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

Gabexate CAS Registry Number: 39492-01-8 甲磺酸加贝酯

CAS Name: 4-[[6-[(Aminoiminomethyl)amino]-1-oxohexyl]oxy]benzoic acid ethyl ester
Additional Names: p-hydroxybenzoic acid ethyl ester 6-guanidinohexanoate; p-carbethoxyphenyl e-guanidinocaproat...
Literature References: Non-peptide proteolytic enzyme inhibitor which also inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, trypsin but not chymotrypsin; cf. aprotinin. Prepn as the p-toluenesulfonate salt: S. Fujii, T. Watanabe, DE 2050484; eidem, US 3751447 (1971, 1973 both to Ono). Enzyme inhibition: M. Muramatu, S. Fujii, Biochim. Biophys. Acta 268, 221 (1972); S. Tamura et al., ibid. 484, 417 (1977). Pharmacology: T. Okegada et al., Nippon Yakurigaku Zasshi 71, 71 (1975), C.A. 84, 218m (1976). Metabolism: M. Sugiyama et al., Oyo Yakuri 9, 733 (1975), C.A. 83, 188145s (1975). Metabolism of inhibitory effect on platelet aggregation: G. Kosaki et al., Thromb. Res. 20, 587 (1980). Beneficial action in traumatic shock: A. M. Lefer et al., IRCS Med. Sci. Libr. Compend. 8, 278 (1980); in exptl acute pancreatitis: J. R. Wisner et al., Pancreas 2, 181 (1987). Comparative clinical study in acute pancreatitis: N. Tanaka et al., Adv. Exp. Med. Biol. 120, 367 (1979). Teratology and toxicity study: T. Fujita et al., Oyo Yakuri 9, 743 (1975), C.A. 83, 188322x (1975).

Clazosentan CAS Registry Number: 180384-56-9 N-(2-(2-(1H-四唑-5-基)吡啶-4-基)-6-(2-羟基乙氧基)-5-(2-甲氧基苯氧基)嘧啶-4-基)-5-甲基吡啶-2-磺酰胺

CAS Name: N-[6-(2-Hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(1H-tetrazol-5-yl)-4-pyridinyl]-4-pyrimidinyl]-5-methyl-2-pyridinesulfonamide
Additional Names: 5-methylpyridine-2-sulfonic acid 6-(2-...
Literature References: Nonpeptide selective endothelin ETA receptor antagonist. Prepn: V. Breu et al., WO 9619459; eidem, US 6004965 (1996, 1999 both to Hoffmann-La Roche). Pharmacology and receptor binding study: S. Roux et al., J. Pharmacol. Exp. Ther. 283, 1110 (1997). Clinical pharmacology: T. J. L. Vuurmans et al., Hypertension 41, 1253 (2003). Cerebrovascular characterization: H. Vatter et al., J. Neurosurg. 102, 1101, 1108 (2005). Clinical effect on vasospasm following subarachnoid hemorrhage: P. Vajkoczy et al., ibid. 103, 9 (2005). Review of development and therapeutic potential: D. Uhlmann, Curr. Opin. Invest. Drugs 7, 272-281 (2006).

Sepimostat CAS Registry Number: 103926-64-3 司匹司他

CAS Name: 4-[(4,5-Dihydro-1H-imidazol-2-yl)amino]benzoic acid 6-(aminoiminomethyl)-2-naphthalenyl ester
Additional Names: 6-amidino-2-naphthyl p-(2-imidazolin-2-ylamino)benzoate
Percent Comp...
Literature References: Nonpeptide serine protease inhibitor; structural analog of nafamostat. Prepn: S. Fujii et al., WO 8600893; eidem, US 4777182 (1986, 1988 both to Torii); T. Nakayama et al., Chem. Pharm. Bull. 41, 117 (1993). Enzyme inhibitory activity: M. Oda et al., Jpn. J. Pharmacol. 52, 23 (1990). Effects on exptl pancreatitis: H. Murakami et al., Arzneim.-Forsch. 40, 1352 (1990). HPLC determn in biological fluids: T. Marunaka et al., J. Chromatogr. 433, 177 (1988). Toxicity study: K. Terazawa et al., J. Toxicol. Sci. 17, Suppl. 4, 1 (1992).

Dabigatran CAS Registry Number: 211914-51-1 达比加群

CAS Name: N-[[2-[[[4-(Aminoiminomethyl)phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-b-alanine
Additional Names: 3-[[2-[(4-carbamimidoylphenylamino)methyl]-1-methyl...
Literature References: Nonpeptide, direct thrombin inhibitor. Prepn and crystal structure of complex with thrombin: N. Hauel et al., WO 9837075; eidem, US 6087380 (1998, 2000 both to Boehringer, Ing.); eidem, J. Med. Chem. 45, 1757 (2002). Review of pharmacology: D. Mungall, Curr. Opin. Invest. Drugs 3, 905-907 (2002). Clinical pharmacokinetics: J. Stangier et al., J. Clin. Pharmacol. 45, 555 (2005). Clinical evaluations in joint replacement: B. I. Eriksson et al., J. Thromb. Haemostas. 2, 1573 (2004); idem et al., ibid. 3, 103 (2005).

Conivaptan CAS Registry Number: 210101-16-9 考尼伐坦

CAS Name: N-[4-[(4,5-Dihydro-2-methylimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide
Additional Names: 4'-[(2-methyl-1,4,5,6-tetrahydro-imidazo[4,5-d][1]benza...
Literature References: Nonpeptide, dual vasopressin V1a/V2 receptor antagonist. Prepn: A. Tanaka et al., WO 9503305; eidem, US 5723606 (1995, 1998 both to Yamanouchi); A. Matsuhisa et al., Chem. Pharm. Bull. 48, 21 (2000). Pharmacology: Y. Yatsu et al., Eur. J. Pharmacol. 321, 225 (1997). Binding specificity study: A. Tahara et al., Peptides 19, 691 (1998). Clinical pharmacokinetics: M. Burnier et al., Eur. J. Clin. Pharmacol. 55, 633 (1999). Clinical evaluation in advanced heart failure: J. E. Udelson et al., Circulation 104, 2417 (2001). Review of clinical development: S. A. Doggrell, Curr. Opin. Invest. Drugs 6, 317-326 (2005).

Tipranavir CAS Registry Number: 174484-41-4 替拉那韦

CAS Name: N-[3-[(1R)-1-[(6R)-5,6-Dihydro-4-hydroxy-2-oxo-6-(2-phenylethyl)-6-propyl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2-pyridinesulfonamide
Additional Names: 5-trifluoromethyl-N-...
Literature References: Nonpeptidic HIV protease inhibitor (NPPI). Prepn: K. R. Romines et al., WO 9530670 (1995 to Upjohn); eidem, US 5852195 (1998 to Pharmacia Upjohn); S. R. Turner et al., J. Med. Chem. 41, 3467 (1998); K. S. Fors et al., J. Org. Chem. 63, 7348 (1998). Antiviral activity: S. M. Poppe et al., Antimicrob. Agents Chemother. 41, 1058 (1997); vs multidrug resistant clinical isolates: B. A. Larder et al., AIDS 14, 1943 (2000). HPLC determn in plasma: E. Dailly et al., J. Chromatogr. B 832, 317 (2006). Clinical pharmacokinetics in combination with ritonavir: T. R. MacGregor et al., HIV Clin. Trials 5, 371 (2004). Clinical evaluation in HIV infection: S. McCallister et al., J. Acquir. Immune Defic. Syndr. 35, 376 (2004). Review of pharmacologic interactions with other HIV medications: M. Boffito et al., J. Clin. Pharmacol. 46, 130-139 (2006); of clinical development: B. Best, R. Haubrich, Expert Opin. Invest. Drugs 15, 59-70 (2006).

g -Aminobutyric Acid CAS Registry Number: 56-12-2 4-氨基丁酸

CAS Name: 4-Aminobutanoic acid
Additional Names: g-amino-n-butyric acid; piperidic acid; GABA
Trademarks: Gammalon (Daiichi)
Percent Composition: C 46.59%, H 8.80%, N 13.58%, O 31.03%
Literature References: Nonprotein amino acid that functions as a neurotransmitter. Prepn from succinimide: Tafel, Stern, Ber. 33, 2224 (1900); from piperylurethan and fuming nitric acid: Schotten, Ber. 16, 643 (1883); Abderhalden, Chem. Zentralbl. 1926, II, 779; from N-(b-bromoethyl)phthalimide and sodiomalonic ester: Aschan, Ber. 24, 2450 (1891); from g-chlorobutyronitrile and potassium phthalimide: Gabriel, Ber. 22, 3335 (1889); 23, 1771 (1890); DeWitt, Org. Synth. coll. vol. II, 25 (1943). Review of biochemical pharmacology: R. Tapia in Handbook of Psychopharmacology, L. L. Iversen et al., Eds. (Plenum, New York, 1975) pp 1-58; L. L. Iversen in Psychopharmacology: A Generation of Progress, M. A. Lipton et al., Eds. (Raven, New York, 1978) pp 25-38; C. C. Mao, E. Costa, ibid. pp 307-318.

Ebastine CAS Registry Number: 90729-43-4 依巴斯汀

CAS Name: 1-[4-(1,1-Dimethylethyl)phenyl]-4-[4-(diphenylmethoxy)-1-piperidinyl]-1-butanone
Additional Names: 4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyrophenone; 4-diphenylmethoxy-1-[3...
Literature References: Nonsedating type histamine H1-receptor antagonist. Prepn: J. M. P. Soto et al., EP 134124; eidem, US 4550116 (both 1985 to Fordonal). Metabolized in vivo to carebastine, its active carboxylic acid metabolite. Clinical pharmacology, pharmacokinetics: J. Vincent et al., Br. J. Clin. Pharmacol. 26, 497 (1988). Effect on psychomotor performance: J. Vincent et al., ibid. 503.

Acrivastine CAS Registry Number: 87848-99-5 阿伐斯汀

CAS Name: (2E)-3-[6-[(1E)-1-(4-Methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]-2-pyridinyl]-2-propenoic acid
Additional Names: (E)-6-[(E)-3-(1-pyrrolidinyl)-1-p-tolylpropenyl]-2-pyridineacrylic ac...
Literature References: Nonsedating type histamine H1-receptor antagonist; analog of triprolidine, q.v. Prepn: G. G. Coker, J. W. A. Findlay, EP 85959 (1983 to Wellcome); J. W. A. Findlay, G. G. Coker, US 4501893 (1985). Pharmacodynamics and pharmacokinetics in humans: A. F. Cohen et al., Eur. J. Clin. Pharmacol. 28, 197 (1985). Evaluation of CNS effects: A. F. Cohen et al., Clin. Pharmacol. Ther. 38, 381 (1985). Clinical trials in idiopathic urticaria: J. G. Gibson et al., Dermatologica 169, 179 (1984); H. Neittaanmaki et al., ibid. 177, 98 (1988); in allergic rhinitis: T. G. Gibbs et al., J. Int. Med. Res. 16, 413 (1988). Review of pharmacology and therapeutic efficacy: R. N. Brogden, D. McTavish, Drugs 41, 927-940 (1991).

Cetirizine CAS Registry Number: 83881-51-0 西替利嗪

CAS Name: [2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid
Additional Names: [2-[4-(p-chloro-a-phenylbenzyl)-1-piperazinyl]ethoxy]acetic acid
Percent Composition: C 64.8...
Literature References: Nonsedating type histamine H1-receptor antagonist; major metabolite of hydroxyzine, q.v. Pharmacological activity resides primarily in the (R)-isomer. Prepn: E. Baltes et al., EP 58146; eidem, US 4525358 (1982, 1985 both to UCB); of enantiomers: E. Cossement et al., GB 2225321 (1989 to UCB). See also: eidem, US 5478941 (1995 to UCB). Enantioselective HPLC determn in urine: S. O. Choi et al., Arch. Pharmacal Res. 23, 178 (2000). Stereoselective binding study: M. Gillard et al., Mol. Pharmacol. 61, 391 (2002). Clinical pharmacokinetics: E. Baltes et al., Fundam. Clin. Pharmacol. 15, 269 (2001). Clinical comparison with enantiomers on cutaneous response: J. L. Devalia et al., Allergy 56, 50 (2001); on nasal response: D. Y. Wang et al., ibid. 339. Review of pharmacology and clinical experience in allergic disorders: J. M. Portnoy, C. Dinakar, Expert Opin. Pharmacother. 5, 125-135 (2004).