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

Vorinostat CAS Registry Number: 149647-78-9 伏立诺他

CAS Name: N-Hydroxy-N'-phenyloctanediamide
Additional Names: suberoylanilide hydroxamic acid; SAHA
Percent Composition: C 63.62%, H 7.63%, N 10.60%, O 18.16%
Literature References: Second generation hybrid polar compound; histone deacetylase (HDAC) inhibitor that induces cell cycle arrest, differentiation and apoptosis in tumor cells. Prepn: R. Breslow et al., WO 9307148; eidem, US 5369108 (1993, 1994 both to Sloan-Kettering Inst.; Columbia Univ.); J. C. Stowell et al., J. Med. Chem. 38, 1411 (1995). Synthesis: A. Mai et al., Org. Prep. Proceed. Int. 33, 391 (2001). HTLC determn in serum: L. Du et al., Rapid Commun. Mass Spectrom. 19, 1779 (2005). In vitro antiproliferative activity: P. N. Munster et al., Cancer Res. 61, 8492 (2001). In vivo antineoplastic activity: L. A. Cohen et al., Anticancer Res. 22, 1497 (2002). Clinical pharmacokinetics and activity in cancer patients: W. K. Kelly et al., J. Clin. Oncol. 23, 3923 (2005). Review of mechanism of action: V. M. Richon et al., Blood Cells Mol. Dis. 27, 260-264 (2001); of development and therapeutic potential: R. W. Johnstone, IDrugs 7, 674-682 (2004).

Actimid (Celgene) CAS Registry Number: 19171-19-8 泊马度胺

CAS Name: 4-Amino-2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione
Additional Names: 3-amino-N-(2,6-dioxo-3-piperidyl)phthalamide; 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline...
Literature References: Second generation immunomodulator and TNF-a inhibitor; analog of thalidomide, q.v. Prepn: G. W. Muller et al., WO 9803502; eidem, US 6335349 (1998, 2002 both to Celgene); eidem, Bioorg. Med. Chem. Lett. 9, 1625 (1999). In vivo immunostimulant activity in cancer vaccine model: K. Dredge et al., J. Immunol. 168, 4914 (2002). Mechanism of action study: F. Payvandi et al., Cell. Immunol. 230, 81 (2004). In vitro immunodulation of hematopoietic stem cells: K.-R. Koh et al., Blood 105, 3833 (2005). Clinical pharmacokinetics and clinical evaluation in multiple myeloma: S. A. Schey et al., J. Clin. Oncol. 22, 3269 (2004).

Clofarabine CAS Registry Number: 123318-82-1 克罗拉滨

CAS Name: 2-Chloro-9-(2-deoxy-2-fluoro-b-D-arabinofuranosyl)-9H-purin-6-amine
Additional Names: 2-chloro-9-(2-deoxy-2-fluoro-b-D-arabinofuranosyl)adenine; 2-chloro-2'-arabinofluoro-2'-deoxyaden...
Literature References: Second generation purine nucleoside analog; antimetabolite that inhibits DNA synthesis and resists deamination by adenosine deaminase. Prepn: K. A. Watanabe et al., EP 219829; eidem, US 4918179 (1987, 1990 both to Sloan-Kettering Inst. Cancer Res.); J. A. Montgomery et al., J. Med. Chem. 35, 397 (1992). Improved synthesis: W. E. Bauta et al., Org. Process Res. Dev. 8, 889 (2004). Antineoplastic activity: W. R. Waud et al., Nucleosides Nucleotides Nucleic Acids 19, 447 (2000). Clinical pharmacology: H. M. Kantarjian et al,. J. Clin. Oncol. 21, 1167 (2003). Clinical pharmacokinetics: V. Gandhi et al., Clin. Cancer Res. 9, 6335 (2003). Clinical evaluation in acute leukemia: H. Kantarjian et al., Blood 102, 2379 (2003); in pediatric patients: S. Jeha et al., ibid. 103, 784 (2004). Review of development: A. Sternberg, Curr. Opin. Invest. Drugs 4, 1479-1487 (2003); of mechanism of action and clinical experience: S. Faderl et al., Cancer 103, 1985-1995 (2005).

Glyburide CAS Registry Number: 10238-21-8 格列苯脲

CAS Name: 5-Chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide
Additional Names: 1-[[p-[2-(5-chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea;...
Literature References: Second generation sulfonylurea with hypoglycemic activity. Prepn: Aumuller et al., Arzneim.-Forsch. 16, 1640 (1966); NL 6603398 (1966 to Boehringer, Mann.), C.A. 66, 65289h (1967); NL 6610580; H. Weber et al., US 3454635 (1967, 1969 both to Hoechst). Pharmacology: Loubatières, Mariani, C.R. Seances Acad. Sci. Ser. D 265, 643 (1967). Toxicity: Mizukami et al., Arzneim.-Forsch. 19, 1413 (1969). Series of articles on synthesis, pharmacology, toxicology and clinical studies: ibid. 1323-1494. Effect on release of insulin, glucagon and somatostatin: S. Efendic et al., Proc. Natl. Acad. Sci. USA 76, 5901 (1979). Symposium on pharmacology, mechanism of action and clinical trials: Ann. Clin. Res. 15, Suppl. 37, 1-35 (1983). Comprehensive description: P. G. Takla, Anal. Profiles Drug Subs. 10, 337-355 (1981). Review of pharmacology and clinical efficacy: J. M. Feldman, Pharmacotherapy 5, 43-62 (1985).

Glipizide CAS Registry Number: 29094-61-9 格列吡嗪

CAS Name: N-[2-[4-[[[(Cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-5-methylpyrazinecarboxamide
Additional Names: 1-cyclohexyl-3-[[p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfony...
Literature References: Second generation sulfonylurea with hypoglycemic activity. Prepn: V. Ambrogi, W. Logemann, DE 2012138; eidem, US 3669966 (1970, 1972 both to Carlo Erba); Ambrogi et al., Arzneim.-Forsch. 21, 200 (1971). Pharmacology: eidem, ibid. 208; Marigo et al., ibid. 215. Metabolism: Goldaniga et al., ibid. 23, 242 (1973); Fuccella et al., J. Clin. Pharmacol. 13, 68 (1973). Toxicity: Ambrogi et al., Arzneim.-Forsch. 21, 208 (1971). Review of pharmacology and therapeutic efficacy: R. N. Brogden et al., Drugs 18, 329-353 (1979); H. E. Lebovitz, Pharmacotherapy 5, 63-77 (1985).

Temoporfin CAS Registry Number: 122341-38-2 替莫卟吩

CAS Name: 3,3',3'',3'''-(2,3-Dihydro-21H,23H-porphine-5,10,15,20-tetrayl)tetrakisphenol
Additional Names: 2,3-dihydro-5,10,15,20-tetra(m-hydroxyphenyl)porphyrin; 5,10,15,20-tetra(m-hydroxypheny...
Literature References: Second generation systemic photosensitizing agent. Prepn: R. Bonnett, M. C. Berenbaum, EP 337601; eidem, US 4992257 (1989, 1991 both to Efamol Holdings); R. Bonnett et al., Biochem. J. 261, 277 (1989). NMR study: idem et al., J. Chem. Soc. Perkin Trans. 2 1994, 1839. Toxicology study: R. B. Veenhuizen et al., Int. J. Cancer 59, 830 (1994). HPLC determn in plasma and tissue: M. Barberi-Heyob et al., J. Chromatogr. B 688, 331 (1997). Clinical pharmacokinetics: T. Glanzmann et al., Photochem. Photobiol. 67, 596 (1998). Clinical evaluation in photodynamic therapy of malignancies: J.-F. Savary et al., Arch. Otolaryngol. Head Neck Surg. 123, 162 (1997).

Minocycline CAS Registry Number: 10118-90-8 米诺环素

CAS Name: [4S-(4a,4aa,5aa,12aa)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide
Additional Names: 7-dimethylamino-6-demethyl-...
Literature References: Second generation tetracycline antibiotic. Prepn: J. Petisi, J. H. Boothe, US 3226436 (1965 to Am. Cyanamid); M. J. Martell, J. H. Boothe, J. Med. Chem. 10, 44 (1967); R. F. R. Church et al., J. Org. Chem. 36, 723 (1971). HPLC determn in tissue and serum: W. R. Wrightson et al., J. Chromatogr. B 706, 358 (1998). Comprehensive description: V. Zbinovsky, G. P. Chrekian, Anal. Profiles Drug Subs. 6, 323-339 (1977). Series of articles on toxicology and metabolism: Toxicol. Appl. Pharmacol. 11, 128-183 (1967). Review of antibacterial activity and pharmacology: M. Jonas, B. A. Cunha, Ther. Drug Monit. 4, 137-145 (1982); of clinical safety and efficacy in acne: K. Freeman, Br. J. Clin. Pract. 43, 112-115 (1989). Clinical evaluation in periodontal disease: R. J. Oringer et al., J. Periodontol. 73, 835 (2002).

Diisopropanolamine CAS Registry Number: 110-97-4 二异丙醇胺

CAS Name: 1,1'-Iminobis-2-propanol
Additional Names: bis(2-hydroxypropyl)amine; DIPA
Percent Composition: C 54.11%, H 11.35%, N 10.52%, O 24.02%
Literature References: Secondary alkanolamine. Prepn: J. N. Wickert, US 1988225 (1935 to Carbide Carbon Chem.). Densities, viscosities, diffusivities: H. Hikita et al., J. Chem. Eng. Jpn. 14, 411 (1981). Absorption and mass transfer study: P. M. M. Blauwhoff, W. P. M. Van Swaaij, ACS Symp. Ser. 196, 377 (1982). Safety assessment and use: K. H. Beyer et al., J. Am. Coll. Toxicol. 6, 53 (1987). Review of use in 'Sulfinol' process: K. E. Zarker, Fert. Sci. Technol. Ser. 2, 219-232 (1974); in gas purification: K. F. Butwell et al., Hydrocarbon Process. Int. Ed. 61, 109-116 (1982).

Digitoxin CAS Registry Number: 71-63-6 洋地黄毒苷

CAS Name: (3b,5b)-3-[(O-2,6-Dideoxy-b-D-ribo-hexopyranosyl-(1®4)-O-2,6-dideoxy-b-D-ribo-hexopyranosyl-(1®4)-2,6-dideoxy-b-D-ribo-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide
Additional Name...
Literature References: Secondary glycoside from Digitalis purpurea L., Scrophulariaceae. Extracted from the dried leaves with 50% alc. Extraction procedure: Cloetta, Arch. Exp. Pathol. Pharmakol. 112, 261 (1926). Purification: Windaus, Freese, Ber. 58, 2503 (1925). Ten kilo leaves yield about 6 grams pure digitoxin. Identity with digitophyllin: Cloetta, Arch. Exp. Pathol. Pharmakol. 88, 113 (1920). Structure: See reviews by Elderfield in Chem. Rev. 17, 187 (1935), and Stoll, The Cardiac Glycosides (London, 1937); also Shoppee in Annu. Rev. Biochem. 11, 103 (1942). Acid hydrolysis yields 1 mol digitoxigenin + 3 mol digitoxose. The sugar residue is attached to the hydroxyl group at C-3 of the aglycon. Structure of the sugar moiety: Lichti et al., Helv. Chim. Acta 45, 868 (1962). Digitoxin U.S.P. is either pure digitoxin or a mixture of cardioactive glycosides obtained from Digitalis purpurea and consisting chiefly of digitoxin. The potency of digitoxin U.S.P. corresp to the potency of an equal wt of U.S.P. Digitoxin Reference Standard. A deviation of 20% is permitted. The physical characteristics given below are those of the pure compd. Toxicity data: Foerster et al., Arch. Int. Pharmacodyn. Ther. 159, 1 (1966). Comprehensive description: I. M. Jakovljevic, Anal. Profiles Drug Subs. 3, 149-172 (1974).

Gitoxin CAS Registry Number: 4562-36-1 格列苯脲杂质A

CAS Name: (3b,5b,16b)-3-[(O-2,6-Dideoxy-b-D-ribo-hexopyranosyl-(1®4)-O-2,6-dideoxy-b-D-ribo-hexopyranosyl-(1®4)-2,6-dideoxy-b-D-ribo-hexopyranosyl)oxy]-14,16-dihydroxycard-20(22)-enolide
Additi...
Literature References: Secondary glycoside mainly from Digitalis purpurea L., also from D. lanata Ehrh., Scrophulariaceae. Byproduct of digitoxin manuf. Isoln: Kraft, Arch. Pharm. 250, 118 (1912); Cloetta, Arch. Exp. Pathol. Pharmakol. 112, 261 (1926); Smith, J. Chem. Soc. 1931, 23. Purification: McChesney et al., J. Am. Pharm. Assoc. 37, 364 (1948). Acid hydrolysis yields 1 mol gitoxigenin + 3 mols digitoxose, q.q.v.: Windaus, Schwarte, Ber. 58, 1515 (1925). See also Satoh, Aoyama, Chem. Pharm. Bull. 18, 94 (1970). Pharmacokinetics in humans: M. Lesne, Int. J. Clin. Pharmacol. Biopharm. 16, 456 (1978). Prepn of pentaacetate: BE 668116; NL 6506250 (1965, 1966 both to VEB Arzneimittelwerk Dresden), C.A. 65, 23366 (1966); 67, 91092d (1967). Toxicity study: Foerster et al., Arch. Int. Pharmacodyn. 155, 165 (1965). Review: R. Megges et al., Pharmazie 32, 665-667 (1977).