其它产品项目整合

项目整合的本质是一项集合成方法学、反应工程学与过程分析技术于一体的系统工程。其核心逻辑可以概括为以下几点：源头优选：利用如N-硝胺化学等底层方法学突破，从分子层面颠覆传统高成本、高污染路线。过程强化：依托连续流技术，攻克有机金属试剂应用、光化学反应放大等“不可能”任务，实现高危工艺的本质安全。系统集成：整合“反应-淬灭-分离”全流程，利用微流控与在线分析技术，消除批次间的差异，实现药品制造的连续化与智能化。当前，中间体工艺研发正在经历从“经验驱动”向“数据驱动”的转变。AI辅助路线设计、自动化高通量筛选与连续制造平台的结合，将使得“分子结构与最优工艺路径”之间的映射关系逐渐清晰。未来的竞争优势，将属于那些能够将底层化学创新与先进工程技术进行无缝整合的研发体系。
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其它产品项目整合

Nicardipine CAS Registry Number: 55985-32-5 尼卡地平

CAS Name: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl ester
Percent Composition: C 65.12%, H 6.10%, N 8.76%, O 20.02%
Literature References: Dihydropyridine calcium channel blocker. Prepn: M. Murakami et al., BE 811324; eidem, US 3985758 (1974, 1976 both to Yamanouchi); M. Iwanami et al., Chem. Pharm. Bull. 27, 1426 (1979). Vasodilator profile: T. Takenaka et al., Arzneim.-Forsch. 26, 2172 (1976). Absorption, excretion, metabolism: S. Higuchi et al., Xenobiotica 7, 469 (1977). Clinical pharmacology: T. Seki, T. Takenaka, Int. J. Clin. Pharmacol. Biopharm. 15, 267 (1977). Mechanism of action: K. Satoh et al., Clin. Exp. Pharmacol. Physiol. 7, 249 (1980). Acute toxicity study: Y. Odani, T. Sado, Oyo Yakuri 18, 301 (1979), C.A. 92, 104384u (1980). Symposium: Br. J. Clin. Pharmacol. 20, Suppl. 1, 1S-208S (1985). Clinical synergy with captopril, q.v.: K. A. Conrad et al., Clin. Pharmacol. Ther. 42, 113 (1987). Review of pharmacodynamics, pharmacokinetics and therapeutic efficacy: E. M. Sorkin, S. P. Clissold, Drugs 33, 296-345 (1987).

Isradipine CAS Registry Number: 75695-93-1 伊拉地平

CAS Name: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester
Additional Names: isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxyca...
Literature References: Dihydropyridine calcium channel blocker. Prepn: P. Neumann, DE 2949491; idem, US 4466972 (1980, 1984 both to Sandoz). Prepn of enantiomers: A. Vogel, DE 3320616 (1983 to Sandoz), C.A. 101, 7162s (1984). Comparative study of in vitro effects on human and canine cerebral arteries: E. Müller-Schweinitzer, P. Neumann, J. Cereb. Blood Flow Metab. 3, 354 (1983). Effect on a-adrenoceptor mediated vasoconstriction in rats: K. Jie et al., Arch. Int. Pharmacodyn. 278, 72 (1985). Pharmacokinetics: F. L. S. Tee, J. M. Jaffe, Eur. J. Clin. Pharmacol. 32, 361 (1987). Clinical evaluation in angina and coronary artery disease: C. E. Handler, E. Sowton, ibid. 27, 415 (1984); in hypertension: E. B. Nelson et al., Clin. Pharmacol. Ther. 40, 694 (1986). Comparison of hemodynamic effects of enantiomers: R. P. Hof et al., J. Cardiovasc. Pharmacol. 8, 221 (1986). Series of articles on pharmacology and clinical use: Am. J. Med. 86, 1-146 (1989).

Cilnidipine CAS Registry Number: 132203-70-4 西尼地平

CAS Name: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl (2E)-3-phenyl-2-propenyl ester
Additional Names: (±)-(E)-cinnamyl 2-methoxyethyl 1,4-dihyd...
Literature References: Dihydropyridine calcium channel blocker. Prepn: T. Kutsuma et al., EP 161877; eidem, US 4672068 (1985, 1987 both to Fujirebio). Pharmacology: K. Ikeda et al., Oyo Yakuri 44, 433 (1992). Mechanism of action study: M. Hosono et al., J. Pharmacobio-Dyn. 15, 547 (1992). LC-MS determn in plasma: K. Hatada et al., J. Chromatogr. 583, 116 (1992). Clinical study: M. Ishii, Jpn. Pharmacol. Ther. 21, 59 (1993). Acute toxicity study: S. Wada et al., Yakuri to Chiryo 20, Suppl. 7, S1683 (1992), C.A. 118, 32711 (1992).

Nilvadipine CAS Registry Number: 75530-68-6 尼伐地平

CAS Name: 2-Cyano-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-methyl 5-(1-methylethyl) ester
Additional Names: 5-isopropyl-3-methyl-2-cyano-1,4-dihydro-6-methyl-4-(m-...
Literature References: Dihydropyridine calcium channel blocker. Prepn: Y. Sato, BE 879263; idem, US 4338322 (1980, 1982 both to Fujisawa). Structural studies: A. Miyamae et al., Chem. Pharm. Bull. 34, 3071 (1986). Determn in plasma and urine: Y. Tokuma et al., J. Chromatogr. 415, 156 (1987). Preliminary pharmacokinetics and resolution of enantiomers: eidem, J. Pharm. Sci. 76, 310 (1987). Pharmacokinetics in rabbits: Y. Nezasa et al., Kankyo Igaku Kenkyusho Nenpo 38, 200 (1987), C.A. 107, 89273q (1987). Mode of action: P. A. Molyvdas, N. Sperelakis, J. Cardiovasc. Pharmacol. 8, 449 (1986). Cardiovascular effects: G. J. Gross et al., Gen. Pharmacol. 14, 677 (1983). Clinical evaluation in hypertension: K. Mizuno et al., Res. Commun. Chem. Pathol. Pharmacol. 52, 3 (1986).

Amlodipine CAS Registry Number: 88150-42-9 氨氯地平

CAS Name: 2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester
Additional Names: (±)-2-[(2-aminoethoxy)methyl]-4-(2-chloro...
Literature References: Dihydropyridine calcium channel blocker; activity resides mainly in the (-)-isomer. Prepn: S. F. Campbell et al., EP 89167; eidem, US 4572909 (1983, 1986 both to Pfizer). Synthesis and pharmacology of racemate and enantiomers: J. E. Arrowsmith et al., J. Med. Chem. 29, 1696 (1986). Calcium antagonist activity: R. A. Burges et al., J. Cardiovasc. Pharmacol. 9, 110 (1987). GC determn in plasma: A. P. Beresford et al., J. Chromatogr. 420, 178 (1987). Metabolism: idem et al., Xenobiotica 18, 245 (1988). Review of pharmacology and therapeutic efficacy: M. Haria, A. J. Wagstaff, Drugs 50, 560-586 (1995). Clinical potential in severe heart failure: M. Packer et al., N. Engl. J. Med. 335, 1107 (1996). Review of mechanism of plaque stabilization: R. P. Mason, Atherosclerosis 165, 191-199 (2002); of clinical potential in combination with atorvastatin in atherosclerosis: J. W. Jukema, J. W. A. van der Hoorn, Expert Opin. Pharmacother. 5, 459-468 (2004).

Azelnidipine CAS Registry Number: 123524-52-7 阿折地平

CAS Name: 2-Amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-[1-(diphenylmethyl)-3-azetidinyl] 5-(1-methylethyl) ester
Additional Names: (±)-3-(1-diphenylmethyl...
Literature References: Dihydropyridine L-type calcium channel blocker. Prepn: H. Koike et al., EP 266922; eidem, US 4772596 (both 1988 to Sankyo); T. Kobayashi et al., Chem. Pharm. Bull. 43, 797 (1995). Clinical evaluation in hypertension: M. Arita et al., J. Cardiovasc. Pharmacol. 33, 186 (1999). Review of pharmacology: Y. Yagil, A. Lustig, Cardiovasc. Drug Rev. 13, 137-148 (1995); of development, pharmacokinetics, safety, and clinical experience: H. Koike et al., Annu. Rep. Sankyo Res. Lab. 54, 1-64 (2002); of pharmacology and clinical experience: K. Wellington, L. J. Scott, Drugs 63, 2613-2621 (2003).

Lunularic Acid CAS Registry Number: 23255-59-6 半月苔酸

CAS Name: 2-Hydroxy-6-[2-(4-hydroxyphenyl)ethyl]benzoic acid
Additional Names: 6-(p-hydroxyphenethyl)salicylic acid
Percent Composition: C 69.76%, H 5.46%, O 24.78%
Literature References: Dihydrostilbene growth inhibitor isolated from liverworts and algae. Isoln from Lunularia cruciata (L.) Dum., Lunulariaceae, and characterization: I. F. M. Valio et al., Nature 223, 1178 (1969); I. F. M. Valio, W. W. Schwab, J. Exp. Bot. 21, 138 (1970); from more than 70 species of liverwort: J. Gorham, Phytochemistry 16, 249 (1977); from cultures of Marchantia polymorphia: S. Abe, Y. Ohta, ibid. 22, 1917 (1983). Synthesis: Y. Arai et al., Tetrahedron Lett. 1972, 1615; S. Haneck, K. Schreiber, DD 126866 (1977 to Akad. Wissenschaft. D.D.R.), C.A. 88, 152249t (1978). Effect on liverwort growth: J. Gorham, Phytochemistry 17, 99 (1978). Metabolism by L. cruciata: R. J. Pryce, ibid. 11, 1355 (1972).

Olsalazine CAS Registry Number: 15722-48-2 奥沙拉嗪

CAS Name: 3,3'-Azobis(6-hydroxybenzoic acid)
Additional Names: C.I. Mordant Yellow 5; 3,3'-dicarboxy-4,4'-dihydroxyazobenzene; 5,5'-azobis(salicylic acid); azodisal
Percent Composition: C 55...
Literature References: Dimer of mesalamine, q.v., originally used as a mordant dye. Prepn: DE 278613; C. Mettler, US 1157169 (1914, 1915 both to J. R. Geigy). Improved prepn: K. H. Agback, A. S. Nygren, EP 36636; eidem, US 4528367 (1981, 1985 both to Pharmacia AB). HPLC determn in biological samples: R. A. van Hogezand et al., J. Chromatogr. 305, 470 (1984). In vitro effect on fecal bacteria: H. Sandberg-Gertzen et al., Scand. J. Gastroenterol. 20, 607 (1985). Clinical pharmacokinetics and metabolism: C. P. Willoughby et al., Gut 23, 1081 (1982). Clinical trial in ulcerative colitis: H. Sandberg-Gertzen et al., Gastroenterology 90, 1024 (1986). Review of clinical experience in inflammatory bowel disease: A. N. Wadworth, A. Fitton, Drugs 41, 647-664 (1991).

Dosmalfate CAS Registry Number: 122312-55-4 多司马酯

CAS Name: [m7-[7-[[6-O-[6-Deoxy-2,3,4-tri-O-(sulfo-kO)-a-L-mannopyranosyl]-2,3,4-tri-O-(sulfo-kO)-b-D-glucopyranosyl]oxy]-5-hydroxy-2-[4-methoxy-3-[(sulfo-kO)oxy]pheny]-4H-1-benzopyran-4-onato(7-)...
Literature References: Diosmin, q.v., heptakis (hydrogen sulfate) aluminum complex. Prepn: A. Orjales-Venero, R. Mosquera-Pestana, EP 558435; eidem, US 5296469 (1993, 1994 both to FAES). In vivo protective effect in exptl colitis: I. Villegas et al., Eur. J. Pharmacol. 460, 209 (2003). Series of articles on pharmacology, toxicity and clinical studies as gastroprotectant and antiulcerative: Drugs Today 36 (Suppl. A), 25-85 (2000).

Ubenimex CAS Registry Number: 58970-76-6 乌苯美司

CAS Name: N-[(2S,3R)-3-Amino-2-hydroxy-1-oxo-4-phenylbutyl]-L-leucineTrademarks: Bestatin (Nippon Kayaku)
Percent Composition: C 62.32%, H 7.84%, N 9.08%, O 20.75%
Literature References: Dipeptide antitumor antibiotic produced by Streptomyces olivoreticuli with immunostimulant activity; inhibits leucine aminopeptidase and aminopeptidases B and N. Prepn from fermentation broth: H. Umezawa et al., DE 2528984; eidem, US 4052449 (1976, 1977 both to Microbiochem. Res. Found., Japan); eidem, J. Antibiot. 29, 97 (1976). Structure: H. Suda et al., ibid. 100. Synthesis of stereoisomers and structure-activity study: R. Nishizawa et al., J. Med. Chem. 20, 510 (1977). Stereocontrolled synthesis: S. Kobayashi et al., Tetrahedron Lett. 25, 5079 (1984). Crystal structure: J. S. Ricci, Jr. et al., J. Org. Chem. 47, 3063 (1982). Cell surface binding studies: H. Umezawa et al., J. Antibiot. 29, 857 (1976); W. E. Müller et al., Int. J. Immunopharmacol. 4, 393 (1982). Acute toxicity: T. Sakakibara et al., Jpn. J. Antibiot. 36, 2971 (1983). Review of pharmacology: G. Mathé, Biomed. Pharmacother. 45, 49-54 (1991); of clinical studies: K. Ota, ibid. 55-60. Clinical trial in squamous-cell lung carcinoma: Y. Ichinose et al., J. Natl. Cancer Inst. 95, 605 (2003).