TWI403325B - 1-(β-D-吡喃葡糖基)-4-甲基-3-〔5-(4-氟苯基)-2-噻吩基甲基〕苯半水合物之結晶型 - Google Patents
1-(β-D-吡喃葡糖基)-4-甲基-3-〔5-(4-氟苯基)-2-噻吩基甲基〕苯半水合物之結晶型 Download PDFInfo
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Description
本發明係關於有用於做為鈉依賴性葡萄糖轉運體(sodium-dependent glucose transporter)抑制劑之結晶型1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物、其製備與單離之方法、包含該化合物及醫藥上可接受之載劑的醫藥組成物、以及治療之醫藥方法。
專利WO2005/012326冊本揭露鈉依賴性葡萄糖轉運體(SGLT)抑制劑的化合物群,及該等化合物對於處理糖尿病、肥胖、糖尿病併發症等之治療用途。描述於專利WO2005/012326冊本之式(I)的1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯:
一般而言,為了商業用途,重要的是產物應具備良好的操作性質。另外,亦需要製造純質與結晶型之該產物,使配方可符合嚴格的醫藥上的要求與規格。
且預期該產物應為可迅速過濾與容易乾燥之型式。另外,經濟上預期為無須特殊保存條件即可在一段延長的時間內為穩定的產物。
但要自從有機溶劑獲得式(I)化合物的結晶型已知為困難。
已發現可以商業規模可重現之方法產生結晶型式(I)化合物的半水合物。
本發明提供式(I)化合物的半水合物結晶型做為新穎的材料,特別是以醫藥上可接受之型式。
本發明之發明人已發現可從含水之溶劑中結晶出式(I)化合物,且該式(I)化合物的半水合物的結晶型具備良好的操作性質與特性。
據此,本發明係關於:1.一種結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物。
2.一種結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物,以粉末X-射線繞射圖譜(powder x-ray diffraction pattern)特徵化,包括使用CuKα
放射線測量之下述2θ值:4.36±0.2、13.54±0.2、16.00±0.2、19.32±0.2及20.80±0.2。
3.一種結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物,其具有與第1圖所示實質上相同之X-射線粉末繞射圖譜。
4.一種結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物,其具有與第2圖所示實質上相同之IR圖譜(infra-red spectrum)。
5.一種用以製備結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之方法,其包括形成1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯之溶液,並利用沈澱或再結晶從該溶液結晶該半水合物。
6.一種醫藥組成物,包括有效量的結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物及醫藥上可接受的載劑。
7.一種用於治療或延緩糖尿病、糖尿病視網膜病變、糖尿病神經病變、糖尿病腎病變、延遲性傷口癒合、胰島素阻抗性、高血糖症、高胰島素血症、脂肪酸的血中濃度升高、甘油的血中濃度升高、高脂血症、肥胖、高三酸甘油酯血症、X症候群(syndrome X)、糖尿病併發症、動脈粥狀硬化症或高血壓之進展或發病之方法,其包括投藥有效量的結晶型1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物。
如所述,本發明包含某些固態結晶型。多種方法可用以特徵化該等型式之存在,且本發明不應被所選擇的方法、或用來特徵化本發明化合物的設備而限制。舉例言之,以X-射線繞射圖譜而言,在實驗圖譜中,該繞射波峰強度可有所變化,如已知於本技術領域,主要起因於所製備樣品的較佳定向(該結晶的非任意定向)。因此,熟習本領域技藝之人士可瞭解,本發明之範疇必須考量到特徵的變異度。
X-射線粉末繞射圖譜本發明(I)之結晶型可藉由其X-射線粉末繞射圖譜而特徵化。該化合物(I)的半水合物的結晶型的X-射線繞射圖譜係以X-射線繞射儀(RINT-TTR,Rigaku,Tokyo,Japan),使用CuKα
放射線測量。X-射線粉末繞射之方法如下:掃瞄率:2.00度/分鐘。目標:CuKα
。電壓:50仟伏特(kV)。電流:300毫安培(mA)。掃瞄範圍:自3至40.0度。取樣寬度:0.0200度。
紅外線圖譜本發明之結晶型在礦物油中的紅外線圖譜包括下列主要波峰:1626、1600、1549、與1507 cm-1
。
結晶型化合物(I)的半水合物的紅外線圖譜,係伴隨以縱軸為透射率(%)且橫軸為波數(cm-1
)之圖式而顯示。
熱重量分析(thermogravimetric analysis)已觀察到本發明之結晶型會以半水合物型式而存在。本發明之結晶型的水含量理論值為1.98%。對於本發明之結晶型的熱重量分析顯示1.705%之重量損失。
熱重量分析之方法如下:秤重約8毫克的化合物(I)半水合物,並移至Tg-50(Shimadzu,Japan)的鋁製樣品槽(cell holder),接著,結晶型化合物(I)半水合物的熱重量(Tg)熱曲線係以5℃/分鐘的加熱速率測得。典型的測量範圍係自常溫至150℃。
本發明亦提供化合物(I)半水合物之結晶型之製備方法,其係包括形成化合物(I)之溶液並自該溶液沈澱出結晶型。
典型地,可自式(I)之化合物、良溶劑及水、視需要含有之不良溶劑的混合物獲得化合物(I)半水合物之結晶型。
有時候,某些雜質會作用為結晶抑制劑,且雜質需以習知方法移除,如矽膠管柱層析。然而,該式(I)化合物半水合物之結晶型甚至可自相對不純的化合物(I)獲得。
本發明亦提供包括結晶型化合物(I)半水合物及醫藥上可接受的載劑的醫藥組成物。
本發明的結晶型化合物具有作為鈉依賴性葡萄糖轉運體抑制劑之活性,並顯示極佳的降血糖效果。
本發明的結晶型預期有用於治療、預防或延緩糖尿病(第1型與第2型糖尿病等)、糖尿病併發症(如糖尿病視網膜病變、糖尿病神經病變、糖尿病腎病變)、餐後高血糖症、延遲性傷口癒合、胰島素阻抗性、高血糖症、高胰島素血症、脂肪酸的血中濃度升高、甘油的血中濃度升高、高脂血症、肥胖、高三酸甘油酯血症、X症候群、動脈粥狀硬化症或高血壓之進展或發病。
本發明的結晶型或其醫藥上可接受的鹽類可以口服或非腸道投藥,並可以適當的醫藥製劑型式而使用。對於口服投藥的適當醫藥製劑包含,舉例言之,固態製劑如錠劑、粒劑、膠囊、及粉末,或液態製劑、懸浮製劑、乳化製劑等。對於非腸道投藥的適當醫藥製劑包含,舉例言之,栓劑;注射製劑或靜脈點滴製劑,利用注射用蒸餾水、生理食鹽水溶液或葡萄糖水溶液;及吸入製劑。
此處的醫藥組成物將於每劑量單位,即錠劑、膠囊、粉末、注射劑、栓劑、一茶匙量(teaspoonful)等,包含有效成分自約0.01毫克/公斤至約100毫克/公斤體重(較佳自約0.01毫克/公斤至約50毫克/公斤;且更佳自約0.01毫克/公斤至約30毫克/公斤),且可給予劑量自約0.01毫克/公斤/天至約100毫克/公斤/天(較佳自約0.01毫克/公斤/天至約50毫克/公斤/天,且更佳自約0.01毫克/公斤/天至約30毫克/公斤/天)。治療描述於本發明之症狀之方法可使用包括如此處定義的結晶型及醫藥上可接受之載體之醫藥組成物而實施。該劑量型將包含活性成分自約0.01毫克/公斤至約100毫克/公斤(較佳自約0.01毫克/公斤至約50毫克/公斤,且更佳自約0.01毫克/公斤至約30毫克/公斤),並可構成適合所選擇的投藥模式之任何型式。然而,該劑量可依投藥途徑、個體之需求、欲治療症狀的嚴重度、及所使用的化合物而不同。可應用於每日投藥或後週期性用藥(post-periodic dosing)之使用。
若需要時,本發明結晶型可與一種或多種之其他抗糖尿病劑、抗高血糖劑、及/或其他疾病治療劑組合使用。本發明化合物與該等其他治療劑可以相同劑型、或分開的口服劑型或注射投藥。
該等治療劑之劑量可依,例如,年齡、體重、病患症狀、投藥途徑、與劑量型式而不同。
該等醫藥組成物可以口服投藥至哺乳類,包含人類、黑猩猩、與狗,以例如錠劑、膠囊、粒劑、或粉末,或非腸道投藥的注射劑型、或鼻內投藥、或皮膚貼布劑型之劑量型式。
可自該化合物(I)、良溶劑與水、視需要含有之溶劑之混合物製備該式(I)化合物半水合物之結晶型。
已發現為適當之良溶劑之實例包含酮類(如丙酮、2-丁酮)、酯類(如乙酸乙酯、乙酸甲酯)、醇類(如甲醇、乙醇、異丙醇),與該等溶劑之混合物。不良溶劑之實例包含烷類(如己烷、庚烷)、芳族烴類(如苯、甲苯)、醚類(如乙醚、二甲基醚、二異丙基醚)與該等溶劑之混合物。
該式(I)化合物之半水合物的結晶型之一較佳製劑,典型地,包括依據專利WO2005/012326冊本所描述之方法所製備之式(I)之粗產物或非晶形化合物溶解於良溶劑中(如酮類或酯類),並加入水及不良溶劑(如烷類或醚類)至該所得溶液,接著過濾。
在可溶於水之良溶劑之情況中,無須使用不良溶劑,且可將水加入該式(I)化合物於良溶劑中之溶液,依此,可降低該式(I)化合物在該溶液中的溶解性。
在使用不良溶劑之情況中,水的較佳用量係對該式(I)化合物為1至10莫耳當量(molar equivalent),良溶劑的較佳用量係為水的容積的10至100倍,且該不良溶劑的較佳用量係為該良溶劑的容積的0.1至10倍。
形成該式(I)化合物之半水合物的結晶型之精確條件可依經驗而決定。
在該等條件下,較佳可於降低的、常溫的、或升高的溫度進行結晶作用。
該式(I)化合物之半水合物之結晶型明顯較非晶型化合物容易單離,且可在冷卻後自該結晶作用之基質過濾、並洗滌與乾燥而得。又,本發明之結晶型較式(I)化合物之非晶型更為穩定。
依描述於專利WO 2005/012326之相似方法製備1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯。
(1)在氬氣氣氛中、於-67至-70℃,將正-丁基鋰(1.6 M己烷溶液,50.0毫升)滴入5-溴-1-[5-(4-氟苯基)-2-噻吩基甲基]-2-甲基苯(1
,28.9克)於四氫呋喃(480毫升)與甲苯(480毫升)之溶液中,且將該混合物於相同溫度攪拌20分鐘。將2
(34.0克)於甲苯(240毫升)之溶液於相同溫度滴入,且將混合物於相同溫度進一步攪拌1小時。接著,將甲基磺酸(21.0克)於甲醇(480毫升)之溶液滴入,並將所得混合物回溫至室溫並攪拌17小時。混合物於冰-水冷卻中放涼,並加入飽和碳酸氫鈉水溶液。混合物以乙酸乙酯萃取,並以濃鹽水洗滌合併的有機層並以硫酸鎂乾燥。濾除不溶物並減壓揮發溶劑。殘餘物以甲苯(100毫升)-己烷(400毫升)磨碎,獲得1-(1-甲氧基吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯(3
)(31.6克)。APCI-Mass m/z 492(M+NH4
)。
(2)在氬氣氣氛中,利用乾冰-丙酮浴冷卻3
(63.1克)與三乙基矽烷(46.4克)在二氯甲烷(660毫升)之溶液,並滴入三氟化硼.乙醚之複合物(50.0毫升),且於相同溫度攪拌混合物。將混合物回溫至0℃並攪拌2小時。於相同溫度下,加入飽和碳酸氫鈉水溶液(800毫升),並攪拌混合物30分鐘。減壓揮發有機溶劑,並將殘餘物注入水中並以乙酸乙酯萃取兩次。有機層以水洗滌兩次,以硫酸鎂乾燥並以活性碳處理。濾除不溶物並減壓揮發溶劑。殘餘物溶解於乙酸乙酯(300毫升),並加入乙醚(600毫升)與H2
O(6毫升)。混合物於室溫攪拌隔夜,並收集沈澱物,以乙酸乙酯-乙醚(1:4)洗滌,並於室溫減壓乾燥以獲得1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物(33.5克)之無色結晶。mp 98-100℃。APCI-Mass m/z 462(M+NH4
)。
1
H-NMR(DMSO-d6
)δ 2.26(3H,s),3.13-3.28(4H,m),3.44(1H,m),3.69(1H,m),3.96(1H,d,J=9.3 Hz),4.10,4.15(each 1H,d,J=16.0 Hz),4.43(1H,t,J=5.8 Hz),4.72(1H,d,J=5.6 Hz),4.92(2H,d,J=4.8 Hz),6.80(1H,d,J=3.5 Hz),7.11-7.15(2H,m),7.18-7.25(3H,m),7.28(1H,d,J=3.5 Hz),7.59(2H,dd,J=8.8,5.4 Hz).Anal.Calcd.for C24
H25
FO5
S.0.5H2
O:C,63.56;H,5.78;F,4.19;S,7.07.Found:C,63.52;H,5.72;F,4.08;S,7.00.
1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯之非晶型粉末(1.62克)溶於丙酮(15毫升),並於其中加入H2
O(30毫升)及晶種。混合物於室溫攪拌18小時,並收集沈澱物,以丙酮-H2
O(1:4,30毫升)洗滌,並在室溫減壓乾燥以獲得1-(β
-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物(1.52克)之無色結晶。mp 97-100℃。
第1圖為式(I)化合物的半水合物的結晶之X-射線粉末繞射圖譜。
第2圖為式(I)化合物的半水合物的結晶之紅外線圖譜。
無元件符號
Claims (7)
- 一種1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之結晶型,其具有包括使用CuKα 放射線測量之下列2θ值之粉末X-射線繞射圖譜:3.84、10.64、10.90、13.02、13.58、13.92、14.24、15.16、15.46、15.60、15.94、16.22、17.30、18.26、18.80、19.10、19.38、20.28、21.08、21.40、21.80、22.50、22.76、23.18、23.40、23.82、24.08、24.48、25.10、25.64、26.28、26.80、27.30、28.56、29.82、30.32、31.16、31.64、32.16、32.58、32.82、33.04、33.30、34.70、35.58、36.42、及39.68(各±0.2)。
- 如申請專利範圍第1項之1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之結晶型,其具有與第1圖所示實質上相同之X-射線繞射圖譜。
- 一種1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之結晶型,其具有在礦物油中的紅外線圖譜包括下列主要波峰:1626、1600、1549、與1507 cm-1 。
- 如申請專利範圍第3項之1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之結晶型,其具有與第2圖所示實質上相同之IR圖譜。
- 一種用以製備申請專利範圍第1至4項中任一項之1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之結晶型之方法,其包括形成1-(β-D- 吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯、良溶劑及水、視需要含有之不良溶劑的混合物,並利用沈澱或再結晶將該半水合物自該混合物結晶,其中,該良溶劑係選自酮類、酯類、醇類,與該等溶劑之混合物之溶劑,及該不良溶劑係選自烷類、芳族烴類、醚類與該等溶劑之混合物之溶劑。
- 一種醫藥組成物,包括有效量之申請範圍第1至4項中任一項之1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之結晶型及醫藥上可接受的載劑。
- 一種申請專利範圍第1至4項中任一項之1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯半水合物之用途,係用於製造用以治療或延緩糖尿病、糖尿病視網膜病變、糖尿病神經病變、糖尿病腎病變、延遲性傷口癒合、胰島素阻抗性、高血糖症、高胰島素血症、脂肪酸的血中濃度升高、甘油的血中濃度升高、高脂血症、肥胖、高三酸甘油酯血症、X症候群、糖尿病併發症、動脈粥狀硬化症或高血壓之進展或發病之藥劑。
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Families Citing this family (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
UY30730A1 (es) * | 2006-12-04 | 2008-07-03 | Mitsubishi Tanabe Pharma Corp | Forma cristalina del hemihidrato de 1-(b (beta)-d-glucopiranosil) -4-metil-3-[5-(4-fluorofenil) -2-tienilmetil]benceno |
KR101552187B1 (ko) * | 2007-09-10 | 2015-09-10 | 얀센 파마슈티카 엔.브이. | Sglt 억제제로서 유용한 화합물의 제조 방법 |
CN102177147A (zh) | 2008-08-22 | 2011-09-07 | 泰拉科斯有限公司 | 制备sglt2抑制剂的方法 |
US9056850B2 (en) * | 2008-10-17 | 2015-06-16 | Janssen Pharmaceutica N.V. | Process for the preparation of compounds useful as inhibitors of SGLT |
CN102307577A (zh) | 2009-02-13 | 2012-01-04 | 贝林格尔.英格海姆国际有限公司 | 包含sglt2抑制剂、dpp-iv抑制剂和任选的另一种抗糖尿病药的药物组合物及其用途 |
US20110009347A1 (en) * | 2009-07-08 | 2011-01-13 | Yin Liang | Combination therapy for the treatment of diabetes |
CA2767258C (en) * | 2009-07-10 | 2016-09-13 | Janssen Pharmaceutica Nv | Crystallisation process for 1-(.beta.-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene |
US8869918B2 (en) | 2009-10-07 | 2014-10-28 | Longyear Tm, Inc. | Core drilling tools with external fluid pathways |
EA024368B1 (ru) * | 2009-10-14 | 2016-09-30 | Янссен Фармацевтика Нв | Процесс получения соединений для применения в качестве ингибиторов sglt2 |
WO2011070592A2 (en) | 2009-12-09 | 2011-06-16 | Panacea Biotec Ltd. | Novel sugar derivatives |
CN102115468B (zh) * | 2009-12-31 | 2014-06-11 | 上海特化医药科技有限公司 | 一种2,5-二取代噻吩化合物的合成方法 |
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
WO2011120923A1 (en) | 2010-03-30 | 2011-10-06 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition comprising an sglt2 inhibitor and a ppar- gamma agonist and uses thereof |
JP6227406B2 (ja) * | 2010-05-11 | 2017-11-08 | ヤンセン ファーマシューティカ エヌ.ベー. | SGLTの阻害剤としての1−(β−D−グルコピラノシル)−2−チエニル−メチルベンゼン誘導体を含有する医薬製剤 |
CN105769792A (zh) | 2010-05-11 | 2016-07-20 | 田边三菱制药株式会社 | 含1-(β-D-吡喃葡糖基)-3-(苯基噻吩基甲基)苯化合物的片剂 |
WO2011153712A1 (en) | 2010-06-12 | 2011-12-15 | Theracos, Inc. | Crystalline form of benzylbenzene sglt2 inhibitor |
EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
US20120009259A1 (en) * | 2010-07-06 | 2012-01-12 | Urbain Alfons Clementina Delaet | Formulation for co-therapy treatment of diabetes |
WO2012041898A1 (en) | 2010-09-29 | 2012-04-05 | Celon Pharma Sp. Z O.O. | Combination of sglt2 inhibitor and a sugar compound for the treatment of diabetes |
US20120283169A1 (en) | 2010-11-08 | 2012-11-08 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
US20130035281A1 (en) | 2011-02-09 | 2013-02-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
CA2832938C (en) * | 2011-04-13 | 2019-09-03 | Janssen Pharmaceutica Nv | Process for the preparation of compounds useful as inhibitors of sglt2 |
US9035044B2 (en) * | 2011-05-09 | 2015-05-19 | Janssen Pharmaceutica Nv | L-proline and citric acid co-crystals of (2S, 3R, 4R, 5S,6R)-2-(3-((5-(4-fluorophenyl)thiopen-2-yl)methyl)4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol |
MX2013014135A (es) | 2011-06-03 | 2014-01-23 | Boehringer Ingelheim Int | Inhibidores de sglt2 para tratar trastornos metabolicos en pacientes tratados con agentes neurolepticos. |
WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
JP2014530186A (ja) | 2011-09-13 | 2014-11-17 | パナセア バイオテック リミテッド | 新規sglt阻害剤 |
EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
CN103889429B (zh) * | 2011-10-31 | 2016-10-19 | 台湾神隆股份有限公司 | Sglt2抑制剂的结晶和非结晶形式 |
US9193751B2 (en) | 2012-04-10 | 2015-11-24 | Theracos, Inc. | Process for the preparation of benzylbenzene SGLT2 inhibitors |
CN103965267A (zh) * | 2013-01-24 | 2014-08-06 | 江苏豪森医药集团连云港宏创医药有限公司 | 1-(β-D-吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯与L-苯丙氨酸共晶物及其制备方法 |
WO2014159151A1 (en) | 2013-03-14 | 2014-10-02 | Msd International Gmbh | Methods for preparing sglt2 inhibitors |
JP2016512817A (ja) | 2013-03-15 | 2016-05-09 | ヤンセン ファーマシューティカ エヌ.ベー. | 高尿酸血症の治療におけるカナグリフロジンとプロベネシドの組合せ |
DK2981269T3 (da) | 2013-04-04 | 2023-10-23 | Boehringer Ingelheim Vetmedica Gmbh | Behandling af stofskifteforstyrrelser hos hestedyr |
CA2911261A1 (en) * | 2013-05-08 | 2014-11-13 | Lek Pharmaceuticals D.D. | Novel crystalline hydrates of 1-(.beta.-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene |
WO2014195966A2 (en) | 2013-05-30 | 2014-12-11 | Cadila Healthcare Limited | Amorphous form of canagliflozin and process for preparing thereof |
WO2015051484A1 (en) | 2013-10-12 | 2015-04-16 | Theracos, Inc. | Preparation of hydroxy-benzylbenzene derivatives |
CN103641822B (zh) * | 2013-10-21 | 2016-06-08 | 江苏奥赛康药业股份有限公司 | 一种卡格列净化合物及其药物组合物 |
CN103588762A (zh) * | 2013-11-27 | 2014-02-19 | 苏州晶云药物科技有限公司 | 坎格列净的新晶型及其制备方法 |
WO2015071761A2 (en) * | 2013-11-11 | 2015-05-21 | Crystal Pharmatech Co., Ltd. | Crystalline forms b, c, and d of canagliflozin |
SI3862003T1 (sl) | 2013-12-17 | 2024-02-29 | Boehringer Ingelheim Vetmedica Gmbh | Inhibitor SGLT-2 za uporabo pri zdravljenju metabolične motnje pri mačjih živalih |
EP3485890B1 (en) * | 2014-01-23 | 2023-05-10 | Boehringer Ingelheim Vetmedica GmbH | Sglt2 inhibitors for treatment of metabolic disorders in canine animals |
EA201691555A1 (ru) * | 2014-01-31 | 2017-01-30 | Янссен Фармацевтика Нв | Способы лечения и предотвращения заболеваний почек и жировых дистрофий печени |
CN105121434B (zh) | 2014-03-19 | 2017-08-29 | 杭州普晒医药科技有限公司 | 坎格列净一水合物及其晶型、它们的制备方法和用途 |
CN103980261B (zh) * | 2014-04-01 | 2016-06-29 | 天津大学 | 卡格列净的a晶型及其结晶制备方法 |
CN103980262B (zh) * | 2014-04-01 | 2016-06-22 | 天津大学 | 卡格列净的b晶型及其结晶制备方法 |
PT3125882T (pt) | 2014-04-01 | 2020-08-17 | Boehringer Ingelheim Vetmedica Gmbh | Tratamento de distúrbios metabólicos em animais equinos |
CN103896930B (zh) * | 2014-04-02 | 2016-08-17 | 安徽联创生物医药股份有限公司 | 卡格列净半水合物药用晶型的制备方法 |
EP2933255A1 (en) | 2014-04-17 | 2015-10-21 | LEK Pharmaceuticals d.d. | Novel crystalline form of 1-(beta-D-glucopyranosyl)-4- methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene |
CN103936726B (zh) * | 2014-04-18 | 2016-06-15 | 王军 | 晶体、制备方法及其用途 |
CN103936800A (zh) * | 2014-05-08 | 2014-07-23 | 安徽联创药物化学有限公司 | 1-(1-甲氧基吡喃葡糖基)-4-甲基-3-[5-(4-氟苯基)-2-噻吩基甲基]苯的制备方法 |
EP2947077A1 (en) | 2014-05-19 | 2015-11-25 | LEK Pharmaceuticals d.d. | Stereoselective synthesis of intermediates in the preparation of ß-C-arylglucosides |
CN105330706B (zh) * | 2014-06-05 | 2019-04-16 | 江苏豪森药业集团有限公司 | 卡格列净中间体的制备方法 |
CN105319294B (zh) * | 2014-06-20 | 2021-03-30 | 重庆医药工业研究院有限责任公司 | 一种分离测定卡格列净及其有关物质的方法 |
CN104761546A (zh) * | 2014-06-21 | 2015-07-08 | 山东富创医药科技有限公司 | 一种新颖的 (1s)-1,5-脱氢-1-[3-[[5-(4-氟苯基)-2-噻吩基]甲基]-4-甲基苯基]-d-葡萄糖醇晶型及其制备方法 |
WO2016016774A1 (en) * | 2014-07-31 | 2016-02-04 | Sun Pharmaceutical Industries Limited | Crystalline forms of canagliflozin |
EP2990029A1 (en) | 2014-08-29 | 2016-03-02 | Sandoz Ag | Pharmaceutical compositions comprising Canagliflozin |
US20170247359A1 (en) | 2014-09-05 | 2017-08-31 | Mylan Laboratories Ltd. | Process for the preparation of canagliflozin |
CZ2014634A3 (cs) | 2014-09-16 | 2016-03-23 | Zentiva, K.S. | Komplexy canagliflozinu a cyklodextrinů |
AU2015320975B2 (en) | 2014-09-25 | 2020-10-08 | Boehringer Ingelheim Vetmedica Gmbh | Combination treatment of SGLT2 inhibitors and dopamine agonists for preventing metabolic disorders in equine animals |
CN104402946B (zh) * | 2014-11-17 | 2018-01-02 | 连云港恒运药业有限公司 | 卡格列净中间体及其无定形的制备方法 |
CN105753910A (zh) * | 2014-12-16 | 2016-07-13 | 康普药业股份有限公司 | 一种卡格列净中间体的制备方法 |
CN104530023A (zh) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | 一种卡格列净晶型i及其制备方法 |
CN104945392A (zh) * | 2015-01-27 | 2015-09-30 | 江苏嘉逸医药有限公司 | 结晶型卡格列净一水合物、制备方法及其应用 |
CN104530024B (zh) * | 2015-02-04 | 2017-08-08 | 上海迪赛诺药业有限公司 | 1‑(β‑D‑吡喃葡糖基)‑4‑甲基‑3‑[5‑(4‑氟苯基)‑2‑噻吩基甲基]苯的晶型及其制备方法 |
JP2018087140A (ja) * | 2015-02-27 | 2018-06-07 | 田辺三菱製薬株式会社 | 1−(β−D−グルコピラノシル)−4−メチル−3−[5−(4−フルオロフェニル)−2−チエニルメチル]ベンゼンの新規結晶 |
EP3262039A4 (en) * | 2015-02-27 | 2018-11-14 | MSN Laboratories Private Limited | Process for the preparation of amorphous (1s)-1,5-anhvdro-1-[3-[[5-(4 fluorophennyl)-2-thienyl]methvl]-4-methylphenyl]-d-glucitol and its polymorphs thereof |
WO2016142950A1 (en) * | 2015-03-11 | 2016-09-15 | Harman Finochem Limited | A novel process for preparing (2s,3r,4r,5s,6r)-2-{3-[5-[4-fluoro-phenyl)- thiophen-2-ylmethyl]-4-methyl-phenyl}-6-hydroxymethyl-tetrahydro-pyran-3,4,5- triol and its stable amorphous hemihydrate form |
WO2016191173A1 (en) * | 2015-05-22 | 2016-12-01 | Janssen Pharmaceutica Nv | Anhydrous crystalline form of (1s)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-d-glucitol |
CN106279134A (zh) * | 2015-06-23 | 2017-01-04 | 中美华世通生物医药科技(武汉)有限公司 | 卡格列净单晶及其制备方法和用途 |
CZ2015435A3 (cs) | 2015-06-25 | 2017-01-04 | Zentiva, K.S. | Pevné formy amorfního canagliflozinu |
US20170071970A1 (en) | 2015-09-15 | 2017-03-16 | Janssen Pharmaceutica Nv | Co-therapy comprising canagliflozin and phentermine for the treatment of obesity and obesity related disorders |
US10428053B2 (en) | 2015-09-15 | 2019-10-01 | Laurus Labs Limited | Co-crystals of SGLT2 inhibitors, process for their preparation and pharmaceutical compositions thereof |
WO2017064679A1 (en) * | 2015-10-15 | 2017-04-20 | Lupin Limited | Process for the preparation of amorphous canagliflozin |
WO2017071813A1 (en) * | 2015-10-30 | 2017-05-04 | Zaklady Farmaceutyczne Polpharma Sa | Process for the preparation of a pharmaceutical agent |
CZ2015824A3 (cs) * | 2015-11-20 | 2017-05-31 | Zentiva, K.S. | Krystalická forma Canagliflozinu a způsob její přípravy |
DK3394051T3 (da) * | 2015-12-21 | 2020-07-20 | Janssen Pharmaceutica Nv | Krystallisationsprocedure til opnåelse af krystaller af canagliflozinhemihydrat |
CN105541818A (zh) * | 2016-03-04 | 2016-05-04 | 浙江华海药业股份有限公司 | 一种卡格列净水合物新晶型及其制备方法 |
CN107540706A (zh) * | 2016-06-28 | 2018-01-05 | 山东诚创医药技术开发有限公司 | 伊格列净中间体的制备方法 |
WO2018020506A1 (en) | 2016-07-25 | 2018-02-01 | Natco Pharma Ltd | Process for the preparation of amorphous form of canagliflozin |
KR20190070956A (ko) | 2016-10-19 | 2019-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | Ssao/vap-1 억제제 및 sglt2 억제제를 포함하는 복합제제 및 이의 용도 |
CN108017626A (zh) * | 2016-11-04 | 2018-05-11 | 上海奥博生物医药技术有限公司 | 一种坎格列净半水合物新晶型 |
CN106588898A (zh) | 2017-02-20 | 2017-04-26 | 浙江华海药业股份有限公司 | 一种卡格列净无定型的制备方法 |
TWI835735B (zh) | 2017-06-12 | 2024-03-21 | 比利時商健生藥品公司 | 減少或預防第ii型糖尿病患者中心血管事件之方法 |
CN109553649B (zh) * | 2017-09-26 | 2020-12-04 | 北大方正集团有限公司 | 一种卡格列净中间体的制备方法 |
WO2019201752A1 (en) | 2018-04-17 | 2019-10-24 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition, methods for treating and uses thereof |
WO2020039394A1 (en) | 2018-08-24 | 2020-02-27 | Novartis Ag | New drug combinations |
TW202103709A (zh) | 2019-03-26 | 2021-02-01 | 比利時商健生藥品公司 | 用於治療患有慢性腎臟病之對象的方法 |
CN114727624A (zh) | 2019-11-28 | 2022-07-08 | 勃林格殷格翰动物保健有限公司 | Sglt-2抑制剂在非人哺乳动物的停奶中的用途 |
CA3167531A1 (en) | 2020-02-17 | 2021-08-26 | Boehringer Ingelheim Vetmedica Gmbh | Use of sglt-2 inhibitors for the prevention and/or treatment of cardiac diseases in felines |
US20230201174A1 (en) | 2020-04-22 | 2023-06-29 | Bayer Aktiengesellschaft | Combination of finerenone and a sglt2 inhibitor for the treatment and/or prevention of cardiovascular and/or renal diseases |
CN113943329A (zh) * | 2020-07-16 | 2022-01-18 | 尚科生物医药(上海)有限公司 | 一种坎格列净中间体的非对映异构体的制备方法 |
EP4206212A4 (en) | 2020-09-30 | 2024-05-22 | Beijing Creatron Institute of Pharmaceutical Research Co., Ltd. | SGLT-2 AND SARCOSINE INHIBITOR COCRYSTAL, PROCESS FOR PREPARATION THEREFOR AND USE THEREOF |
CN117715639A (zh) | 2021-07-28 | 2024-03-15 | 勃林格殷格翰动物保健有限公司 | Sglt-2抑制剂用于预防和/或治疗非人哺乳动物中的肾脏病的用途 |
AU2022319909A1 (en) | 2021-07-28 | 2024-02-22 | Boehringer Ingelheim Vetmedica Gmbh | Use of sglt-2 inhibitors for the prevention and/or treatment of cardiac diseases in non-human mammals excluding felines, in particular canines |
WO2023006745A1 (en) | 2021-07-28 | 2023-02-02 | Boehringer Ingelheim Vetmedica Gmbh | Use of sglt-2 inhibitors for the prevention and/or treatment of hypertension in non-human mammals |
WO2023129595A1 (en) | 2021-12-30 | 2023-07-06 | Newamsterdam Pharma B.V. | Obicetrapib and sglt2 inhibitor combination |
US20230381101A1 (en) | 2022-05-25 | 2023-11-30 | Boehringer Ingelheim Vetmedica Gmbh | Aqueous pharmaceutical compositions comprising sglt-2 inhibitors |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005012326A1 (en) * | 2003-08-01 | 2005-02-10 | Tanabe Seiyaku Co., Ltd. | Novel compounds having inhibitory activity against sodium-dependant transporter |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4160861A (en) | 1977-10-03 | 1979-07-10 | Merck & Co., Inc. | Method for the separation of antibiotic macrolides |
US4584369A (en) | 1981-07-31 | 1986-04-22 | Sloan-Kettering Institute For Cancer Research | Anti-leukemic beta-glycosyl C-nucleosides |
JP2544609B2 (ja) | 1986-10-07 | 1996-10-16 | 和光純薬工業株式会社 | Tcnq錯体 |
JP2786896B2 (ja) | 1988-08-19 | 1998-08-13 | ワーナー―ランバート・コンパニー | 置換されたジヒドロイソキノリノンおよび関連化合物 |
JPH04253974A (ja) | 1991-02-05 | 1992-09-09 | Ishihara Sangyo Kaisha Ltd | スルホニル尿素系化合物、それらの製造方法及びそれらを含有する除草剤 |
US5149838A (en) | 1991-09-20 | 1992-09-22 | Merck & Co., Inc. | Intermediates for substituted azetidinones useful as anti-inflammatory and antidegenerative agents |
GB9208161D0 (en) | 1992-04-14 | 1992-05-27 | Pfizer Ltd | Indoles |
US5334225A (en) | 1992-07-15 | 1994-08-02 | Kao Corporation | Keratinous fiber dye composition containing a 2-substituted amino-5-alkylphenol derivative coupler |
US5731292A (en) | 1992-11-12 | 1998-03-24 | Tanabe Seiyaku Co., Ltd. | Dihydrochalcone derivatives which are hypoglycemic agents |
CA2102591C (en) | 1992-11-12 | 2000-12-26 | Kenji Tsujihara | Hypoglycemic agent |
US6297363B1 (en) | 1993-02-12 | 2001-10-02 | Nomura Co., Ltd. | Glycoside indoles |
US5830873A (en) | 1994-05-11 | 1998-11-03 | Tanabe Seiyaku Co., Ltd. | Propiophenone derivative and a process for preparing the same |
US5780483A (en) | 1995-02-17 | 1998-07-14 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
ATE284690T1 (de) | 1995-10-31 | 2005-01-15 | Lilly Co Eli | Antithrombotische diamine |
JP3059088B2 (ja) | 1995-11-07 | 2000-07-04 | 田辺製薬株式会社 | プロピオフェノン誘導体およびその製法 |
JPH09263549A (ja) | 1996-01-25 | 1997-10-07 | Fujisawa Pharmaceut Co Ltd | ベンゼン誘導体の製造法 |
AU719726B2 (en) | 1996-12-26 | 2000-05-18 | Tanabe Seiyaku Co., Ltd. | Propiophenone derivatives and process for preparing the same |
US6153632A (en) | 1997-02-24 | 2000-11-28 | Rieveley; Robert B. | Method and composition for the treatment of diabetes |
JPH10324632A (ja) | 1997-03-25 | 1998-12-08 | Takeda Chem Ind Ltd | 医薬組成物 |
JP2000034239A (ja) | 1998-07-16 | 2000-02-02 | Asahi Glass Co Ltd | トリフルオロメチル化芳香族化合物の製造方法 |
JP3857429B2 (ja) | 1998-07-17 | 2006-12-13 | ポーラ化成工業株式会社 | 含硫黄抗真菌剤 |
US20020032164A1 (en) | 1998-12-30 | 2002-03-14 | Dale Roderic M. K. | Antimicrobial compounds and methods for their use |
GB9912961D0 (en) | 1999-06-03 | 1999-08-04 | Pfizer Ltd | Metalloprotease 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 |
JP4456768B2 (ja) | 2000-02-02 | 2010-04-28 | 壽製薬株式会社 | C−配糖体を含有する薬剤 |
US6627611B2 (en) | 2000-02-02 | 2003-09-30 | Kotobuki Pharmaceutical Co Ltd | C-glycosides and preparation of thereof as antidiabetic agents |
WO2001064669A1 (en) | 2000-03-03 | 2001-09-07 | Pfizer Products Inc. | Pyrazole ether derivatives as anti-inflammatory/analgesic agents |
SK287183B6 (sk) | 2000-03-17 | 2010-02-08 | Kissei Pharmaceutical Co., Ltd. | Glukopyranozyloxybenzylbenzenový derivát, farmaceutická kompozícia s jeho obsahom, ich použitie a medziprodukt |
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 |
WO2002036602A1 (fr) | 2000-11-02 | 2002-05-10 | Ajinomoto Co., Inc. | Nouveaux derives du pyrazole et remedes au diabete contenant ces derniers |
US6476352B2 (en) | 2000-12-18 | 2002-11-05 | General Electric Company | Laser beam stop sensor and method for automatically detecting the presence of laser beam stop material using a laser beam stop sensor |
AU2002225356B2 (en) | 2000-12-28 | 2008-03-06 | Kissei Pharmaceutical Co., Ltd. | Glucopyranosyloxypyrazole derivatives and use thereof in medicines |
TW593329B (en) | 2001-02-26 | 2004-06-21 | Kissei Pharmaceutical | Glucopyranosyloxypyrazole derivatives and pharmaceutical uses thereof |
CA2438595C (en) | 2001-02-27 | 2011-08-09 | Kissei Pharmaceutical Co., Ltd. | Glucopyranosyloxypyrazole derivatives and medicinal use thereof |
JP4190290B2 (ja) | 2001-03-02 | 2008-12-03 | ユニバーシティー オブ ウエスタン オンタリオ | 放射能標識された化合物のポリマー前駆体、ならびにその作製および使用法 |
US6936590B2 (en) | 2001-03-13 | 2005-08-30 | Bristol Myers Squibb Company | C-aryl glucoside SGLT2 inhibitors and method |
ES2258141T3 (es) | 2001-04-11 | 2006-08-16 | Bristol-Myers Squibb Company | Complejos de aminoacidos de glucosidos c-arilo para el tratamiento de la diabetes y procedimiento. |
CA2445346C (en) | 2001-04-27 | 2010-04-06 | Ajinomoto Co., Inc. | N-substituted pyrazole-o-glycoside derivatives and therapeutic agent for diabetes containing the same |
GB0112122D0 (en) | 2001-05-18 | 2001-07-11 | Lilly Co Eli | Heteroaryloxy 3-substituted propanamines |
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 |
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 |
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 |
US20030087843A1 (en) | 2001-09-05 | 2003-05-08 | Washburn William N. | O-pyrazole glucoside SGLT2 inhibitors and method of use |
WO2003035897A2 (en) | 2001-10-24 | 2003-05-01 | Michael Burton | Enzyme substrates for detecting beta-d-ribofuranosidase activity |
CA2464867C (en) | 2001-11-16 | 2014-01-28 | Cutanix Corporation | Pharmaceutical and cosmetic compositions containing oxy group-bearing aromatic aldehydes |
US6617313B1 (en) | 2002-03-13 | 2003-09-09 | Council Of Scientific And Industrial Research | Glucopyranoside and process of isolation thereof from pterocarpus marsupium pharmaceutical composition containing the same and use thereof |
US6562791B1 (en) | 2002-03-29 | 2003-05-13 | Council Of Scientific And Industrial Research | Glucopyranoside, process for isolation thereof, pharmaceutical composition containing same and use thereof |
KR20040099446A (ko) | 2002-04-18 | 2004-11-26 | 아스트라제네카 아베 | 헤테로시클릭 화합물 |
DE10231370B4 (de) | 2002-07-11 | 2006-04-06 | Sanofi-Aventis Deutschland Gmbh | Thiophenglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
TWI254635B (en) | 2002-08-05 | 2006-05-11 | Yamanouchi Pharma Co Ltd | Azulene derivative and salt thereof |
WO2004014931A1 (ja) | 2002-08-09 | 2004-02-19 | Taisho Pharmaceutical Co., Ltd. | アリール5−チオ−β−D−グルコピラノシド誘導体及びそれを含有する糖尿病治療薬 |
US20040102477A1 (en) | 2002-08-23 | 2004-05-27 | Dr. Reddy's Laboratories Limited | Polymorphic forms of (S)-Repaglinide and the processes for preparation thereof |
AU2003262262A1 (en) | 2002-08-27 | 2004-03-19 | Kissei Pharmaceutical Co., Ltd. | Pyrazole derivatives, medicinal composition containing the same, and medicinal use thereof |
DE10258008B4 (de) | 2002-12-12 | 2006-02-02 | Sanofi-Aventis Deutschland Gmbh | Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
DE10258007B4 (de) | 2002-12-12 | 2006-02-09 | Sanofi-Aventis Deutschland Gmbh | Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel |
CA2512389A1 (en) | 2003-01-03 | 2004-07-29 | Bristol-Myers Squibb Company | Methods of producing c-aryl glucoside sglt2 inhibitors |
PL1980560T3 (pl) | 2003-03-14 | 2011-11-30 | Astellas Pharma Inc | Pochodne C-glikozydowe do leczenia cukrzycy |
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 |
AU2003902263A0 (en) | 2003-05-12 | 2003-05-29 | Fujisawa Pharmaceutical Co., Ltd. | Monosaccharide compounds |
WO2004113359A1 (ja) | 2003-06-20 | 2004-12-29 | Kissei Pharmaceutical Co., Ltd. | 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 |
TW200526678A (en) | 2003-08-01 | 2005-08-16 | Janssen Pharmaceutica Nv | Substituted indole-O-glucosides |
UA86042C2 (en) | 2003-08-01 | 2009-03-25 | Янссен Фармацевтика Н.В. | Substituted indazole-o-glucosides |
RS20060320A (en) | 2003-08-01 | 2008-08-07 | Janssen Pharmaceutica N.V., | Substituted indazole-o-glucosides |
EP1679965A4 (en) | 2003-08-01 | 2009-05-27 | Janssen Pharmaceutica Nv | SUBSTITUTED FUSED HETEROCYCLIC C-GLYCOSIDES |
US7094764B2 (en) | 2003-08-01 | 2006-08-22 | Janssen Pharmaceutica N.V. | Substituted benzimidazole-, Benztriazole-, and benzimidazolone-O-glucosides |
WO2005030127A2 (en) | 2003-09-23 | 2005-04-07 | Merck & Co., Inc. | Novel crystalline form of a phosphoric acid salt of a dipeptidyl peptidase-iv inhibitor |
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. |
US7772191B2 (en) | 2005-05-10 | 2010-08-10 | Boehringer Ingelheim International Gmbh | Processes for preparing of glucopyranosyl-substituted benzyl-benzene derivatives and intermediates therein |
WO2007035198A2 (en) | 2005-07-25 | 2007-03-29 | Merck & Co., Inc. | Dodecylsulfate salt of a dipeptidyl peptidase-iv inhibitor |
WO2007054978A2 (en) | 2005-11-10 | 2007-05-18 | Jubilant Organosys Limited | Process for preparing paroxetine hydrochloride hemihydrate |
EP1842850A1 (en) | 2006-03-23 | 2007-10-10 | Sandoz AG | Rosiglitazone hydrochloride hemihydrate |
UY30730A1 (es) † | 2006-12-04 | 2008-07-03 | Mitsubishi Tanabe Pharma Corp | Forma cristalina del hemihidrato de 1-(b (beta)-d-glucopiranosil) -4-metil-3-[5-(4-fluorofenil) -2-tienilmetil]benceno |
KR101552187B1 (ko) † | 2007-09-10 | 2015-09-10 | 얀센 파마슈티카 엔.브이. | Sglt 억제제로서 유용한 화합물의 제조 방법 |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005012326A1 (en) * | 2003-08-01 | 2005-02-10 | Tanabe Seiyaku Co., Ltd. | Novel compounds having inhibitory activity against sodium-dependant transporter |
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