドデヒドロゲナーゼ１型化活性化合物
JP2006522745A (ja) 2003-04-11 2006-10-05 ノボ　ノルディスク　アクティーゼルスカブ 置換１，２，４−トリアゾールの薬学的使用
EP1615697A2 (en) 2003-04-11 2006-01-18 Novo Nordisk A/S New pyrazolo[1,5-a] pyrimidine derivatives and pharmaceutical use thereof
EP1620427A1 (en) 2003-04-17 2006-02-01 Pfizer Products Inc. Carboxamide derivatives as anti-diabetic agents
MXPA05011702A (es) 2003-04-30 2006-01-23 Pfizer Prod Inc Agentes antidiabeticos.
US20040220186A1 (en) 2003-04-30 2004-11-04 Pfizer Inc. PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease
JPWO2004096806A1 (ja) 2003-04-30 2006-07-13 大日本住友製薬株式会社 縮合イミダゾール誘導体
AU2003902263A0 (en) 2003-05-12 2003-05-29 Fujisawa Pharmaceutical Co., Ltd. Monosaccharide compounds
MXPA05012547A (es) 2003-05-21 2006-05-25 Prosidion Ltd Inhibidores de amida de acido pirrolopiridina-2-carboxilico de fosforilasa de glucogeno.
AU2004240885A1 (en) 2003-05-21 2004-12-02 Biovitrum Ab Inhibitors of 11-beta-hydroxy steroid dehydrogenase type I
TW200510277A (en) 2003-05-27 2005-03-16 Theravance Inc Crystalline form of β2-adrenergic receptor agonist
FR2855521B1 (fr) 2003-05-28 2005-08-05 Flamel Tech Sa Polyaminoacides fonctionnalises par au moins un groupement h ydrophobe et leurs applications notamment therapeutiques.
CN1795181A (zh) 2003-05-29 2006-06-28 麦克公司 用作11β－羟基类固醇脱氢酶－1抑制剂的三唑衍生物
AU2003902828A0 (en) 2003-06-05 2003-06-26 Fujisawa Pharmaceutical Co., Ltd. Dpp-iv inhibitor
JP2004359630A (ja) 2003-06-06 2004-12-24 Yamanouchi Pharmaceut Co Ltd ジフルオロジフェニルメタン誘導体及びその塩
DE10327439A1 (de) 2003-06-18 2005-01-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Imidazopyridazinon- und Imidazopyridonderivate, deren Herstellung und deren Verwendung als Arzneimittel
US7566707B2 (en) 2003-06-18 2009-07-28 Boehringer Ingelheim International Gmbh Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
RU2339636C2 (ru) 2003-06-20 2008-11-27 Ф.Хоффманн-Ля Рош Аг Гексагидропиридоизохинолины в качестве ингибиторов дипептидилпептидазы iv (dpp-iv)
JP4708187B2 (ja) 2003-06-20 2011-06-22 キッセイ薬品工業株式会社 ピラゾール誘導体、それを含有する医薬組成物及びその製造中間体
WO2005000848A1 (en) 2003-06-20 2005-01-06 F. Hoffmann-La Roche Ag Pyrido` 2, 1-a - isoquinoline derivatives as dpp-iv inhibitors
WO2004113345A1 (ja) 2003-06-20 2004-12-29 Japan Tobacco Inc. 縮合ピロール化合物及びその医薬用途
JO2625B1 (en) 2003-06-24 2011-11-01 ميرك شارب اند دوم كوربوريشن Phosphoric acid salts of dipeptidyl betidase inhibitor 4
WO2004113310A1 (en) 2003-06-25 2004-12-29 Biovitrum Ab Use of an inhibitor of 11-b-hydroxysteroid dehydrogenase type 1 compounds for promoting wound healing
US7364755B2 (en) 2003-07-07 2008-04-29 Synthon Ip Inc. Modified calcium phosphate excipient
AR045047A1 (es) 2003-07-11 2005-10-12 Arena Pharm Inc Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos
JP4920410B2 (ja) 2003-07-14 2012-04-18 アリーナ ファーマシューティカルズ， インコーポレイテッド 代謝モジュレーターとしての縮合アリールおよびヘテロアリール誘導体ならびに代謝に関連する障害の予防および治療
US20050027012A1 (en) 2003-07-16 2005-02-03 Boehringer Ingelheim International Gmbh Tablets containing ambroxol
DE60331236D1 (de) 2003-07-24 2010-03-25 Eswaran Krishnan Iyer Orale zusammensetzungen zur behandlung von diabetes
US6995183B2 (en) 2003-08-01 2006-02-07 Bristol Myers Squibb Company Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods
RU2355687C2 (ru) 2003-08-01 2009-05-20 Дженелэбс Текнолоджиз, Инк Бициклические производные имидазола в качестве средства против вирусов семейства flaviviridae
DE10335092B3 (de) 2003-08-01 2005-02-03 Aventis Pharma Deutschland Gmbh Substituierte Benzoylureido-o-benzoylamide, Verfahren zu deren Herstellung und deren Verwendung
CA2549022A1 (en) 2003-08-01 2005-02-10 Janssen Pharmaceutica N.V. Substituted benzimidazole-, benztriazole-, and benzimidazolone-o-glucosides
TW200521131A (en) 2003-08-01 2005-07-01 Janssen Pharmaceutica Nv Substituted fused heterocyclic c-glycosides
RS20060320A (en) 2003-08-01 2008-08-07 Janssen Pharmaceutica N.V., Substituted indazole-o-glucosides
ES2402098T5 (es) 2003-08-01 2021-06-09 Mitsubishi Tanabe Pharma Corp Compuestos novedosos que tienen actividad inhibidora frente a transportador dependiente de sodio
AR048282A1 (es) 2003-08-01 2006-04-19 Janssen Pharmaceutica Nv Indol- o - glucosidos sustituidos
GB0318463D0 (en) 2003-08-07 2003-09-10 Astrazeneca Ab Chemical compounds
US7659408B2 (en) 2003-08-07 2010-02-09 Merck Sharp & Dhome Corp. Pyrazole carboxamides as inhibitors of 11-β-hydroxysteroid dehydrogenase-1
GB0318464D0 (en) 2003-08-07 2003-09-10 Astrazeneca Ab Chemical compounds
CN1845753A (zh) 2003-08-14 2006-10-11 诺和诺德医疗保健公司 因子ⅶ多肽类的含水液体药物组合物
GB0319759D0 (en) 2003-08-22 2003-09-24 Astrazeneca Ab Chemical compounds
GB0319690D0 (en) 2003-08-22 2003-09-24 Astrazeneca Ab Chemical compounds
CA2539032A1 (en) 2003-08-26 2005-03-10 Boehringer Ingelheim International Gmbh Glucopyranosyloxy-pirazoles, drugs containing said compounds the use and production method thereof
WO2005020985A1 (en) 2003-08-29 2005-03-10 Astrazeneca Ab Indolamide derivatives which possess glycogen phosphorylase inhibitory activity
WO2005020986A1 (en) 2003-08-29 2005-03-10 Astrazeneca Ab Heterocyclic amide derivatives which posses glycogen phosphorylase inhibitory activity
US20070190022A1 (en) 2003-08-29 2007-08-16 Bacopoulos Nicholas G Combination methods of treating cancer
GB0320422D0 (en) 2003-08-30 2003-10-01 Astrazeneca Ab Chemical compounds
EP1699777B1 (en) 2003-09-08 2012-12-12 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
CA2540741A1 (en) 2003-10-03 2005-04-14 Takeda Pharmaceutical Company Limited Agent for treating diabetes
US7284625B2 (en) 2003-10-22 2007-10-23 Kirk Jones Quick connect assembly for ATV implements
CA2540843A1 (en) 2003-10-23 2005-05-12 Sterix Limited Phenyl carboxamide and sulfonamide derivatives for use as 11-beta-hydroxysteroid dehydrogenase
US20050091394A1 (en) 2003-10-27 2005-04-28 Schneider Automation Inc. Software configurable dual cable redundant Ethernet or bus configuration
BR0304443B1 (pt) 2003-10-28 2012-08-21 processo para obtenção de concentrados de titánio com elevado teor de tio2 e baixo teor de radionuclìdeos a partir de concentrados mecánicos de anatásio.
WO2005044192A2 (en) 2003-10-28 2005-05-19 Amgen Inc. Triazole compounds and uses related thereto
US7246174B2 (en) 2003-10-28 2007-07-17 Nacon Consulting, Llc Method and system for accessing and managing virtual machines
GB0325402D0 (en) 2003-10-31 2003-12-03 Astrazeneca Ab Compounds
GB0325745D0 (en) 2003-11-05 2003-12-10 Astrazeneca Ab Chemical compounds
GB0326029D0 (en) 2003-11-07 2003-12-10 Astrazeneca Ab Chemical compounds
US7107714B2 (en) 2003-11-10 2006-09-19 Marketing Displays, Inc. Portable snap-fit sign stand
EP2839832A3 (en) * 2003-11-17 2015-06-24 Novartis AG Use of dipeptidyl peptidase IV inhibitors
JP2005170939A (ja) 2003-11-20 2005-06-30 Takeda Chem Ind Ltd 糖尿病の予防・治療剤
EP1532980A1 (en) 2003-11-24 2005-05-25 Novo Nordisk A/S N-heteroaryl indole carboxamides and analogues thereof, for use as glucokinase activators in the treatment of diabetes
DE10355304A1 (de) 2003-11-27 2005-06-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
GB0327760D0 (en) 2003-11-29 2003-12-31 Astrazeneca Ab Compounds
GB0327761D0 (en) 2003-11-29 2003-12-31 Astrazeneca Ab Compounds
JPWO2005053695A1 (ja) 2003-12-04 2007-12-06 エーザイ・アール・アンド・ディー・マネジメント株式会社 多発性硬化症予防剤または治療剤
GB0328178D0 (en) 2003-12-05 2004-01-07 Astrazeneca Ab Compounds
US7217711B2 (en) 2003-12-17 2007-05-15 Boehringer Ingelheim International Gmbh Piperazin-1-yl and 2-([1,4]diazepan-1-yl)-imidazo[4,5-d]-pyridazin-4-ones, the preparation thereof and their use as pharmaceutical compositions
DE10359098A1 (de) 2003-12-17 2005-07-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 2-(Piperazin-1-yl)- und 2-([1,4]Diazepan-1-yl)-imidazo[4,5-d]pyridazin-4-one, deren Herstellung und deren Verwendung als Arzneimittel
CN1894239A (zh) 2003-12-18 2007-01-10 泰博特克药品有限公司 作为呼吸道合胞病毒复制的抑制剂的哌啶－氨基－苯并咪唑类衍生物
EP1696915A1 (en) 2003-12-19 2006-09-06 Pfizer, Inc. Benzenesulfonylamino-pyridin-2-yl derivatives and related compounds as inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-hsd-1) for the treatment of diabetes and obesity
EP1703908A4 (en) 2003-12-22 2009-07-08 Amgen Inc ARYLSULFONAMIDE COMPOUNDS AND RELATED APPLICATIONS
DE10361133A1 (de) 2003-12-22 2005-07-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg Glucopyranosyloxy-substituierte Aromaten, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE10360835A1 (de) 2003-12-23 2005-07-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg Bicyclische Imidazolverbindungen, deren Herstellung und deren Verwendung als Arzneimittel
EP1711491A1 (en) 2003-12-24 2006-10-18 Prosidion Limited Heterocyclic derivatives as gpcr receptor agonists
EP1702919B1 (en) 2003-12-29 2012-05-30 Msd K.K. Novel 2-heteroaryl-substituted benzimidazole derivative
MXPA06007715A (es) 2004-01-06 2007-01-26 Johnson & Johnson Derivados de (3-oxo-3,4-dihidro-quinoxalin-2-il-amino)-benzamida y compuesto relacionado, como inhibidores de glucogeno fosforilasa para el tratamiento de la diabetes y obesidad.
ES2399052T3 (es) 2004-01-06 2013-03-25 Novo Nordisk A/S Heteroaril-ureas y su uso como activadores de glucocinasa
JP4994043B2 (ja) 2004-01-21 2012-08-08 エランコ・アニマル・ヘルス・アイルランド・リミテッド ミトラタピデ経口用溶液
EP1711477A4 (en) 2004-01-26 2009-06-10 Merck & Co Inc NOVEL CRYSTALLINE FORMS OF AN INHIBITOR OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1
DE102004004972B3 (de) 2004-01-31 2005-09-15 Aventis Pharma Deutschland Gmbh Heterocyclisch substituierte 7-Amino-4-chinolon-3-carbonsäure-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
DE102004004971B3 (de) 2004-01-31 2005-09-15 Aventis Pharma Deutschland Gmbh Cycloalkyl substituierte 7-Amino-4-chinolon-3-carbonsäure-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arnzeimittel
JP2007519648A (ja) 2004-01-31 2007-07-19 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング ７−フェニルアミノ−４−キノロン−３−カルボン酸誘導体、その製造方法及び医薬としての使用
JP2005247834A (ja) 2004-02-04 2005-09-15 Taisho Pharmaceut Co Ltd ナトリウム依存性グルコース供輸送体２の活性阻害剤
US20050239853A1 (en) 2004-02-04 2005-10-27 Tjeerd Barf New compounds
SE0400234D0 (sv) 2004-02-06 2004-02-06 Active Biotech Ab New compounds, methods for their preparation and use thereof
US7501426B2 (en) 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
BRPI0507734A (pt) 2004-02-18 2007-07-10 Astrazeneca Ab composto ou um sal, pró-droga ou solvato do mesmo, método de tratar doenças mediadas por glk, e, processo para a preparação de um composto
ES2322709T3 (es) 2004-02-18 2009-06-25 Astrazeneca Ab Derivados de benzamida y su uso como agentes activadores de la glucocinasa.
WO2005085246A1 (de) 2004-02-18 2005-09-15 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthine, deren herstellung und deren verwendung als dpp-iv hemmer
DE102004019540A1 (de) 2004-04-22 2005-11-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Arzneimittelkombinationen zur Behandlung von Atemwegserkrankungen
DE102004009039A1 (de) 2004-02-23 2005-09-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel
ZA200606792B (en) 2004-03-04 2007-12-27 Kissei Pharmaceutical Fused heterocycle derivative, medicinal composition containing the same, and medicinal use thereof
WO2005085267A1 (ja) 2004-03-04 2005-09-15 Kissei Pharmaceutical Co., Ltd. 含窒素縮合環誘導体、それを含有する医薬組成物およびその医薬用途
NZ549629A (en) 2004-03-04 2010-06-25 Kissei Pharmaceutical Fused heterocycle derivative, medicinal composition containing the same, and medicinal use thereof
EP1593671A1 (en) 2004-03-05 2005-11-09 Graffinity Pharmaceuticals AG DPP-IV inhibitors
JP2007527904A (ja) 2004-03-08 2007-10-04 プロシディオン・リミテッド グリコーゲンホスホリラーゼ阻害剤としてのピロロピリジン−２−カルボン酸ヒドラジド化合物
WO2005085194A2 (en) 2004-03-08 2005-09-15 Prosidion Limited Indole-2-carboxylic acid hydrazides as glycogen phosphorylase inhibitors
US7393847B2 (en) 2004-03-13 2008-07-01 Boehringer Ingleheim International Gmbh Imidazopyridazinediones, their preparation and their use as pharmaceutical compositions
CN102140090A (zh) 2004-03-15 2011-08-03 武田药品工业株式会社 二肽基肽酶抑制剂
CN103467423B (zh) 2004-03-16 2016-03-16 贝林格尔.英格海姆国际有限公司 吡喃葡萄糖基取代的苯基衍生物、含该化合物的药物、其用途及其制造方法
EP1577306A1 (de) 2004-03-17 2005-09-21 Boehringer Ingelheim Pharma GmbH & Co.KG Neue Benzoxazinonderivate als langwirksame Betamimetika zur Behandlung von Atemwegserkrankungen
US7354938B2 (en) 2004-03-23 2008-04-08 Amgen Inc. Pyrazole compounds and uses related thereto
WO2005090332A1 (ja) 2004-03-23 2005-09-29 Banyu Pharmaceutical Co., Ltd 置換キナゾリン又はピリドピリミジン誘導体
EP1732904B1 (en) 2004-03-29 2014-03-19 Merck Sharp & Dohme Corp. Diaryltriazoles as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1
WO2005095372A1 (ja) 2004-03-31 2005-10-13 Kissei Pharmaceutical Co., Ltd. ナフタレン誘導体、それを含有する医薬組成物及びその医薬用途
WO2005095429A1 (ja) 2004-03-31 2005-10-13 Kissei Pharmaceutical Co., Ltd. フェノール誘導体、それを含有する医薬組成物及びその医薬用途
JPWO2005095373A1 (ja) 2004-03-31 2008-02-21 キッセイ薬品工業株式会社 ナフタレン誘導体、それを含有する医薬組成物およびその医薬用途
BRPI0509573A (pt) 2004-04-02 2007-09-25 Novartis Ag derivados de sulfonamida-tiazolpiridina como ativadores de glicocinase úteis para o tratamento de diabetes do tipo 2
MXPA06011365A (es) 2004-04-02 2006-12-15 Novartis Ag Derivados de tiazolo-piridina, composiciones farmaceuticas que los contienen, y metodos para el tratamiento de condiciones mediadas por glucoquinasa.
JP2007261945A (ja) 2004-04-07 2007-10-11 Taisho Pharmaceut Co Ltd チアゾール誘導体
JP2007531780A (ja) 2004-04-10 2007-11-08 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規な２−アミノ−イミダゾ［４，５−ｄ］ピリダジン−４−オン及び２−アミノ−イミダゾ［４，５−ｃ］ピリダジン−４−オン、その製法及び医薬としての使用
US7179809B2 (en) 2004-04-10 2007-02-20 Boehringer Ingelheim International Gmbh 2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
US7402704B2 (en) 2004-04-14 2008-07-22 Amgen Inc. Arylsulfones and uses related thereto
GB0408771D0 (en) 2004-04-20 2004-05-26 Sterix Ltd Compound
JP2007533749A (ja) 2004-04-20 2007-11-22 アムゲン インコーポレイティッド アリールスルホンアミドおよびそれに関連する使用方法
US20080242869A1 (en) 2004-04-21 2008-10-02 Matthew Fyfe Tri(Cyclo) Substituted Amide Compounds
US20050239778A1 (en) 2004-04-22 2005-10-27 Boehringer Ingelheim International Gmbh Novel medicament combinations for the treatment of respiratory diseases
US20050244502A1 (en) 2004-04-28 2005-11-03 Mathias Neil R Composition for enhancing absorption of a drug and method
US20050245533A1 (en) 2004-04-29 2005-11-03 Hoff Ethan D Inhibitors of the 11-beta-hydroxysteroid dehydrogenaseType 1 enzyme and their therapeutic application
US20050261302A1 (en) 2004-04-29 2005-11-24 Hoff Ethan D Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their therapeutic application
US20050245534A1 (en) 2004-04-29 2005-11-03 Link James T Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
US7880001B2 (en) 2004-04-29 2011-02-01 Abbott Laboratories Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
US20050245532A1 (en) 2004-04-29 2005-11-03 Hoff Ethan D Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their therapeutic application
AU2005240122B2 (en) * 2004-05-03 2011-02-17 Omega Bio-Pharma (I.P.3) Limited Cysteamines for treating complications of hypercholesterolemia and diabetes
JP2007536369A (ja) 2004-05-06 2007-12-13 ファイザー・インク プロリン及びモルホリン誘導体の新規化合物
MXPA06012929A (es) 2004-05-07 2007-01-26 Janssen Pharmaceutica Nv Derivados de adamantil pirrolidin-2-ona como inhibidores de 11-beta hidroxiesteroide deshidrogenasa.
TWI350168B (en) 2004-05-07 2011-10-11 Incyte Corp Amido compounds and their use as pharmaceuticals
NZ551077A (en) 2004-05-07 2009-05-31 Janssen Pharmaceutica Nv Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors
US7439370B2 (en) 2004-05-10 2008-10-21 Boehringer Ingelheim International Gmbh Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
NZ550229A (en) 2004-05-12 2009-07-31 Pfizer Prod Inc Proline derivatives and their use as dipeptidyl peptidase IV inhibitors
DE102004024454A1 (de) 2004-05-14 2005-12-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Enantiomerenreine Betaagonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
PE20060315A1 (es) 2004-05-24 2006-05-15 Irm Llc Compuestos de tiazol como moduladores de ppar
ATE417837T1 (de) 2004-05-24 2009-01-15 Amgen Inc Inhibitoren von 11-beta- hydroxysteroiddehydrogenase typ 1
TWI415635B (zh) 2004-05-28 2013-11-21 必治妥施貴寶公司 加衣錠片調製物及製備彼之方法
BRPI0510527A (pt) 2004-06-01 2007-10-30 Ares Trading Sa método de estabilização de proteìnas
EP1756740A1 (en) 2004-06-03 2007-02-28 Pfizer Products Inc. Crystal structure of dipeptidyl peptidase iv (dpp-iv) and uses thereof
US7935723B2 (en) 2004-06-04 2011-05-03 Novartis Pharma Ag Use of organic compounds
TW200600086A (en) 2004-06-05 2006-01-01 Astrazeneca Ab Chemical compound
EP1604989A1 (en) 2004-06-08 2005-12-14 Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft DPP-IV inhibitors
WO2005120576A2 (en) * 2004-06-09 2005-12-22 Yasoo Health Composition and method for improving pancreatic islet cell survival
DE102004028241B4 (de) 2004-06-11 2007-09-13 Sanofi-Aventis Deutschland Gmbh Neue Fluorglykosidderivate von Pyrazolen, diese Verbindungen enthaltende Arzneimittel und Herstellung dieser Arzneimittel
BRPI0512630A (pt) 2004-06-24 2008-03-25 Incyte Corp compostos de amido e seu uso como produtos farmacêuticos
US20060009491A1 (en) 2004-06-24 2006-01-12 Incyte Corporation Amido compounds and their use as pharmaceuticals
AU2005267289A1 (en) 2004-06-24 2006-02-02 Incyte Corporation N-substituted piperidines and their use as pharmaceuticals
DE102004030502A1 (de) 2004-06-24 2006-01-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel
KR20070024639A (ko) 2004-06-24 2007-03-02 인사이트 산 디에고 인코포레이티드 아미도 화합물 및 약제로서의 이의 용도
CA2570694A1 (en) 2004-06-24 2006-02-02 Incyte Corporation Amido compounds and their use as pharmaceuticals
WO2006000371A2 (en) 2004-06-28 2006-01-05 F.Hoffmann-La Roche Ag Pyrimidine derivatives as 11beta-hsd1 inhibitors
US7393836B2 (en) 2004-07-06 2008-07-01 Boehringer Ingelheim International Gmbh D-xylopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture
CA2511269A1 (en) * 2004-07-07 2006-01-07 F. Hoffmann-La Roche Ag Multimarker panel based on p1gf for diabetes type 1 and 2
MX2007000507A (es) 2004-07-14 2007-03-08 Novartis Ag Combinacion de inhibidores de dpp-iv y compuestos que modulan a los receptores 5-ht3 y/o 5-ht4.
DE102004034690A1 (de) 2004-07-17 2006-02-02 Boehringer Ingelheim Pharma Gmbh & Co. Kg Methyliden-D-xylopyranosyl-und Oxo-D-xylopyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
TW200606129A (en) 2004-07-26 2006-02-16 Chugai Pharmaceutical Co Ltd Novel cyclohexane derivative, its prodrug, its salt and diabetic therapeutic agent containing the same
EP1773800A1 (de) 2004-07-27 2007-04-18 Boehringer Ingelheim International GmbH D-glucopyranosyl-phenyl-substituierte cyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
DK1789041T3 (da) 2004-07-28 2008-09-08 Hoffmann La Roche Aryl-pyridinderivater som 11-beta-HSD1-inhibitorer
US20060025445A1 (en) 2004-08-02 2006-02-02 Xiang Jason S 11-Beta HSD1 inhibitors
CN1993320A (zh) 2004-08-06 2007-07-04 默克公司 作为11－β－羟基类固醇脱氢酶－1的抑制剂的磺酰化合物
JP2006045156A (ja) 2004-08-06 2006-02-16 Sumitomo Pharmaceut Co Ltd 縮合ピラゾール誘導体
WO2006020598A2 (en) 2004-08-10 2006-02-23 Incyte Corporation Amido compounds and their use as pharmaceuticals
WO2006018150A1 (de) 2004-08-11 2006-02-23 Boehringer Ingelheim International Gmbh D-xylopyranosyl-phenyl-substituierte cyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
GB0418046D0 (en) 2004-08-12 2004-09-15 Prosidion Ltd Eantioselective process
CN101035767A (zh) 2004-08-12 2007-09-12 普洛希典有限公司 被取代的苯乙酰胺及其作为葡糖激酶激活剂的用途
GB0418058D0 (en) 2004-08-12 2004-09-15 Prosidion Ltd Fluorination process
TW200613275A (en) 2004-08-24 2006-05-01 Recordati Ireland Ltd Lercanidipine salts
US20070259927A1 (en) 2004-08-26 2007-11-08 Takeda Pharmaceutical Company Limited Remedy for Diabetes
EA012263B1 (ru) 2004-08-30 2009-08-28 Янссен Фармацевтика Н.В. Производные n-2-адамантанил-2-феноксиацетамида в качестве ингибиторов 11-бета-гидроксистероид-дегидрогеназы
CN101039908B (zh) 2004-08-30 2010-06-23 詹森药业有限公司 作为11-β羟甾类脱氢酶抑制剂的三环内酰胺衍生物
DE102004043944A1 (de) 2004-09-11 2006-03-30 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 8-(3-Amino-piperidin-1-yl)-7-(but-2-inyl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
DE102004044221A1 (de) 2004-09-14 2006-03-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 3-Methyl-7-butinyl-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
US7776897B2 (en) 2004-09-16 2010-08-17 Astellas Pharma Inc. Triazole derivative or salt thereof
JP4671648B2 (ja) 2004-09-17 2011-04-20 株式会社ソニー・コンピュータエンタテインメント 中継器、エンタテインメント装置、通信システム、通信方法、及びプログラム
CN1759834B (zh) 2004-09-17 2010-06-23 中国医学科学院医药生物技术研究所 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途
AR051446A1 (es) 2004-09-23 2007-01-17 Bristol Myers Squibb Co Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2)
WO2006036664A1 (en) 2004-09-23 2006-04-06 Amgen Inc. Substituted sulfonamidopropionamides and methods of use
EP1803729A4 (en) 2004-09-29 2008-10-01 Kissei Pharmaceutical HETEROCYCLIC NITROGENIC COMPOUND 1- (-D-GLYCOPYRANOSYL) -3-SUBSTITUTED, THERAPEUTIC PREPARATION CONTAINING SAID COMPOUND, AND MEDICAL USE OF SAID COMPOUND
DE102004048388A1 (de) 2004-10-01 2006-04-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg D-Pyranosyl-substituierte Phenyle, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
NZ554014A (en) 2004-10-04 2010-06-25 Hoffmann La Roche Alkil-pyridines as 11-beta inhibitors for diabetes
JP2008515905A (ja) 2004-10-08 2008-05-15 ノバルティス アクチエンゲゼルシャフト 有機化合物の組合せ剤
WO2006040329A1 (en) 2004-10-12 2006-04-20 Novo Nordisk A/S 1 ibeta- hydroxysteroid dehydrogenase type 1 active spiro compounds
WO2006040625A1 (en) 2004-10-12 2006-04-20 Glenmark Pharmaceuticals S.A. Novel dipeptidyl peptidase iv inhibitors, pharmaceutical compositions containing them, and process for their preparation
GB0423044D0 (en) 2004-10-16 2004-11-17 Astrazeneca Ab Compounds
GB0423043D0 (en) 2004-10-16 2004-11-17 Astrazeneca Ab Compounds
KR20070068407A (ko) 2004-10-25 2007-06-29 노파르티스 아게 Ｄｐｐ―ｉｖ 억제제, ｐｐａｒ 항당뇨병제 및메트포르민의 조합물
ES2318577T3 (es) 2004-10-29 2009-05-01 Eli Lilly And Company Derivados de cicloalquil lactama como inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1'.
WO2006048750A2 (en) 2004-11-02 2006-05-11 Pfizer Inc. Novel compounds of substituted and unsubstituted adamantyl amides
WO2006049304A1 (ja) 2004-11-02 2006-05-11 Banyu Pharmaceutical Co., Ltd アリールオキシ置換ベンズイミダゾール誘導体
DE102005013967A1 (de) 2004-11-05 2006-10-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Bradykinin-B1-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102004054054A1 (de) 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
EP1655283A1 (en) 2004-11-08 2006-05-10 Evotec OAI AG 11beta-HSD1 Inhibitors
EP1659113A1 (en) 2004-11-08 2006-05-24 Evotec AG Inhibitors of 11beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1)
EP1666467A1 (en) 2004-11-08 2006-06-07 Evotec AG 11Beta-HSD1 Inhibitors
MX2007005590A (es) 2004-11-09 2007-05-24 Smithkline Beecham Corp Compuestos del inhibidor glicogeno fosforilasa y sus composiciones farmaceuticas.
WO2006051662A1 (ja) 2004-11-09 2006-05-18 Taisho Pharmaceutical Co., Ltd. チアゾール誘導体
JP2006137678A (ja) 2004-11-10 2006-06-01 Shionogi & Co Ltd インターロイキン−２組成物
NZ554906A (en) 2004-11-10 2011-01-28 Incyte Corp Lactam compounds and their use as pharmaceuticals
WO2006053274A2 (en) 2004-11-15 2006-05-18 Bristol-Myers Squibb Company 2-amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors
US7226942B2 (en) 2004-11-15 2007-06-05 Bristol-Myers Squibb Company 2-amino-4-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors
WO2006055435A1 (en) 2004-11-15 2006-05-26 Bristol-Myers Squibb Company 2-aminonaphthalene derivatives and related glycogen phosphorylase inhibitors
WO2006055463A2 (en) 2004-11-15 2006-05-26 Bristol-Myers Squibb Company 2-amino-3-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors
CN101103016A (zh) 2004-11-18 2008-01-09 因塞特公司 11-β羟基类固醇脱氢酶1型抑制剂及其使用方法
CA2588963C (en) 2004-11-18 2013-06-25 Kissei Pharmaceutical Co., Ltd. 1-substituted-3-.beta.-d-glucopyranosylated nitrogenous hetero-cyclic compounds and medicines containing the same
GB0425919D0 (en) 2004-11-25 2004-12-29 Prosidion Ltd Indole-2-carboxylic acid amides
WO2006059163A1 (en) 2004-12-02 2006-06-08 Prosidion Limited Treatment of diabetes with glycogen phosphorylase inhibitors
WO2006059164A2 (en) 2004-12-02 2006-06-08 Prosidion Limited Pyrrolopyridine-2-carboxylic acid amides
PL1819704T3 (pl) 2004-12-02 2008-12-31 Prosidion Ltd Amidowe pochodne kwasu pirolopirydyno-2-karboksylowego użyteczne jako inhibitory fosforylazy glikogenowej
MX2007006420A (es) 2004-12-03 2007-07-19 Novo Nordisk As Activadores heteroaromaticos de glucocinasa.
JP2008007405A (ja) 2004-12-07 2008-01-17 Takeda Chem Ind Ltd カルボキサミド誘導体
DE602005009745D1 (de) 2004-12-16 2008-10-23 Boehringer Ingelheim Pharma Glucopyranosyl-substituierte benzen-derivate, medikamente mit solchen verbindungen, ihre verwendung und herstellungsverfahren dafür
WO2006066109A2 (en) 2004-12-17 2006-06-22 Takeda San Diego, Inc. Hydroxysteroid dehydrogenase inhibitors
ES2308602T3 (es) 2004-12-20 2008-12-01 Eli Lilly And Company Derivados de cicloalquil lactamas como inhibidores de la 11-beta-hidroxiesteroide deshidrogenasa 1.
WO2006068991A1 (en) 2004-12-21 2006-06-29 Eli Lilly And Company Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
WO2006068199A1 (ja) 2004-12-22 2006-06-29 Mochida Pharmaceutical Co., Ltd. 代謝的に安定な３－オキシ－１，２，４－トリアゾール誘導体
RU2382786C2 (ru) 2004-12-24 2010-02-27 ДАЙНИППОН СУМИТОМО ФАРМА Ко., ЛТД. Бициклические производные пиррола
KR100760430B1 (ko) 2004-12-31 2007-10-04 한미약품 주식회사 당뇨병 치료제의 경구 투여용 서방성 복합 제제 및 이의제조 방법
AU2006203918B2 (en) 2005-01-05 2011-05-19 Abbvie Inc. Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
NZ555966A (en) 2005-01-05 2011-03-31 Abbott Lab Adamantyl derivatives as inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
US20060148871A1 (en) 2005-01-05 2006-07-06 Rohde Jeffrey J Metabolic stabilization of substituted adamantane
TW200637839A (en) 2005-01-07 2006-11-01 Taisho Pharmaceutical Co Ltd 1-thio-d-glucitol derivatives
DOP2006000008A (es) 2005-01-10 2006-08-31 Arena Pharm Inc Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1
MY148521A (en) 2005-01-10 2013-04-30 Arena Pharm Inc Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto
GT200600008A (es) 2005-01-18 2006-08-09 Formulacion de compresion directa y proceso
TW200637869A (en) 2005-01-28 2006-11-01 Chugai Pharmaceutical Co Ltd The spiroketal derivatives and the use as therapeutical agent for diabetes of the same
AR053329A1 (es) 2005-01-31 2007-05-02 Tanabe Seiyaku Co Derivados de indol utiles como inhibidores de los transportadores de glucosa dependientes del sodio (sglt)
JPWO2006080533A1 (ja) 2005-01-31 2008-06-19 持田製薬株式会社 ３−アミノ−１，２，４−トリアゾール誘導体
JP2008528666A (ja) 2005-02-05 2008-07-31 アストラゼネカ アクチボラグ グリコーゲンホスホリラーゼ阻害活性を有するインダンアミド誘導体
EP1848721A1 (en) 2005-02-05 2007-10-31 AstraZeneca AB Chemical compounds
CA2597269A1 (en) 2005-02-15 2006-08-24 Kissei Pharmaceutical Co., Ltd. 1-substituted-7-(beta-d-glycopyranosyloxy)(aza)indole compound and pharmaceutical containing the same
WO2006094633A1 (en) 2005-03-03 2006-09-14 F. Hoffman-La Roche Ag 1- sulfonyl-pi perdine- 3 -carboxyl i c acid amide derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase for the treatment of type ii diabetes mellitus
WO2006095822A1 (ja) 2005-03-11 2006-09-14 Ono Pharmaceutical Co., Ltd. スルホンアミド化合物およびその医薬
EP1868685A2 (en) 2005-03-18 2007-12-26 onepharm GmbH 11ß-HYDROXYSTEROID DEHYDROGENASES
GB0506133D0 (en) 2005-03-24 2005-05-04 Sterix Ltd Compound
JP5140577B2 (ja) 2005-03-31 2013-02-06 タケダ カリフォルニア インコーポレイテッド ヒドロキシステロイドデヒドロゲナーゼ阻害剤
EP1864971A4 (en) 2005-03-31 2010-02-10 Takeda Pharmaceutical PROPHYLACTIC / THERAPEUTIC AGENT AGAINST DIABETES
ES2369389T3 (es) 2005-04-05 2011-11-30 F. Hoffmann-La Roche Ag 1h-pirazol-4-carboxamidas, su preparación y su empleo como inhibidores de 11-beta- hidroxiesteroide dehidrogenasa.
WO2006106423A2 (en) 2005-04-07 2006-10-12 Pfizer Inc. Amino sulfonyl derivatives as inhibitors of human 11-.beta.-hydrosysteroid dehydrogenase
EP2527337A1 (en) 2005-04-14 2012-11-28 Bristol-Myers Squibb Company Inhibitors of 11-beta hydroxysteroid dehydrogenase type I
ES2338041T3 (es) 2005-04-15 2010-05-03 Boehringer Ingelheim International Gmbh Derivados de (heteroariloxi-bencil)-benceno sustituidos con glucopiranosilo en calidad de inhibidores de sglt.
EP1873144B1 (en) 2005-04-20 2014-07-23 Takeda Pharmaceutical Company Limited Fused heterocyclic compound
US20090305964A1 (en) 2005-04-21 2009-12-10 Gastrotech Pharma A/S Pharmaceutical preparations of a glp-1 molecule and an anti-emetic drug
EA200702208A1 (ru) 2005-04-22 2008-04-28 Алантос Фармасьютиклз Холдинг, Инк. Ингибиторы дипептидилпептидазы-iv
CN100539942C (zh) 2005-04-25 2009-09-16 株式会社日立制作所 利用磁共振的检查装置及核磁共振信号接收用线圈
UA91546C2 (uk) 2005-05-03 2010-08-10 Бьорінгер Інгельхайм Інтернаціональ Гмбх КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ
EP1884513A4 (en) 2005-05-23 2010-04-28 Japan Tobacco Inc PYRAZOLE COMPOUND AND THERAPEUTIC AGENT FOR DIABETES COMPRISING THE SAME
JP2008542247A (ja) 2005-05-24 2008-11-27 アストラゼネカ アクチボラグ グルコキナーゼモジュレーターとしての２−フェニル置換イミダゾール［４，５ｂ］ピリジン／ピラジンおよびプリン誘導体
CN101203494A (zh) 2005-05-25 2008-06-18 惠氏公司 合成经取代3-氰基喹啉和其中间物的方法
TW200714597A (en) 2005-05-27 2007-04-16 Astrazeneca Ab Chemical compounds
PT1894567E (pt) 2005-06-03 2012-11-21 Mitsubishi Tanabe Pharma Corp Agentes farmacêuticos concomitantes e sua utilização
EP1894919B1 (en) 2005-06-07 2012-03-28 Shionogi & Co., Ltd. Heterocyclic compound having type i 11 beta hydroxysteroid dehydrogenase inhibitory activity
WO2006132436A1 (ja) 2005-06-08 2006-12-14 Japan Tobacco Inc. 複素環化合物
US7572807B2 (en) 2005-06-09 2009-08-11 Bristol-Myers Squibb Company Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors
US7579360B2 (en) 2005-06-09 2009-08-25 Bristol-Myers Squibb Company Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors
GT200600218A (es) 2005-06-10 2007-03-28 Formulación y proceso de compresión directa
CA2610903A1 (en) 2005-06-16 2006-12-21 Pfizer Inc. N-(pyridin-2-yl)-sulfonamide derivatives
WO2006134481A1 (en) 2005-06-16 2006-12-21 Pfizer Inc. Inhibitors of 11-beta hydroxysteroid dehydrogenase type 1
US7605289B2 (en) 2005-06-17 2009-10-20 Amgen, Inc. Benzamide derivatives and uses related thereto
MX2007015848A (es) 2005-06-20 2008-04-22 Decode Genetics Ehf Variantes geneticas en el gen tcf7l2 como marcadores de diagnostico para el riesgo de diabetes mellitus tipo 2.
JP5112307B2 (ja) 2005-07-01 2013-01-09 メルク・シャープ・エンド・ドーム・コーポレイション Ｃｅｔｐ阻害剤を合成するための方法
UA94052C2 (uk) 2005-07-05 2011-04-11 Ф. Хоффманн-Ля Рош Аг Похідні піридазину
JP2009500378A (ja) 2005-07-08 2009-01-08 ノボ・ノルデイスク・エー／エス グルコキナーゼ活性化剤としてのジシクロアルキルカルバモイル尿素
WO2007006760A1 (en) 2005-07-08 2007-01-18 Novo Nordisk A/S Dicycloalkyl urea glucokinase activators
EP1904531B1 (en) 2005-07-08 2010-10-06 Pfizer Limited Madcam antibodies
JPWO2007007688A1 (ja) 2005-07-08 2009-01-29 持田製薬株式会社 ３，５−ジアミノ−１，２，４−トリアゾール誘導体
EP1910350A1 (en) 2005-07-09 2008-04-16 AstraZeneca AB 2 -heterocyclyloxybenzoyl amino heterocyclyl compounds as modulators of glucokinase for the treatment of type 2 diabetes
EP2027113A1 (en) 2005-07-09 2009-02-25 AstraZeneca AB Heteroaryl benzamide derivatives for use as glk activators in the treatment of diabetes
US7642259B2 (en) 2005-07-09 2010-01-05 Astrazeneca Ab Heteroaryl benzamide derivatives for use as GLK activators in the treatment of diabetes
CN101218237B (zh) 2005-07-11 2012-03-28 田边三菱制药株式会社 肟衍生物及其制备方法
JP5281287B2 (ja) 2005-07-13 2013-09-04 Ｍｓｄ株式会社 ヘテロ環置換ベンズイミダゾール誘導体
KR101446973B1 (ko) 2005-07-14 2014-10-07 트랜스테크 파르마 엘엘씨 우레아 글루코키나제 활성제
WO2007013929A1 (en) 2005-07-22 2007-02-01 Amgen Inc. Aniline sulfonamide derivatives and their uses
UY29694A1 (es) 2005-07-28 2007-02-28 Boehringer Ingelheim Int Metodos para prevenir y tratar trastornos metabolicos y nuevos derivados de pirazol-o-glucosido
DE102005035891A1 (de) 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
WO2007017649A1 (en) 2005-08-09 2007-02-15 Astrazeneca Ab Heteroarylcarbamoylbenzene derivatives for the treatment of diabetes
EP1917001A2 (en) 2005-08-11 2008-05-07 F.Hoffmann-La Roche Ag Pharmaceutical composition comprising a dpp-iv inhibitor
US7622492B2 (en) 2005-08-31 2009-11-24 Hoffmann-La Roche Inc. Pyrazolones as inhibitors of 11β-hydroxysteroid dehydrogenase
EP1760076A1 (en) 2005-09-02 2007-03-07 Ferring B.V. FAP Inhibitors
MY159522A (en) 2005-09-14 2017-01-13 Takeda Pharmaceuticals Co Administration of dipeptidyl peptidase inhibitors
EA015169B1 (ru) 2005-09-14 2011-06-30 Такеда Фармасьютикал Компани Лимитед Применение ингибиторов дипептидилпептидазы
JP2009508861A (ja) 2005-09-16 2009-03-05 アリーナ ファーマシューティカルズ， インコーポレイテッド 代謝の調節因子および代謝に関連する障害の処置
JP5072848B2 (ja) 2005-09-20 2012-11-14 ノバルティス アーゲー 低血糖イベントを低減するためのｄｐｐ−ｉｖ阻害剤の使用
WO2007038979A1 (en) 2005-09-22 2007-04-12 Swissco Development Ag Effervescent metformin composition and tablets and granules made therefrom
JOP20180109A1 (ar) 2005-09-29 2019-01-30 Novartis Ag تركيبة جديدة
AU2006297130B2 (en) 2005-09-30 2009-12-24 Novartis Ag DPP IV inhibitor for use in the treatment of autoimmune diseases and graft rejection
AU2006306420A1 (en) 2005-10-25 2007-05-03 Merck Sharp & Dohme Corp. Combination of a dipeptidyl peptidase-4 inhibitor and an anti-hypertensive agent for the treatment of diabetes and hypertension
EP1943301A4 (en) 2005-11-04 2010-01-13 Ls Corp SYNTHESIS OF MDH POLYMER HYBRID PARTICLES
JP5165582B2 (ja) 2005-12-16 2013-03-21 メルク・シャープ・エンド・ドーム・コーポレイション ジペプチジルペプチダーゼ−４インヒビターとメトホルミンとを組み合わせた医薬組成物
CA2633484A1 (en) 2005-12-23 2007-06-28 Novartis Ag Condensed heterocyclic compounds useful as dpp-iv inhibitors
GB0526291D0 (en) 2005-12-23 2006-02-01 Prosidion Ltd Therapeutic method
KR20080086483A (ko) 2006-01-06 2008-09-25 노파르티스 아게 유기 화합물의 용도
KR20080102395A (ko) 2006-02-15 2008-11-25 베링거 인겔하임 인터내셔날 게엠베하 글루코피라노실-치환된 벤조니트릴 유도체, 당해 화합물을 함유하는 약제학적 조성물, 이들의 용도 및 이들의 제조방법
WO2007099345A1 (en) 2006-03-02 2007-09-07 Betagenon Ab Medical use of bmp-2 and/ or bmp-4
PE20071221A1 (es) 2006-04-11 2007-12-14 Arena Pharm Inc Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas
US8455435B2 (en) 2006-04-19 2013-06-04 Ludwig-Maximilians-Universitat Munchen Remedies for ischemia
NO347644B1 (no) 2006-05-04 2024-02-12 Boehringer Ingelheim Int Polymorfer
PE20080251A1 (es) * 2006-05-04 2008-04-25 Boehringer Ingelheim Int Usos de inhibidores de dpp iv
EP1852108A1 (en) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
KR20070111099A (ko) 2006-05-16 2007-11-21 영진약품공업주식회사 시타글립틴 염산염의 신규 결정형, 이의 제조 방법과 이를포함하는 약학적 조성물
EA016995B1 (ru) 2006-05-16 2012-09-28 Джилид Сайэнс, Инк. Соль карбоновой кислоты фосфонамидного производного 2,6-диаминопурина, способы и средства для лечения новообразований и лечения злокачественных новообразований крови, набор, стерильный водный раствор и композиция
US20080064717A1 (en) 2006-05-19 2008-03-13 Rajesh Iyengar Inhibitors of diacylglycerol O-acyltransferase type 1 enzyme
KR100858848B1 (ko) 2006-05-23 2008-09-17 한올제약주식회사 메트포르민 서방정
WO2007149797A2 (en) 2006-06-19 2007-12-27 Novartis Ag Use of organic compounds
WO2007148185A2 (en) 2006-06-21 2007-12-27 Pfizer Products Inc. Substituted 3 -amino- pyrrolidino-4 -lactams as dpp inhibitors
AT503443B1 (de) 2006-06-23 2007-10-15 Leopold Franzens Uni Innsbruck Verfahren zur herstellung einer eisfläche für eissportbahnen
TW200811140A (en) 2006-07-06 2008-03-01 Arena Pharm Inc Modulators of metabolism and the treatment of disorders related thereto
TW200811147A (en) 2006-07-06 2008-03-01 Arena Pharm Inc Modulators of metabolism and the treatment of disorders related thereto
EP2057160A1 (en) 2006-08-08 2009-05-13 Boehringer Ingelheim International GmbH Pyrrolo [3, 2 -d]pyrimidines as dpp-iv inhibitors for the treatment of diabetes mellitus
CA2656847A1 (en) 2006-08-15 2008-02-21 Boehringer Ingelheim International Gmbh Glucopyranosyl-substituted cyclopropylbenzene derivatives, pharmaceutical compositions containing such compounds, their use as sglt inhibitors and process for their manufacture
JP2010501010A (ja) 2006-08-17 2010-01-14 ウェルスタット セラピューティクス コーポレイション 代謝障害のための併用処置
DE102006042586B4 (de) 2006-09-11 2014-01-16 Betanie B.V. International Trading Verfahren zum mikropartikulären Beladen von hochpolymeren Kohlenhydraten mit hydrophoben Wirkflüssigkeiten
US7956201B2 (en) 2006-11-06 2011-06-07 Hoffman-La Roche Inc. Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one
AR063569A1 (es) 2006-11-06 2009-02-04 Boehringer Ingelheim Int Derivados de benzil- benzonitrilo sustituidos con glucopiranosilo medicamentos que contienen a compuestos de este tipo su uso u procedimiento para su fabricacion
CN101534815A (zh) 2006-11-09 2009-09-16 贝林格尔.英格海姆国际有限公司 使用sglt-2抑制剂的组合治疗及其药物组合物
CN101657471B (zh) 2006-12-06 2013-07-03 史密丝克莱恩比彻姆公司 二环化合物及其作为抗糖尿病药的用途
ES2319596B1 (es) 2006-12-22 2010-02-08 Laboratorios Almirall S.A. Nuevos derivados de los acidos amino-nicotinico y amino-isonicotinico.
US7638541B2 (en) 2006-12-28 2009-12-29 Metabolex Inc. 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine
PE20081849A1 (es) 2007-01-04 2009-01-26 Prosidion Ltd Derivados de piperidin-4-il-propoxi-benzamida como agonistas de gpcr
CL2008000133A1 (es) 2007-01-19 2008-05-23 Boehringer Ingelheim Int Composicion farmaceutica que comprende un compuesto derivado de pirazol-o-glucosido combinado con al menos un segundo agente terapeutico; y uso de la composicion para el tratamiento de diabetes mellitus, cataratas, neuropatia, infarto de miocardio, e
JP5284967B2 (ja) 2007-02-01 2013-09-11 武田薬品工業株式会社 打錠障害を生じない錠剤製剤
ZA200905621B (en) 2007-02-01 2010-10-27 Takeda Pharmaceutical Solid preparation comprising alogliptin and pioglitazone
ES2366000T3 (es) 2007-02-06 2011-10-14 Chelsea Therapeutics, Inc. Nuevos compuestos, métodos para su preparación y uso de los mismos.
WO2008113000A1 (en) 2007-03-15 2008-09-18 Nectid, Inc. Anti-diabetic combinations comprising a slow release biguanide composition and an immediate release dipeptidyl peptidase iv inhibitor composition
EP2143443B1 (en) 2007-04-03 2014-11-19 Mitsubishi Tanabe Pharma Corporation A combination of dipeptidyl peptidase iv inhibitor and sweetener for use in the treatment of obesity
EP2508141A1 (en) 2007-04-16 2012-10-10 Smith & Nephew, Inc. Powered surgical system
PE20090696A1 (es) 2007-04-20 2009-06-20 Bristol Myers Squibb Co Formas cristalinas de saxagliptina y procesos para preparar las mismas
EP2144902B1 (en) 2007-05-04 2012-05-16 Bristol-Myers Squibb Company [6,6]and [6,7]-bicyclic gpr119 g protein-coupled receptor agonists
ES2398478T5 (es) 2007-07-09 2016-02-25 Symrise Ag Sales solubles estables de ácido fenilbencimidazolsulfónico de pH 6,0 a menos de 6,8
JO3272B1 (ar) 2007-07-19 2018-09-16 Takeda Pharmaceuticals Co مستحضر صلب يشمل ألوجليبتين وميتفورمين هيدروكلوريد
UY31291A1 (es) 2007-08-16 2009-03-31 Composicion farmacéutica que comprende un derivado de pirazol-0-glucosido
PE20090603A1 (es) 2007-08-16 2009-06-11 Boehringer Ingelheim Int Composicion farmaceutica que comprende un inhibidor de sglt2 y un inhibidor de dpp iv
PE20090987A1 (es) 2007-08-16 2009-08-14 Boehringer Ingelheim Int Composicion farmaceutica que comprende un derivado de pirazol-o-glucosido
CL2008002427A1 (es) 2007-08-16 2009-09-11 Boehringer Ingelheim Int Composicion farmaceutica que comprende 1-cloro-4-(b-d-glucopiranos-1-il)-2-[4-((s)-tetrahidrofurano-3-iloxi)bencil]-benceno combinado con 1-[(4-metilquinazolin-2-il)metil]-3-metil-7-(2-butin-1-il)-8-(3-(r)-aminopiperidin-1-il)xantina; y su uso para tratar diabetes mellitus tipo 2.
CN101784278A (zh) 2007-08-17 2010-07-21 贝林格尔.英格海姆国际有限公司 用于治疗fab-相关的疾病的嘌呤衍生物
WO2009037719A1 (en) 2007-09-21 2009-03-26 Lupin Limited Novel compounds as dipeptidyl peptidase iv (dpp iv) inhibitors
CA2705539A1 (en) 2007-11-13 2009-05-22 Evec Inc. Monoclonal antibodies that bind to hgm-csf and medical compositions comprising same
CN107115523A (zh) 2007-11-16 2017-09-01 诺沃—诺迪斯克有限公司 包含glp‑1肽或毒蜥外泌肽‑4和基础胰岛素肽的药物组合物
CN101234105A (zh) 2008-01-09 2008-08-06 北京润德康医药技术有限公司 一种含有二甲双胍和维格列汀的药用组合物及其制备方法
US20090186086A1 (en) 2008-01-17 2009-07-23 Par Pharmaceutical, Inc. Solid multilayer oral dosage forms
CL2008003653A1 (es) 2008-01-17 2010-03-05 Mitsubishi Tanabe Pharma Corp Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica.
TW200936136A (en) 2008-01-28 2009-09-01 Sanofi Aventis Tetrahydroquinoxaline urea derivatives, their preparation and their therapeutic application
JP2011510986A (ja) 2008-02-05 2011-04-07 メルク・シャープ・エンド・ドーム・コーポレイション メトホルミン及びジペプチジルペプチダーゼ−ｉｖ阻害剤の併用医薬組成物
CN101959406A (zh) 2008-03-04 2011-01-26 默沙东公司 二甲双胍和二肽基肽酶-ⅳ抑制剂的组合的药物组合物
EA019752B1 (ru) 2008-03-05 2014-06-30 Такеда Фармасьютикал Компани Лимитед Гетероциклическое амидное соединение и его применение для лечения/профилактики диабета
US8551524B2 (en) 2008-03-14 2013-10-08 Iycus, Llc Anti-diabetic combinations
CN102026636B (zh) 2008-03-31 2014-07-16 赛马拜制药公司 氧亚甲基芳基化合物和其用途
AR071175A1 (es) 2008-04-03 2010-06-02 Boehringer Ingelheim Int Composicion farmaceutica que comprende un inhibidor de la dipeptidil-peptidasa-4 (dpp4) y un farmaco acompanante
CN101590007A (zh) 2008-05-27 2009-12-02 北京瑞伊人科技发展有限公司 一种盐酸二甲双胍/伏格列波糖降糖口服制剂组合物及其制备
PE20100156A1 (es) 2008-06-03 2010-02-23 Boehringer Ingelheim Int Tratamiento de nafld
BRPI0916997A2 (pt) 2008-08-06 2020-12-15 Boehringer Ingelheim International Gmbh Inibidor de dpp-4 e seu uso
UY32030A (es) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
EA031225B1 (ru) 2008-08-15 2018-12-28 Бёрингер Ингельхайм Интернациональ Гмбх Ингибиторы дпп-4 для заживления ран
JP2010053576A (ja) 2008-08-27 2010-03-11 Sumitomo Forestry Co Ltd 舗装用マット
AU2009290911A1 (en) 2008-09-10 2010-03-18 Boehringer Ingelheim International Gmbh Combination therapy for the treatment of diabetes and related conditions
UY32177A (es) 2008-10-16 2010-05-31 Boehringer Ingelheim Int Tratamiento de diabetes en pacientes con control glucémico insuficiente a pesar de la terapia con fármaco, oral o no, antidiabético
WO2010045656A2 (en) 2008-10-17 2010-04-22 Nectid, Inc. Novel sglt2 inhibitor dosage forms
CA2745037C (en) 2008-12-23 2020-06-23 Boehringer Ingelheim International Gmbh Salt forms of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8(3-(r)-amino-piperidin-1-yl)-xanthine
AR074990A1 (es) 2009-01-07 2011-03-02 Boehringer Ingelheim Int Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina
AR075204A1 (es) 2009-01-29 2011-03-16 Boehringer Ingelheim Int Inhibidores de dpp-4 y composiciones farmaceuticas que los comprenden, utiles para tratar enfermedades metabolicas en pacientes pediatricos, particularmente diabetes mellitus tipo 2
GEP20135962B (en) 2009-02-13 2013-11-11 Boehringer Ingelheim Int Pharmaceutical composition comprising sglt2 inhibitor, dpp-iv inhibitor, and optionally further antidiabetic agent; and usage thereof
KR20160143897A (ko) 2009-02-13 2016-12-14 베링거 인겔하임 인터내셔날 게엠베하 Ｄｐｐ－４ 억제제(리나글립틴)을 임의로 다른 당뇨병 치료제와 병용하여 포함하는 당뇨병 치료 약제
UY32427A (es) 2009-02-13 2010-09-30 Boheringer Ingelheim Internat Gmbh Composicion farmaceutica, forma farmaceutica, procedimiento para su preparacion, metodos de tratamiento y usos de la misma
TW201031661A (en) 2009-02-17 2010-09-01 Targacept Inc Fused benzazepines as neuronal nicotinic acetylcholine receptor ligands
EP2408780A2 (en) 2009-03-20 2012-01-25 Pfizer Inc. 3-oxa-7-azabicycloý3.3.1¨nonanes
US8815292B2 (en) 2009-04-27 2014-08-26 Revalesio Corporation Compositions and methods for treating insulin resistance and diabetes mellitus
EP2424507A4 (en) 2009-04-27 2012-10-24 Revalesio Corp COMPOSITIONS AND METHODS FOR THE TREATMENT OF INSULIN AND DIABETES RESISTANCE
US20120100221A1 (en) 2009-06-02 2012-04-26 Ranbaxy Laboratories Limited Pharmaceutical compositions containing a combination of an antihistamine and a decongestant
CA2764438A1 (en) 2009-06-15 2010-12-23 Merck Sharp & Dohme Corp. Pharmaceutical compositions of combinations of dipeptidyl peptidase-4 inhibitors with pioglitazone
WO2011011541A1 (en) 2009-07-21 2011-01-27 Henry Trong Le Ferric citrate dosage forms
UY32919A (es) 2009-10-02 2011-04-29 Boehringer Ingelheim Int Composición farmacéutica, forma de dosificación farmacéutica, procedimiento para su preparación, mé todos para su tratamiento y sus usos
KR101763659B1 (ko) 2009-10-02 2017-08-01 베링거 인겔하임 인터내셔날 게엠베하 Ｂｉ―1356 및 메트포르민을 포함하는 약제학적 조성물
JP5446716B2 (ja) 2009-10-21 2014-03-19 大正製薬株式会社 アルギニン及びカルニチン含有錠剤の製造方法
MX364651B (es) 2009-11-27 2019-05-03 Boehringer Ingelheim Int Gmbh Star Inhibidores de dpp-iv, tales como la linagliptina, y composiciones farmacéuticas o combinaciones que comprenden los mismos, para usarse en el tratamiento de pacientes diabéticos tipificados genéticamente.
JP2010070576A (ja) 2009-12-28 2010-04-02 Sato Pharmaceutical Co Ltd 速溶解性錠剤
TWI562775B (en) 2010-03-02 2016-12-21 Lexicon Pharmaceuticals Inc Methods of using inhibitors of sodium-glucose cotransporters 1 and 2
JP2013522279A (ja) 2010-03-18 2013-06-13 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 糖尿病及び関連状態の治療で用いるｇｐｒ１１９作動薬とｄｄｐ−ｉｖ阻害薬リナグリプチンの組合せ
KR101927068B1 (ko) 2010-05-05 2018-12-10 베링거 인겔하임 인터내셔날 게엠베하 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법
JP5826830B2 (ja) 2010-05-05 2015-12-02 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ピオグリタゾンとリナグリプチンを含む医薬製剤
ES2577930T3 (es) 2010-06-09 2016-07-19 Poxel Derivados de triazina para retrasar el inicio de la diabetes tipo 1
RU2012155890A (ru) 2010-06-22 2014-07-27 ТиДаблЮАй ФАРМАСЬЮТИКАЛЗ, ИНК. Композиции с контролируемым высвобождением с пониженным воздействием пищи
MX2012014247A (es) 2010-06-24 2013-01-18 Boehringer Ingelheim Int Terapia para la diabetes.
KR20130137624A (ko) 2010-09-03 2013-12-17 브리스톨-마이어스 스큅 컴퍼니 수용성 항산화제를 사용한 약물 제제
WO2012039420A1 (ja) 2010-09-21 2012-03-29 国立大学法人九州大学 動脈圧反射機能障害に関連した疾患を治療するためのバイオニック動脈圧反射システム
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
WO2012088682A1 (en) 2010-12-29 2012-07-05 Shanghai Fochon Pharmaceutical Co Ltd. 2-(3-aminopiperidin-1-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-5,7(3h,6h)-dione derivates as dipeptidyl peptidase iv(dpp-iv) inhibitors
AU2012212448B9 (en) 2011-02-01 2015-06-25 Astrazeneca Uk Limited Pharmaceutical formulations including an amine compound
UY33937A (es) 2011-03-07 2012-09-28 Boehringer Ingelheim Int Composiciones farmacéuticas que contienen inhibidores de dpp-4 y/o sglt-2 y metformina
AU2012252380B2 (en) 2011-05-10 2016-09-08 Sandoz Ag Polymorph of Linagliptin benzoate
EA030121B1 (ru) 2011-07-15 2018-06-29 Бёрингер Ингельхайм Интернациональ Гмбх Замещенные хиназолины, их получение и их применение в фармацевтических композициях
US20130172244A1 (en) 2011-12-29 2013-07-04 Thomas Klein Subcutaneous therapeutic use of dpp-4 inhibitor
EP2800803A1 (en) 2012-01-04 2014-11-12 The Procter and Gamble Company Active containing fibrous structures with multiple regions
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
JP6218811B2 (ja) 2012-05-14 2017-10-25 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
JP6224084B2 (ja) 2012-05-14 2017-11-01 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
JP6374862B2 (ja) 2012-05-24 2018-08-15 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 自己免疫性糖尿病、特に、ｌａｄａの治療に使用するためのｄｐｐ−４阻害剤としてのキサンチン誘導体
JP2015518843A (ja) 2012-05-25 2015-07-06 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 創傷、例えば、糖尿病性創傷の処置における、ｄｐｐ−４阻害剤と組み合わせてもよい生物活性物質としてのケラチン生成細胞の使用
WO2013179307A2 (en) 2012-05-29 2013-12-05 Mylan Laboratories Limited Stabilized pharmaceutical compositions of saxagliptin
BR112015003067A2 (pt) 2012-08-24 2017-07-04 Novartis Ag inibidores de nep para tratar doenças caracterizadas por alargamento ou remodelagem atrial
US20140100292A1 (en) 2012-10-09 2014-04-10 Boehringer Ingelheim International Gmbh Use of moisture-conditioned disintegrants or expanding agents in tablet manufacture for the selective adjustment of the mechanical properties, the dissolving kinetics and/or the water loading of the tablets
WO2014056942A1 (en) 2012-10-09 2014-04-17 Boehringer Ingelheim International Gmbh Use of selectively moisture-adjusted tabletting material in the production of mechanically stable tablets which contain at least one hydrate-forming active substance and/or adjuvant relevant to the mechanical stability of the tablets, particularly arginine-containing tablets
US9050302B2 (en) 2013-03-01 2015-06-09 Jazz Pharmaceuticals Ireland Limited Method of administration of gamma hydroxybutyrate with monocarboxylate transporters
MX2015011466A (es) 2013-03-15 2016-01-22 Boehringer Ingelheim Int Uso de linagliptina en terapia antidiabetica cardio-y renoprotectora.
EP4000608A1 (en) 2013-04-18 2022-05-25 Boehringer Ingelheim International GmbH Pharmaceutical composition, methods for treating and uses thereof
JP2016518438A (ja) 2013-05-17 2016-06-23 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ＤＰＰ−４阻害薬とα−グルコシダーゼ阻害薬との組合せ
US20140371243A1 (en) 2013-06-14 2014-12-18 Boehringer Ingelheim International Gmbh Medical use of a dpp-4 inhibitor
WO2015128453A1 (en) 2014-02-28 2015-09-03 Boehringer Ingelheim International Gmbh Medical use of a dpp-4 inhibitor
CN104130258B (zh) 2014-08-13 2016-06-01 广东东阳光药业有限公司 一种二聚体的转化方法
US20160106677A1 (en) 2014-10-17 2016-04-21 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
EP4233840A3 (en) 2016-06-10 2023-10-18 Boehringer Ingelheim International GmbH Combinations of linagliptin and metformin
CA3103992A1 (en) 2018-07-17 2020-01-23 Boehringer Ingelheim International Gmbh Cardiosafe antidiabetic therapy

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